This is a preprint.

It has not yet been peer reviewed by a journal.

The National Library of Medicine is running a pilot to include preprints that result from research funded by NIH in PMC and PubMed.

[Preprint]. 2024 Aug 15:2024.08.13.24311922.

doi: 10.1101/2024.08.13.24311922.

Genomic analysis of intracranial and subcortical brain volumes yields polygenic scores accounting for variation across ancestries

Luis M García-Marín^{1

2}, Adrian I Campos^{1

3}, Santiago Diaz-Torres^{2

4}, Jill A Rabinowitz⁵, Zuriel Ceja^{1

2}, Brittany L Mitchell^{1

2}, Katrina L Grasby^{1

2}, Jackson G Thorp¹, Ingrid Agartz^{6

7

8}, Saud Alhusaini^{9

10}, David Ames^{11

12}, Philippe Amouyel^{13

14

15

16}, Ole A Andreassen^{6

17

18}, Konstantinos Arfanakis^{19

20}, Alejandro Arias Vasquez²¹, Nicola J Armstrong²², Lavinia Athanasiu^{6

23}, Mark E Bastin²⁴, Alexa S Beiser^{25

26}, David A Bennett^{19

27}, Joshua C Bis²⁸, Marco Pm Boks²⁹, Dorret I Boomsma³⁰, Henry Brodaty³¹, Rachel M Brouwer³², Jan K Buitelaar³³, Ralph Burkhardt^{34

35}, Wiepke Cahn^{36

37}, Vince D Calhoun³⁸, Owen T Carmichael³⁹, Mallar Chakravarty^{40

41}, Qiang Chen⁴², Christopher R K Ching⁴³, Sven Cichon^{44

45

46}, Benedicto Crespo-Facorro⁴⁷, Fabrice Crivello⁴⁸, Anders M Dale⁴⁹, George Davey Smith^{50

51}, Eco Jc de Geus⁵², Philip L De Jager⁵³, Greig I de Zubicaray⁵⁴, Stéphanie Debette^{54

55}, Charles DeCarli⁵⁶, Chantal Depondt⁵⁷, Sylvane Desrivières⁵⁸, Srdjan Djurovic^{59

60}, Stefan Ehrlich⁶¹, Susanne Erk⁶², Thomas Espeseth^{63

64}, Guillén Fernández⁶⁵, Irina Filippi⁶⁶, Simon E Fisher^{67

68}, Debra A Fleischman^{19

69}, Evan Fletcher⁷⁰, Myriam Fornage⁷¹, Andreas J Forstner^{44

72}, Clyde Francks^{65

67

73}, Barbara Franke^{33

74}, Tian Ge⁷⁵, Aaron L Goldman⁴², Hans J Grabe⁷⁶, Robert C Green⁷⁷, Oliver Grimm^{78

79}, Nynke A Groenewold⁸⁰, Oliver Gruber⁸¹, Vilmundur Gudnason^{82

83}, Asta K Håberg^{84

85}, Unn K Haukvik^{86

87}, Andreas Heinz⁸⁷, Derrek P Hibar⁸⁸, Saima Hilal⁸⁹, Jayandra J Himali^{25

26

90

91

92}, Beng-Choon Ho⁹³, David F Hoehn⁹⁴, Pieter J Hoekstra^{95

96}, Edith Hofer^{97

98}, Wolfgang Hoffmann^{99

100}, Avram J Holmes¹⁰¹, Georg Homuth¹⁰², Norbert Hosten¹⁰³, M Kamran Ikram¹⁰⁴, Jonathan C Ipser¹⁰⁵, Clifford R Jack Jr¹⁰⁶, Neda Jahanshad⁴³, Erik G Jönsson^{6

107}, Rene S Kahn³⁶, Ryota Kanai¹⁰⁸, Marieke Klein^{65

74}, Maria J Knol¹⁰⁹, Lenore J Launer¹¹⁰, Stephen M Lawrie¹¹¹, Stephanie Le Hellard⁶⁰, Phil H Lee^{112

113

114}, Hervé Lemaître¹¹⁵, Shuo Li^{25

26}, David Cm Liewald¹¹⁶, Honghuang Lin¹¹⁷, W T Longstreth Jr^{118

119}, Oscar L Lopez¹²⁰, Michelle Luciano¹²¹, Pauline Maillard⁷⁰, Andre F Marquand⁶⁵, Nicholas G Martin¹, Jean-Luc Martinot¹²², Karen A Mather³¹, Venkata S Mattay⁴², Katie L McMahon¹²³, Patrizia Mecocci^{124

125}, Ingrid Melle⁶, Andreas Meyer-Lindenberg¹²⁶, Nazanin Mirza-Schreiber^{127

128}, Yuri Milaneschi^{129

130

131

132}, Thomas H Mosley¹³³, Thomas W Mühleisen^{44

134

135}, Bertram Müller-Myhsok¹³⁶, Susana Muñoz Maniega²⁴, Matthias Nauck^{137

138}, Kwangsik Nho¹³⁹, Wiro J Niessen¹⁴⁰, Markus M Nöthen⁷², Paul A Nyquist^{141

142}, Jaap Oosterlaan^{143

144

145}, Massimo Pandolfo^{146

147}, Tomas Paus^{148

149}, Zdenka Pausova^{150

151}, Brenda Wjh Penninx¹²⁹, G Bruce Pike¹⁵², Bruce M Psaty^{28

119

153}, Benno Pütz¹⁵⁴, Simone Reppermund^{31

155}, Marcella D Rietschel¹⁵⁶, Shannon L Risacher^{157

158}, Nina Romanczuk-Seiferth^{159

160}, Rafael Romero-Garcia^{161

162}, Gennady V Roshchupkin^{109

163}, Jerome I Rotter¹⁶⁴, Perminder S Sachdev^{31

165}, Philipp G Sämann⁹⁴, Arvin Saremi⁴³, Muralidharan Sargurupremraj^{166

90}, Andrew J Saykin¹⁵⁷, Lianne Schmaal^{167

168}, Helena Schmidt¹⁶⁹, Reinhold Schmidt¹⁷⁰, Peter R Schofield^{171

172}, Markus Scholz^{35

173}, Gunter Schumann^{174

175}, Emanuel Schwarz¹²⁶, Li Shen¹⁷⁶, Jean Shin¹⁷⁷, Sanjay M Sisodiya^{178

179}, Albert V Smith^{82

180}, Jordan W Smoller⁷⁵, Hilkka S Soininen¹⁸¹, Vidar M Steen^{60

182}, Dan J Stein¹⁸³, Jason L Stein¹⁸⁴, Sophia I Thomopoulos⁴³, Arthur W Toga⁴³, Diana Tordesillas-Gutiérrez^{185

186}, Julian N Trollor^{31

187}, Maria C Valdes-Hernandez²⁴, Dennis van 't Ent¹⁸⁸, Hans van Bokhoven^{33

189}, Dennis van der Meer^{6

190}, Nic Ja van der Wee¹⁹¹, Javier Vázquez-Bourgon^{192

193

194}, Dick J Veltman¹²⁹, Meike W Vernooij^{109

163}, Arno Villringer^{195

196}, Louis N Vinke¹⁹⁷, Henry Völzke¹⁰⁰, Henrik Walter⁶², Joanna M Wardlaw^{24

198}, Daniel R Weinberger^{42

141

199

200

201}, Michael W Weiner^{202

203

204}, Wei Wen³¹, Lars T Westlye^{6

63}, Eric Westman²⁰⁵, Tonya White²⁰⁶, A Veronica Witte^{195

196}, Christiane Wolf⁹⁴, Jingyun Yang^{19

27}, Marcel P Zwiers³³, M Arfan Ikram¹⁰⁹, Sudha Seshadri^{26

90}, Paul M Thompson⁴³, Claudia L Satizabal^{26

207

208}, Sarah E Medland^{1

2

54

209}, Miguel E Rentería^{1

2}

Affiliations

¹ Brain & Mental Health Program, QIMR Berghofer Medical Research Institute, Brisbane, QLD, 4006, Australia.
² School of Biomedical Sciences, Faculty of Medicine, The University of Queensland, Brisbane, QLD, 4072, Australia.
³ Institute for Molecular Biosciences, The University of Queensland, Brisbane, QLD, 4072, Australia.
⁴ Population Health Program, QIMR Berghofer Medical Research Institute, Brisbane, QLD, 4006, Australia.
⁵ Department of Psychiatry, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ 08854, USA.
⁶ Centre for Precision Psychiatry, Institute of Clinical Medicine, University of Oslo, Oslo, 0319, Norway.
⁷ Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, 0407, Norway.
⁸ Department of Clinical Neuroscience, Karolinska Institutet & Stockholm Health Care Services, Stockholm, SE-11364, Sweden.
⁹ Department of Neurology, Alpert Medical School of Brown University, Providence, RI, 02903, USA.
¹⁰ Molecular & Cellular Therapeutics Department, Royal College of Surgeons in Ireland, Dublin, D15, Ireland.
¹¹ Academic Unit Psychiatry of Old Age, University of Melbourne, Kew, VIC, 3101, Australia.
¹² National Ageing Research Institute, Parkville, VIC, 3052, Australia.
¹³ Universite Lille, U1167 - RID-AGE - LabEx DISTALZ - Risk factors and molecular determinants of aging diseases, Lille, F-59000, France.
¹⁴ Institut National de la Sante et de la Recherche Medicale, U1167, Lille, F-59000, France.
¹⁵ Centre Hospitalier Universitaire de Lille, Department of Public Health, Lille, F-59000, Franch.
¹⁶ Institut Pasteur de Lille UMR1167, Lille, F-59000, France.
¹⁷ Division of Mental Health and Addiction, Oslo University Hospital, Oslo, 0407, Norway.
¹⁸ KG Jebsen Centre for Neurodevelopmental Disorders, University of Oslo, 0407, Norway.
¹⁹ Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, 60612, USA.
²⁰ Department of Biomedical Engineering, Illinois Institute of Technology, Chicago, 60616, USA.
²¹ Departments of Psychiatry and Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, 6525 GA, The Netherlands.
²² Department of Mathematics and Statistics, Curtin University, Perth, Australia.
²³ CoE NORMENT, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway, Oslo, 0455, Norway.
²⁴ Centre for Clinical Brain Sciences and Edinburgh Imaging, University of Edinburgh, Edinburgh, EH16 4SB, United Kingdom.
²⁵ Department of Biostatistics, School of Public Health, Boston University, Boston, MA, 02118, USA.
²⁶ Framingham Heart Study, Chobanian and Avedisian Boston University School of Medicine, Boston, MA, 02118, USA.
²⁷ Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, 60612, USA.
²⁸ Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, 98195-9458, USA.
²⁹ Brain Center University Medical Center Utrecht, Utrecht, 3508GA, The Netherlands.
³⁰ Vrije Universiteit, Amsterdam, 1081BT, The Netherlands.
³¹ Centre for Healthy Brain Ageing (CHeBA), Discipline of Psychiatry and Mental Health, School of Clinical Medicine, University of New South Wales, Sydney, NSW, 2052, Australia.
³² Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neurocience, VU Amsterdam, Amsterdam, 1081 HV, The Netherlands.
³³ Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, 6525 EN, The Netherlands.
³⁴ Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Regensburg, Regensburg University, Regensburg, 93053, Germany.
³⁵ LIFE Research Center for Civilization Diseases, University of Leipzig, Leipzig, 04103, Germany.
³⁶ Department of Psychiatry, University Medical Center Utrecht, Utrecht, 3584CX, The Netherlands.
³⁷ Altrecht Mental Health Institute, Utrecht, 3512PG, The Netherlands.
³⁸ Tri-institutional Center for Translational Research in Neuroimaging and Data Science (TReNDS), {Georgia State, Georgia Tech, Emory}, Atlanta, GA, 30303, USA.
³⁹ Pennington Biomedical Research Center, Baton Rouge, LA, 70808, USA.
⁴⁰ Cerebral Imaging Centre, Douglas Research Centre, Montreal, QC, H4H 1R3, Canada.
⁴¹ Department of Psychiatry, McGill University, Montreal, QC, H3A 1A1, Canada.
⁴² Lieber Institute for Brain Development, Baltimore, MD, 21205, USA.
⁴³ Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA, 90292, USA.
⁴⁴ Institute of Neuroscience and Medicine (INM-1), Research Center Jülich, Jülich, 52428, Germany.
⁴⁵ Department of Biomedicine, University of Basel, Basel, CH-4031, Switzerland.
⁴⁶ Medical Genetics, Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, 4031, Switzerland.
⁴⁷ HU Virgen del Rocio, Instituto de Investigacion biomedica IBIS-CSIC, Universidad de Sevilla, CIBERSAM, Sevilla, 41013, Spain.
⁴⁸ CNRS, IMN, UMR 5293, University of Bordeaux, Bordeaux, 33076, France.
⁴⁹ Center for Multimodal Imaging and Genetics, La Jolla, CA, 92093, USA.
⁵⁰ MRC Integrative Epidemiology Unit, University of Bristol, Bristol, BS8 2BN, United Kingdom.
⁵¹ Population Health Sciences, University of Bristol, Bristol, BS8 BN, United Kingdom.
⁵² Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, 1081 BT, The Netherlands.
⁵³ Center for Translational & Computational Neuroimmunology, Department of Neurology, Columbia University Irving Medical Center, New York, NY, 10538, USA.
⁵⁴ School of Psychology and Counselling, Queensland University of Technology, Brisbane, QLD, 4059, Australia.
⁵⁵ Department of Neurology, Institute of Neurodegenerative Diseases, Bordeaux University Hospital, Bordeaux, F-33000, France.
⁵⁶ Imaging of Dementia and Aging Laboratory, Department of Neurology, University of California, Davis, Sacramento, CA, 95817, USA.
⁵⁷ Department of Neurology, Hôpital Universitaire de Bruxelles, Université Libre de Bruxelles, Brussels, 1070, Belgium.
⁵⁸ Social, Genetic, and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, SE5 8AF, United Kingdom.
⁵⁹ Department of Medical Genetics, Oslo University Hospital, Oslo, 0450, Norway.
⁶⁰ Department of Clinical Science, University of Bergen, Bergen, 5021, Norway.
⁶¹ Translational Developmental Neuroscience Section, Division of Psychological and Social Medicine and Developmental Neurosciences, Faculty of Medicine, TU Dresden, Dresden, 01307, Germany.
⁶² Department of Psychiatry and Psychotherapy, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, 11017, Germany.
⁶³ Department of Psychology, University of Oslo, Oslo, 0373, Norway.
⁶⁴ Department of Psychology, Oslo New University College, Oslo, 0456, Norway.
⁶⁵ Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, 6500 HB, The Netherlands.
⁶⁶ INSERM U1299, Paris Saclay University, Gif-sur-Yvette, 91190, France.
⁶⁷ Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, 6525 XD, The Netherlands.
⁶⁸ Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, 6500 HE, The Netherlands.
⁶⁹ Department of Psychiatry and Behavioral Sciences, Rush University Medical Center, Chicago, IL, 60612, USA.
⁷⁰ Department of Neurology, University of California Davis, Davis, CA, 95616, USA.
⁷¹ Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, 77030, USA.
⁷² Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, 53127, Germany.
⁷³ Department of Cognitive Neuroscience, Radboud University Medical Center, Nijmegen, 6525 GA, The Netherlands.
⁷⁴ Department of Human Genetics, Radboud University Medical Center, Nijmegen, 6525 GA, The Netherlands.
⁷⁵ Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, 02114, USA.
⁷⁶ Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, 17475, Germany.
⁷⁷ Department of Medicine (Genetics), Mass General Brigham and Harvard Medical School, Boston, MA, 02115, USA.
⁷⁸ Central Institute of Mental Health, Mannheim, 68159, Germany.
⁷⁹ Goethe-University Frankfurt, Frankfurt am Main, 60528, Germany.
⁸⁰ Department of Psychiatry and Mental Health, Neuroscience Institute, University of Cape Town, Cape Town, 7925, South Africa.
⁸¹ Section for Experimental Psychopathology and Neuroimaging, Department of General Psychiatry, Heidelberg University, Heidelberg, D-69115, Germany.
⁸² Icelandic Heart Association, Kopavogur, 201, Iceland.
⁸³ Faculty of Medicine, University of Iceland, Reykjavik, 101, Iceland.
⁸⁴ Department of Neuromedicine and Movement, NTNU Science, Trondheim, 7030, Norway.
⁸⁵ MiDT National Research Center, Department of Research, St Olavs Hospital, Trondheim, 7006, Norway.
⁸⁶ Norwegian Centre for Mental Health Research (NORMENT), Department of Mental Health and Addiction, University of Oslo, Oslo, 0450, Norway.
⁸⁷ Centre for Forensic Psychiatry Research, Oslo University Hospital, Oslo, 0455, Norway.
⁸⁸ Product Development, Genentech, Inc., South San Francisco, CA, 94080, USA.
⁸⁹ Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, 117549, Singapore.
⁹⁰ Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, University of Texas Health Sciences Center, San Antonio, TX, 78229-3900, USA.
⁹¹ Department of Population Health Sciences, UT Health Science Center San Antonio, San Antonio, TX, 78229, USA.
⁹² Department of Neurology, Boston University School of Medicine, Boston, MA, 02118, USA.
⁹³ Department of Psychiatry, Carver College of Medicine, University of Iowa, Iowa City, IA, 52246, USA.
⁹⁴ Max Planck Institute of Psychiatry, Munich, 80804, Germany.
⁹⁵ Department of Child and Adolescent Psychiatry, University of Groningen, University Medical Center Groningen, Groningen, 9713 GZ, The Netherlands.
⁹⁶ Accare Child Study Center, Groningen, 9723 HE, The Netherlands.
⁹⁷ Division of Neurogeriatrics, Department of Neurology, Medical University of Graz, Graz, 8036, Austria.
⁹⁸ Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Graz, 8036, Austria.
⁹⁹ German Centre for Neurodegenerative Diseases (DZNE) - site Rostock/Greifswald, Greifswald, 17489, Germany.
¹⁰⁰ Institute for Community Medicine, University Medicine Greifswald, Greifswald, 17495, Germany.
¹⁰¹ Department of Psychiatry, Brain Health Institute, Rutgers University, Piscataway, NJ, 08854, USA.
¹⁰² Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, 17475, Germany.
¹⁰³ Department of Radiology, University Clinic Greifswald, Greifswald, 17475, Germany.
¹⁰⁴ Departments of Epidemiology and Neurology, Erasmus MC, Rotterdam, 3015 CN , The Netherlands.
¹⁰⁵ Department of Psychiatry and Mental Health, Neuroscience Institute, Groote Schuur Hospital, University of Cape Town, Cape Town, 7925, South Africa.
¹⁰⁶ Department of Radiology, Mayo Clinic, Rochester, MN, 55905, USA.
¹⁰⁷ Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet & Stockholm Health Care Sciences, Stockholm Region, Stockholm, SE-11364, Sweden.
¹⁰⁸ Araya, Inc., Tokyo, 101-0025, Japan.
¹⁰⁹ Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, 3015 GD, The Netherlands.
¹¹⁰ Intramural Research Program, National Institute on Aging, Baltimore, MD, 21224, USA.
¹¹¹ Division of Psychiatry, University of Edinburgh, Edinburgh, EH10 5HF, United Kingdom.
¹¹² Center for Genomic Medicine, Mass General Brigham, Boston, MA, 02114, USA.
¹¹³ Department of Psychiatry, Harvard Medical School, Boston, MA, 02115, USA.
¹¹⁴ Stanley Center for Psychiatry, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
¹¹⁵ Groupe d'Imagerie Neurofonctionnelle, Institut des Maladies Neurodégénératives, UMR 5293, CNRS, Université de Bordeaux, Bordeaux, 33076, France.
¹¹⁶ PPLS, University of Edinburgh, Edinburgh, EH8, United Kingdom.
¹¹⁷ Department of Medicine, University of Massachusetts Chan Medical School, Worcester, MA, 01655, USA.
¹¹⁸ Department of Neurology, University of Washington, Seattle, WA, 98104-2420, USA.
¹¹⁹ Department of Epidemiology, University of Washington, Seattle, WA, 98195-9458, USA.
¹²⁰ Departments of Neurology and Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15213, USA.
¹²¹ Department of Psychology, University of Edinburgh, Edinburgh, EH8 9JZ, United Kingdom.
¹²² Université Paris-Saclay; Institut National de la Santé et de la Recherche Médicale, INSERM U1299 "Trajectoires développementales Psychiatrie", Ecole Normale Supérieure Paris-Saclay, CNRS UMR 9010, Université Paris Cité, Centre Borelli, Gif sur Yvette, 911.
¹²³ School of Clinical Sciences, Queensland University of Technology, Brisbane, QLD, 4001, Australia.
¹²⁴ Institute of Gerontology and Geriatrics, Department of Medicine and Surgery, University of Perugia, Perugia, 06132, Italy.
¹²⁵ Clinical Geriatrics, NVS Department, Karolinska Institute, Huddinge, 14152, Sweden.
¹²⁶ Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, 68159, Germany.
¹²⁷ Institute of Neurogenomics,Helmholtz Munich, 85764, Neuherberg, Germany.
¹²⁸ Neurogenetic Systems Analysis Group, Institute of Neurogenomics, Helmholtz Munich, 85764, Neuherberg, Germany.
¹²⁹ Department of Psychiatry, Amsterdam UMC location Vrije Universiteit Amsterdam, Amsterdam, 1081 HJ, The Netherlands.
¹³⁰ Amsterdam Public Health, Mental Health program, Amsterdam, 1081 BT, The Netherlands.
¹³¹ Amsterdam Neuroscience, Mood, Anxiety, Psychosis, Sleep & Stress program, Amsterdam, 1081 BT, The Netherlands.
¹³² Amsterdam Neuroscience, Complex Trait Genetics program, Amsterdam, 1081 HV, The Netherlands.
¹³³ MIND Center, Jackson, MS, 39216, USA.
¹³⁴ Cécile and Oskar Vogt Institute for Brain Research, Medical Faculty, University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, D-40225, Germany.
¹³⁵ Department of Biomedicine, University Hospital Basel and University of Basel, Basel, CH-4031, Switzerland.
¹³⁶ Statistics Genetics Group, Max Planck Institute of Psychiatry, Munich, 80804, Germany.
¹³⁷ Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, 17489, Germany.
¹³⁸ German Centre for Cardiovascular Research (DZHK), Partner Site Greifswald, Greifswald, 17489, Germany.
¹³⁹ Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
¹⁴⁰ University Medical Center Groningen, Groningen, 9713GZ, The Netherlands.
¹⁴¹ Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, 21287, USA.
¹⁴² General internal Medicine, Johns Hopkins School of Medicine, Baltimore, MD, 21287, USA.
¹⁴³ Clinical Neuropsychology section, Vrije Universiteit Amsterdam, Amsterdam, 1081 BT, The Netherlands.
¹⁴⁴ Emma Children's Hospital, University Medical Centers Amsterdam, Amsterdam, 1100 DD, The Netherlands.
¹⁴⁵ Amsterdam Reproduction & Development Research Institute, Amsterdam, 1100 DD, The Netherlands.
¹⁴⁶ Université Libre de Bruxelles, Brussels, 1070, Belgium.
¹⁴⁷ Department of Neurology and Neurosurgery, McGill University, Montreal, QC, H3A 2B4, Canada.
¹⁴⁸ Departments of Psychiatry and Neuroscience, Faculty of Medicine, University of Montreal, Montreal, QC, H3T 1C5, Canada.
¹⁴⁹ Centre Hospitalier Universitaire Sainte-Justine, University of Montreal, Montreal, QC, H3T 1C5, Canada.
¹⁵⁰ Hospital for Sick Children, Toronto, ON, M5G 0A4, Canada.
¹⁵¹ Department of Physiology, University of Toronto, Toronto, M5G 0A4, Canada.
¹⁵² Departments of Radiology and Clinical Neurosciences, Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, T2N 4N1, Canada.
¹⁵³ Department of Health Systems and Population Health, Seattle, WA, 98195-9458, USA.
¹⁵⁴ Translational Psychiatry, Munich, 80804, Germany.
¹⁵⁵ Department of Developmental Disability Neuropsychiatry, Discipline of Psychiatry and Mental Health, School of Clinical Medicine, University of New South Wales, Sydney, NSW, 2052, Australia.
¹⁵⁶ Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Faculty of Medicine Mannheim, University of Heidelberg, Mannheim, 68159, Germany.
¹⁵⁷ Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
¹⁵⁸ Indiana Alzheimer's Disease Research Center, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
¹⁵⁹ Department of Psychiatry and Neuroscience, Charité - Universitätsmedizin Berlin, Berlin, 10117, Germany.
¹⁶⁰ Department of Psychology, Clinical Psychology and Psychotherapy, MSB Medical School Berlin, Berlin, 14197, Germany.
¹⁶¹ Instituto de Biomedicina de Sevilla (IBiS) HUVR/CSIC/Universidad de Sevilla/ CIBERSAM, ISCIII, Dpto. de Fisiología Médica y Biofísica, Sevilla, 41013, Spain.
¹⁶² Department of Psychiatry, University of Cambridge, Cambridge, CB2 0SZ, United Kingdom.
¹⁶³ Department of Radiology and Nuclear Medicine, Erasmus MC University Medical Center, Rotterdam, 3015 GD, The Netherlands.
¹⁶⁴ The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, 90502, USA.
¹⁶⁵ Neuropsychiatric Institute, The Prince of Wales Hospital, Randwick, NSW, 2031, Australia.
¹⁶⁶ INSERM U1219, Bordeaux Population Health Research Center, University of Bordeaux, Bordeaux, F-33000, France.
¹⁶⁷ Centre for Youth Mental Health, The University of Melbourne, Parkville, VIC, 3052, Australia.
¹⁶⁸ Orygen, Parkville, VIC, 3052, Australia.
¹⁶⁹ Institute of Molecular Biology & Biochemistry, Gottfried Schatz Center for Signaling, Metabolism & Aging, Medical University Graz, Graz, 8010, Austria.
¹⁷⁰ Department of Neurology, Medical University Graz Austria, Graz, 8023, Austria.
¹⁷¹ Neuroscience Research Australia, Sydney, NSW, 2031, Australia.
¹⁷² School of Biomedical Sciences, University of New South Wales, Sydney, NSW, 2052, Australia.
¹⁷³ Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, 04107, Germany.
¹⁷⁴ Centre for Population Neuroscience and Stratified Medicine (PONS), ISTBI, Fudan University, Shanghai, 200031, P.R. China.
¹⁷⁵ PONS Centre, Department of Psychiatry, CCM, Charite Unversitaetsmedizin Berlin, Berlin, 10017, Germany.
¹⁷⁶ Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
¹⁷⁷ The Hospital for Sick Children, Departments of Physiology and Nutritional Sciences, University of Toronto, Toronto, ON, M5G 0A4, Canada.
¹⁷⁸ Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, London, WC1N 3BG, United Kingdom.
¹⁷⁹ Chalfont Centre for Epilepsy, Chalfont St Peter, SL9 0RJ, United Kingdom.
¹⁸⁰ Department of Biostatistics, University of Michigan, Ann Arbor, MI, 48109, USA.
¹⁸¹ Department of Neurology, Institute of Clinical Mediciine, University of Eastern Finland, Kuopio, 70100, Finland.
¹⁸² Dr. Einar Martens Research Group for Biological Psychiatry, Department of Medical Genetics, Haukeland University Hospital, Bergen, N-5021, Norway.
¹⁸³ SAMRC Research Unit on Risk & Resilience in Mental Disorders, Department of Psychiatry & Neuroscience Institute, University of Cape Town, Cape Town, 7925, South Africa.
¹⁸⁴ Department of Genetics & UNC Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599-7250, USA.
¹⁸⁵ Instituto de Física de Cantabria (CSIC-UC), Santander, E-39005, Spain.
¹⁸⁶ Department of Radiology, Marqués de Valdecilla University Hospital, Valdecilla Biomedical Research Institute IDIVAL, Santander, 39011, Spain.
¹⁸⁷ The National Centre of Excellence in Intellectual Disability Health,, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW, 2052, Australia.
¹⁸⁸ Department of Biological Psychology & Netherlands Twin Register, Vrije Universiteit Amsterdam, Amsterdam, 1081 BT, The Netherlands.
¹⁸⁹ Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, 6525 GA, The Netherlands.
¹⁹⁰ School of Mental Health and Neuroscience, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, 6200MD, The Netherlands.
¹⁹¹ Department of Psychiatry, Leiden University Medical Center, Leiden, 2333 ZA, The Netherlands.
¹⁹² Department of Psychiatry, University Hospital Marqués de Valdecilla - IDIVAL, Santander, 39008, Spain.
¹⁹³ Departamento de Medicina y Psiquiatría, Universidad de Cantabria, Santander, 39008, Spain.
¹⁹⁴ Centro de Investigación Biomédica en Red en Salud Mental (CIBERSAM), Sevilla, 41013, Spain.
¹⁹⁵ Department of Neurology, Max Planck Institute for Human, Cognitive and Brain Sciences, Leipzig, 04103, Germany.
¹⁹⁶ Cognitive Neurology, University of Leipzig Medical Center, Leipzig, 04103, Germany.
¹⁹⁷ Department of Psychiatry, Massachusetts General Hospital, Boston, MA, 02114, USA.
¹⁹⁸ UK Dementia Research Institute Centre, University of Edinburgh, Edinburgh, EH16 4SB, United Kingdom.
¹⁹⁹ Department of Psychiatry, Johns Hopkins School of Medicine, Baltimore, MD, 21205, USA.
²⁰⁰ Department of Neuroscience, Johns Hopkins School of Medicine, Baltimore, MD, 21205, USA.
²⁰¹ Genetic Medicine, Johns Hopkins School of Medicine, Baltimore, MD, 21205, USA.
²⁰² University of California San Francisco, San Francisco, CA, 94121, USA.
²⁰³ Northern California Institute for Research & Education (NCIRE), San Francisco, CA, 94121, USA.
²⁰⁴ Veterans Administration Medical Center, San Francisco, CA, 94121, USA.
²⁰⁵ Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society (NVS), Karolinska Institutet, Huddinge, 14183, Sweden.
²⁰⁶ Section on Social and Cognitive Developmental Neuroscience, National Institute of Mental Health, Bethesda, MD, 20892-1276, USA.
²⁰⁷ Department of Population Health Sciences and Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, UT Health San Antonio, San Antonio, TX, 78229, USA.
²⁰⁸ Department of Neurology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, 02118, USA.
²⁰⁹ School of Psychology, The University of Queensland, Brisbane, QLD, 4072, Australia.

PMID: 39371125
PMCID: PMC11451674
DOI: 10.1101/2024.08.13.24311922

Genomic analysis of intracranial and subcortical brain volumes yields polygenic scores accounting for variation across ancestries

Luis M García-Marín et al. medRxiv. 2024.

[Preprint]. 2024 Aug 15:2024.08.13.24311922.

doi: 10.1101/2024.08.13.24311922.

Authors

Affiliations

¹ Brain & Mental Health Program, QIMR Berghofer Medical Research Institute, Brisbane, QLD, 4006, Australia.
² School of Biomedical Sciences, Faculty of Medicine, The University of Queensland, Brisbane, QLD, 4072, Australia.
³ Institute for Molecular Biosciences, The University of Queensland, Brisbane, QLD, 4072, Australia.
⁴ Population Health Program, QIMR Berghofer Medical Research Institute, Brisbane, QLD, 4006, Australia.
⁵ Department of Psychiatry, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ 08854, USA.
⁶ Centre for Precision Psychiatry, Institute of Clinical Medicine, University of Oslo, Oslo, 0319, Norway.
⁷ Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, 0407, Norway.
⁸ Department of Clinical Neuroscience, Karolinska Institutet & Stockholm Health Care Services, Stockholm, SE-11364, Sweden.
⁹ Department of Neurology, Alpert Medical School of Brown University, Providence, RI, 02903, USA.
¹⁰ Molecular & Cellular Therapeutics Department, Royal College of Surgeons in Ireland, Dublin, D15, Ireland.
¹¹ Academic Unit Psychiatry of Old Age, University of Melbourne, Kew, VIC, 3101, Australia.
¹² National Ageing Research Institute, Parkville, VIC, 3052, Australia.
¹³ Universite Lille, U1167 - RID-AGE - LabEx DISTALZ - Risk factors and molecular determinants of aging diseases, Lille, F-59000, France.
¹⁴ Institut National de la Sante et de la Recherche Medicale, U1167, Lille, F-59000, France.
¹⁵ Centre Hospitalier Universitaire de Lille, Department of Public Health, Lille, F-59000, Franch.
¹⁶ Institut Pasteur de Lille UMR1167, Lille, F-59000, France.
¹⁷ Division of Mental Health and Addiction, Oslo University Hospital, Oslo, 0407, Norway.
¹⁸ KG Jebsen Centre for Neurodevelopmental Disorders, University of Oslo, 0407, Norway.
¹⁹ Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, 60612, USA.
²⁰ Department of Biomedical Engineering, Illinois Institute of Technology, Chicago, 60616, USA.
²¹ Departments of Psychiatry and Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, 6525 GA, The Netherlands.
²² Department of Mathematics and Statistics, Curtin University, Perth, Australia.
²³ CoE NORMENT, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway, Oslo, 0455, Norway.
²⁴ Centre for Clinical Brain Sciences and Edinburgh Imaging, University of Edinburgh, Edinburgh, EH16 4SB, United Kingdom.
²⁵ Department of Biostatistics, School of Public Health, Boston University, Boston, MA, 02118, USA.
²⁶ Framingham Heart Study, Chobanian and Avedisian Boston University School of Medicine, Boston, MA, 02118, USA.
²⁷ Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, 60612, USA.
²⁸ Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, 98195-9458, USA.
²⁹ Brain Center University Medical Center Utrecht, Utrecht, 3508GA, The Netherlands.
³⁰ Vrije Universiteit, Amsterdam, 1081BT, The Netherlands.
³¹ Centre for Healthy Brain Ageing (CHeBA), Discipline of Psychiatry and Mental Health, School of Clinical Medicine, University of New South Wales, Sydney, NSW, 2052, Australia.
³² Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neurocience, VU Amsterdam, Amsterdam, 1081 HV, The Netherlands.
³³ Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, 6525 EN, The Netherlands.
³⁴ Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Regensburg, Regensburg University, Regensburg, 93053, Germany.
³⁵ LIFE Research Center for Civilization Diseases, University of Leipzig, Leipzig, 04103, Germany.
³⁶ Department of Psychiatry, University Medical Center Utrecht, Utrecht, 3584CX, The Netherlands.
³⁷ Altrecht Mental Health Institute, Utrecht, 3512PG, The Netherlands.
³⁸ Tri-institutional Center for Translational Research in Neuroimaging and Data Science (TReNDS), {Georgia State, Georgia Tech, Emory}, Atlanta, GA, 30303, USA.
³⁹ Pennington Biomedical Research Center, Baton Rouge, LA, 70808, USA.
⁴⁰ Cerebral Imaging Centre, Douglas Research Centre, Montreal, QC, H4H 1R3, Canada.
⁴¹ Department of Psychiatry, McGill University, Montreal, QC, H3A 1A1, Canada.
⁴² Lieber Institute for Brain Development, Baltimore, MD, 21205, USA.
⁴³ Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA, 90292, USA.
⁴⁴ Institute of Neuroscience and Medicine (INM-1), Research Center Jülich, Jülich, 52428, Germany.
⁴⁵ Department of Biomedicine, University of Basel, Basel, CH-4031, Switzerland.
⁴⁶ Medical Genetics, Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, 4031, Switzerland.
⁴⁷ HU Virgen del Rocio, Instituto de Investigacion biomedica IBIS-CSIC, Universidad de Sevilla, CIBERSAM, Sevilla, 41013, Spain.
⁴⁸ CNRS, IMN, UMR 5293, University of Bordeaux, Bordeaux, 33076, France.
⁴⁹ Center for Multimodal Imaging and Genetics, La Jolla, CA, 92093, USA.
⁵⁰ MRC Integrative Epidemiology Unit, University of Bristol, Bristol, BS8 2BN, United Kingdom.
⁵¹ Population Health Sciences, University of Bristol, Bristol, BS8 BN, United Kingdom.
⁵² Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, 1081 BT, The Netherlands.
⁵³ Center for Translational & Computational Neuroimmunology, Department of Neurology, Columbia University Irving Medical Center, New York, NY, 10538, USA.
⁵⁴ School of Psychology and Counselling, Queensland University of Technology, Brisbane, QLD, 4059, Australia.
⁵⁵ Department of Neurology, Institute of Neurodegenerative Diseases, Bordeaux University Hospital, Bordeaux, F-33000, France.
⁵⁶ Imaging of Dementia and Aging Laboratory, Department of Neurology, University of California, Davis, Sacramento, CA, 95817, USA.
⁵⁷ Department of Neurology, Hôpital Universitaire de Bruxelles, Université Libre de Bruxelles, Brussels, 1070, Belgium.
⁵⁸ Social, Genetic, and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, SE5 8AF, United Kingdom.
⁵⁹ Department of Medical Genetics, Oslo University Hospital, Oslo, 0450, Norway.
⁶⁰ Department of Clinical Science, University of Bergen, Bergen, 5021, Norway.
⁶¹ Translational Developmental Neuroscience Section, Division of Psychological and Social Medicine and Developmental Neurosciences, Faculty of Medicine, TU Dresden, Dresden, 01307, Germany.
⁶² Department of Psychiatry and Psychotherapy, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, 11017, Germany.
⁶³ Department of Psychology, University of Oslo, Oslo, 0373, Norway.
⁶⁴ Department of Psychology, Oslo New University College, Oslo, 0456, Norway.
⁶⁵ Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, 6500 HB, The Netherlands.
⁶⁶ INSERM U1299, Paris Saclay University, Gif-sur-Yvette, 91190, France.
⁶⁷ Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, 6525 XD, The Netherlands.
⁶⁸ Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, 6500 HE, The Netherlands.
⁶⁹ Department of Psychiatry and Behavioral Sciences, Rush University Medical Center, Chicago, IL, 60612, USA.
⁷⁰ Department of Neurology, University of California Davis, Davis, CA, 95616, USA.
⁷¹ Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, 77030, USA.
⁷² Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, 53127, Germany.
⁷³ Department of Cognitive Neuroscience, Radboud University Medical Center, Nijmegen, 6525 GA, The Netherlands.
⁷⁴ Department of Human Genetics, Radboud University Medical Center, Nijmegen, 6525 GA, The Netherlands.
⁷⁵ Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, 02114, USA.
⁷⁶ Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, 17475, Germany.
⁷⁷ Department of Medicine (Genetics), Mass General Brigham and Harvard Medical School, Boston, MA, 02115, USA.
⁷⁸ Central Institute of Mental Health, Mannheim, 68159, Germany.
⁷⁹ Goethe-University Frankfurt, Frankfurt am Main, 60528, Germany.
⁸⁰ Department of Psychiatry and Mental Health, Neuroscience Institute, University of Cape Town, Cape Town, 7925, South Africa.
⁸¹ Section for Experimental Psychopathology and Neuroimaging, Department of General Psychiatry, Heidelberg University, Heidelberg, D-69115, Germany.
⁸² Icelandic Heart Association, Kopavogur, 201, Iceland.
⁸³ Faculty of Medicine, University of Iceland, Reykjavik, 101, Iceland.
⁸⁴ Department of Neuromedicine and Movement, NTNU Science, Trondheim, 7030, Norway.
⁸⁵ MiDT National Research Center, Department of Research, St Olavs Hospital, Trondheim, 7006, Norway.
⁸⁶ Norwegian Centre for Mental Health Research (NORMENT), Department of Mental Health and Addiction, University of Oslo, Oslo, 0450, Norway.
⁸⁷ Centre for Forensic Psychiatry Research, Oslo University Hospital, Oslo, 0455, Norway.
⁸⁸ Product Development, Genentech, Inc., South San Francisco, CA, 94080, USA.
⁸⁹ Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, 117549, Singapore.
⁹⁰ Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, University of Texas Health Sciences Center, San Antonio, TX, 78229-3900, USA.
⁹¹ Department of Population Health Sciences, UT Health Science Center San Antonio, San Antonio, TX, 78229, USA.
⁹² Department of Neurology, Boston University School of Medicine, Boston, MA, 02118, USA.
⁹³ Department of Psychiatry, Carver College of Medicine, University of Iowa, Iowa City, IA, 52246, USA.
⁹⁴ Max Planck Institute of Psychiatry, Munich, 80804, Germany.
⁹⁵ Department of Child and Adolescent Psychiatry, University of Groningen, University Medical Center Groningen, Groningen, 9713 GZ, The Netherlands.
⁹⁶ Accare Child Study Center, Groningen, 9723 HE, The Netherlands.
⁹⁷ Division of Neurogeriatrics, Department of Neurology, Medical University of Graz, Graz, 8036, Austria.
⁹⁸ Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Graz, 8036, Austria.
⁹⁹ German Centre for Neurodegenerative Diseases (DZNE) - site Rostock/Greifswald, Greifswald, 17489, Germany.
¹⁰⁰ Institute for Community Medicine, University Medicine Greifswald, Greifswald, 17495, Germany.
¹⁰¹ Department of Psychiatry, Brain Health Institute, Rutgers University, Piscataway, NJ, 08854, USA.
¹⁰² Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, 17475, Germany.
¹⁰³ Department of Radiology, University Clinic Greifswald, Greifswald, 17475, Germany.
¹⁰⁴ Departments of Epidemiology and Neurology, Erasmus MC, Rotterdam, 3015 CN , The Netherlands.
¹⁰⁵ Department of Psychiatry and Mental Health, Neuroscience Institute, Groote Schuur Hospital, University of Cape Town, Cape Town, 7925, South Africa.
¹⁰⁶ Department of Radiology, Mayo Clinic, Rochester, MN, 55905, USA.
¹⁰⁷ Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet & Stockholm Health Care Sciences, Stockholm Region, Stockholm, SE-11364, Sweden.
¹⁰⁸ Araya, Inc., Tokyo, 101-0025, Japan.
¹⁰⁹ Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, 3015 GD, The Netherlands.
¹¹⁰ Intramural Research Program, National Institute on Aging, Baltimore, MD, 21224, USA.
¹¹¹ Division of Psychiatry, University of Edinburgh, Edinburgh, EH10 5HF, United Kingdom.
¹¹² Center for Genomic Medicine, Mass General Brigham, Boston, MA, 02114, USA.
¹¹³ Department of Psychiatry, Harvard Medical School, Boston, MA, 02115, USA.
¹¹⁴ Stanley Center for Psychiatry, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
¹¹⁵ Groupe d'Imagerie Neurofonctionnelle, Institut des Maladies Neurodégénératives, UMR 5293, CNRS, Université de Bordeaux, Bordeaux, 33076, France.
¹¹⁶ PPLS, University of Edinburgh, Edinburgh, EH8, United Kingdom.
¹¹⁷ Department of Medicine, University of Massachusetts Chan Medical School, Worcester, MA, 01655, USA.
¹¹⁸ Department of Neurology, University of Washington, Seattle, WA, 98104-2420, USA.
¹¹⁹ Department of Epidemiology, University of Washington, Seattle, WA, 98195-9458, USA.
¹²⁰ Departments of Neurology and Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15213, USA.
¹²¹ Department of Psychology, University of Edinburgh, Edinburgh, EH8 9JZ, United Kingdom.
¹²² Université Paris-Saclay; Institut National de la Santé et de la Recherche Médicale, INSERM U1299 "Trajectoires développementales Psychiatrie", Ecole Normale Supérieure Paris-Saclay, CNRS UMR 9010, Université Paris Cité, Centre Borelli, Gif sur Yvette, 911.
¹²³ School of Clinical Sciences, Queensland University of Technology, Brisbane, QLD, 4001, Australia.
¹²⁴ Institute of Gerontology and Geriatrics, Department of Medicine and Surgery, University of Perugia, Perugia, 06132, Italy.
¹²⁵ Clinical Geriatrics, NVS Department, Karolinska Institute, Huddinge, 14152, Sweden.
¹²⁶ Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, 68159, Germany.
¹²⁷ Institute of Neurogenomics,Helmholtz Munich, 85764, Neuherberg, Germany.
¹²⁸ Neurogenetic Systems Analysis Group, Institute of Neurogenomics, Helmholtz Munich, 85764, Neuherberg, Germany.
¹²⁹ Department of Psychiatry, Amsterdam UMC location Vrije Universiteit Amsterdam, Amsterdam, 1081 HJ, The Netherlands.
¹³⁰ Amsterdam Public Health, Mental Health program, Amsterdam, 1081 BT, The Netherlands.
¹³¹ Amsterdam Neuroscience, Mood, Anxiety, Psychosis, Sleep & Stress program, Amsterdam, 1081 BT, The Netherlands.
¹³² Amsterdam Neuroscience, Complex Trait Genetics program, Amsterdam, 1081 HV, The Netherlands.
¹³³ MIND Center, Jackson, MS, 39216, USA.
¹³⁴ Cécile and Oskar Vogt Institute for Brain Research, Medical Faculty, University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, D-40225, Germany.
¹³⁵ Department of Biomedicine, University Hospital Basel and University of Basel, Basel, CH-4031, Switzerland.
¹³⁶ Statistics Genetics Group, Max Planck Institute of Psychiatry, Munich, 80804, Germany.
¹³⁷ Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, 17489, Germany.
¹³⁸ German Centre for Cardiovascular Research (DZHK), Partner Site Greifswald, Greifswald, 17489, Germany.
¹³⁹ Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
¹⁴⁰ University Medical Center Groningen, Groningen, 9713GZ, The Netherlands.
¹⁴¹ Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, 21287, USA.
¹⁴² General internal Medicine, Johns Hopkins School of Medicine, Baltimore, MD, 21287, USA.
¹⁴³ Clinical Neuropsychology section, Vrije Universiteit Amsterdam, Amsterdam, 1081 BT, The Netherlands.
¹⁴⁴ Emma Children's Hospital, University Medical Centers Amsterdam, Amsterdam, 1100 DD, The Netherlands.
¹⁴⁵ Amsterdam Reproduction & Development Research Institute, Amsterdam, 1100 DD, The Netherlands.
¹⁴⁶ Université Libre de Bruxelles, Brussels, 1070, Belgium.
¹⁴⁷ Department of Neurology and Neurosurgery, McGill University, Montreal, QC, H3A 2B4, Canada.
¹⁴⁸ Departments of Psychiatry and Neuroscience, Faculty of Medicine, University of Montreal, Montreal, QC, H3T 1C5, Canada.
¹⁴⁹ Centre Hospitalier Universitaire Sainte-Justine, University of Montreal, Montreal, QC, H3T 1C5, Canada.
¹⁵⁰ Hospital for Sick Children, Toronto, ON, M5G 0A4, Canada.
¹⁵¹ Department of Physiology, University of Toronto, Toronto, M5G 0A4, Canada.
¹⁵² Departments of Radiology and Clinical Neurosciences, Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, T2N 4N1, Canada.
¹⁵³ Department of Health Systems and Population Health, Seattle, WA, 98195-9458, USA.
¹⁵⁴ Translational Psychiatry, Munich, 80804, Germany.
¹⁵⁵ Department of Developmental Disability Neuropsychiatry, Discipline of Psychiatry and Mental Health, School of Clinical Medicine, University of New South Wales, Sydney, NSW, 2052, Australia.
¹⁵⁶ Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Faculty of Medicine Mannheim, University of Heidelberg, Mannheim, 68159, Germany.
¹⁵⁷ Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
¹⁵⁸ Indiana Alzheimer's Disease Research Center, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
¹⁵⁹ Department of Psychiatry and Neuroscience, Charité - Universitätsmedizin Berlin, Berlin, 10117, Germany.
¹⁶⁰ Department of Psychology, Clinical Psychology and Psychotherapy, MSB Medical School Berlin, Berlin, 14197, Germany.
¹⁶¹ Instituto de Biomedicina de Sevilla (IBiS) HUVR/CSIC/Universidad de Sevilla/ CIBERSAM, ISCIII, Dpto. de Fisiología Médica y Biofísica, Sevilla, 41013, Spain.
¹⁶² Department of Psychiatry, University of Cambridge, Cambridge, CB2 0SZ, United Kingdom.
¹⁶³ Department of Radiology and Nuclear Medicine, Erasmus MC University Medical Center, Rotterdam, 3015 GD, The Netherlands.
¹⁶⁴ The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, 90502, USA.
¹⁶⁵ Neuropsychiatric Institute, The Prince of Wales Hospital, Randwick, NSW, 2031, Australia.
¹⁶⁶ INSERM U1219, Bordeaux Population Health Research Center, University of Bordeaux, Bordeaux, F-33000, France.
¹⁶⁷ Centre for Youth Mental Health, The University of Melbourne, Parkville, VIC, 3052, Australia.
¹⁶⁸ Orygen, Parkville, VIC, 3052, Australia.
¹⁶⁹ Institute of Molecular Biology & Biochemistry, Gottfried Schatz Center for Signaling, Metabolism & Aging, Medical University Graz, Graz, 8010, Austria.
¹⁷⁰ Department of Neurology, Medical University Graz Austria, Graz, 8023, Austria.
¹⁷¹ Neuroscience Research Australia, Sydney, NSW, 2031, Australia.
¹⁷² School of Biomedical Sciences, University of New South Wales, Sydney, NSW, 2052, Australia.
¹⁷³ Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, 04107, Germany.
¹⁷⁴ Centre for Population Neuroscience and Stratified Medicine (PONS), ISTBI, Fudan University, Shanghai, 200031, P.R. China.
¹⁷⁵ PONS Centre, Department of Psychiatry, CCM, Charite Unversitaetsmedizin Berlin, Berlin, 10017, Germany.
¹⁷⁶ Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
¹⁷⁷ The Hospital for Sick Children, Departments of Physiology and Nutritional Sciences, University of Toronto, Toronto, ON, M5G 0A4, Canada.
¹⁷⁸ Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, London, WC1N 3BG, United Kingdom.
¹⁷⁹ Chalfont Centre for Epilepsy, Chalfont St Peter, SL9 0RJ, United Kingdom.
¹⁸⁰ Department of Biostatistics, University of Michigan, Ann Arbor, MI, 48109, USA.
¹⁸¹ Department of Neurology, Institute of Clinical Mediciine, University of Eastern Finland, Kuopio, 70100, Finland.
¹⁸² Dr. Einar Martens Research Group for Biological Psychiatry, Department of Medical Genetics, Haukeland University Hospital, Bergen, N-5021, Norway.
¹⁸³ SAMRC Research Unit on Risk & Resilience in Mental Disorders, Department of Psychiatry & Neuroscience Institute, University of Cape Town, Cape Town, 7925, South Africa.
¹⁸⁴ Department of Genetics & UNC Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599-7250, USA.
¹⁸⁵ Instituto de Física de Cantabria (CSIC-UC), Santander, E-39005, Spain.
¹⁸⁶ Department of Radiology, Marqués de Valdecilla University Hospital, Valdecilla Biomedical Research Institute IDIVAL, Santander, 39011, Spain.
¹⁸⁷ The National Centre of Excellence in Intellectual Disability Health,, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW, 2052, Australia.
¹⁸⁸ Department of Biological Psychology & Netherlands Twin Register, Vrije Universiteit Amsterdam, Amsterdam, 1081 BT, The Netherlands.
¹⁸⁹ Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, 6525 GA, The Netherlands.
¹⁹⁰ School of Mental Health and Neuroscience, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, 6200MD, The Netherlands.
¹⁹¹ Department of Psychiatry, Leiden University Medical Center, Leiden, 2333 ZA, The Netherlands.
¹⁹² Department of Psychiatry, University Hospital Marqués de Valdecilla - IDIVAL, Santander, 39008, Spain.
¹⁹³ Departamento de Medicina y Psiquiatría, Universidad de Cantabria, Santander, 39008, Spain.
¹⁹⁴ Centro de Investigación Biomédica en Red en Salud Mental (CIBERSAM), Sevilla, 41013, Spain.
¹⁹⁵ Department of Neurology, Max Planck Institute for Human, Cognitive and Brain Sciences, Leipzig, 04103, Germany.
¹⁹⁶ Cognitive Neurology, University of Leipzig Medical Center, Leipzig, 04103, Germany.
¹⁹⁷ Department of Psychiatry, Massachusetts General Hospital, Boston, MA, 02114, USA.
¹⁹⁸ UK Dementia Research Institute Centre, University of Edinburgh, Edinburgh, EH16 4SB, United Kingdom.
¹⁹⁹ Department of Psychiatry, Johns Hopkins School of Medicine, Baltimore, MD, 21205, USA.
²⁰⁰ Department of Neuroscience, Johns Hopkins School of Medicine, Baltimore, MD, 21205, USA.
²⁰¹ Genetic Medicine, Johns Hopkins School of Medicine, Baltimore, MD, 21205, USA.
²⁰² University of California San Francisco, San Francisco, CA, 94121, USA.
²⁰³ Northern California Institute for Research & Education (NCIRE), San Francisco, CA, 94121, USA.
²⁰⁴ Veterans Administration Medical Center, San Francisco, CA, 94121, USA.
²⁰⁵ Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society (NVS), Karolinska Institutet, Huddinge, 14183, Sweden.
²⁰⁶ Section on Social and Cognitive Developmental Neuroscience, National Institute of Mental Health, Bethesda, MD, 20892-1276, USA.
²⁰⁷ Department of Population Health Sciences and Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, UT Health San Antonio, San Antonio, TX, 78229, USA.
²⁰⁸ Department of Neurology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, 02118, USA.
²⁰⁹ School of Psychology, The University of Queensland, Brisbane, QLD, 4072, Australia.

PMID: 39371125
PMCID: PMC11451674
DOI: 10.1101/2024.08.13.24311922

Update in

Genomic analysis of intracranial and subcortical brain volumes yields polygenic scores accounting for variation across ancestries.
García-Marín LM, Campos AI, Diaz-Torres S, Rabinowitz JA, Ceja Z, Mitchell BL, Grasby KL, Thorp JG, Agartz I, Alhusaini S, Ames D, Amouyel P, Andreassen OA, Arfanakis K, Arias-Vasquez A, Armstrong NJ, Athanasiu L, Bastin ME, Beiser AS, Bennett DA, Bis JC, Boks MPM, Boomsma DI, Brodaty H, Brouwer RM, Buitelaar JK, Burkhardt R, Cahn W, Calhoun VD, Carmichael OT, Chakravarty M, Chen Q, Ching CRK, Cichon S, Crespo-Facorro B, Crivello F, Dale AM, Smith GD, de Geus EJC, De Jager PL, de Zubicaray GI, Debette S, DeCarli C, Depondt C, Desrivières S, Djurovic S, Ehrlich S, Erk S, Espeseth T, Fernández G, Filippi I, Fisher SE, Fleischman DA, Fletcher E, Fornage M, Forstner AJ, Francks C, Franke B, Ge T, Goldman AL, Grabe HJ, Green RC, Grimm O, Groenewold NA, Gruber O, Gudnason V, Håberg AK, Haukvik UK, Heinz A, Hibar DP, Hilal S, Himali JJ, Ho BC, Hoehn DF, Hoekstra PJ, Hofer E, Hoffmann W, Holmes AJ, Homuth G, Hosten N, Ikram MK, Ipser JC, Jack CR Jr, Jahanshad N, Jönsson EG, Kahn RS, Kanai R, Klein M, Knol MJ, Launer LJ, Lawrie SM, Hellard SL, Lee PH, Lemaître H, Li S, Liewald DCM, Lin H, Longstreth WT Jr, Lopez OL, Luciano M, Maillard P, Marquand AF, Martin NG, Martinot JL, Mather KA, Mat… See abstract for full author list ➔ García-Marín LM, et al. Nat Genet. 2024 Nov;56(11):2333-2344. doi: 10.1038/s41588-024-01951-z. Epub 2024 Oct 21. Nat Genet. 2024. PMID: 39433889 Free PMC article.

Abstract

Subcortical brain structures are involved in developmental, psychiatric and neurological disorders. We performed GWAS meta-analyses of intracranial and nine subcortical brain volumes (brainstem, caudate nucleus, putamen, hippocampus, globus pallidus, thalamus, nucleus accumbens, amygdala and, for the first time, the ventral diencephalon) in 74,898 participants of European ancestry. We identified 254 independent loci associated with these brain volumes, explaining up to 35% of phenotypic variance. We observed gene expression in specific neural cell types across differentiation time points, including genes involved in intracellular signalling and brain ageing-related processes. Polygenic scores for brain volumes showed predictive ability when applied to individuals of diverse ancestries. We observed causal genetic effects of brain volumes with Parkinson's disease and ADHD. Findings implicate specific gene expression patterns in brain development and genetic variants in comorbid neuropsychiatric disorders, which could point to a brain substrate and region of action for risk genes implicated in brain diseases.

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Conflict of interest statement

IA received speaker’s honorarium Lundbeck; OAA is a consultant to Cortechs.ai and Precision Health, speaker’s honorarium from Lundbeck, Janssen, Otsuka, Sunovion; HB is an Advisory Board Member or Consultant to Biogen, Eisai, Eli Lilly, Roche, Skin2Neuron, Cranbrook Care and Montefiore Homes; CRKC has received past partial research support from Biogen, Inc. (Boston, USA) for work unrelated to the topic of this manuscript; AMD is the Principal Investigator of a research agreement between General Electric Healthcare and the University of California, San Diego (UCSD); he is a Founder of and hold equity in CorTechs Labs, Inc. I am a member of the Scientific Advisory Board of Human Longevity, Inc., and the Mohn Medical Imaging and Visualization Center in Bergen, Norway. The terms of these arrangements have been reviewed and approved by UCSD in accordance with its conflict-of-interest policies; BF has received educational speaking fees from Medice; HJG has received travel grants and speakers honoraria from Fresenius Medical Care, Neuraxpharm, Servier and Janssen Cilag as well as research funding from Fresenius Medical Care; DPH is a full time employee of Genentech, Inc; NH is a shareholder various manufacturers of medical technology; AM-L has received consultant fees from Daimler und Benz Stiftung, EPFL Brain Mind Institute, Fondation FondaMental, Hector Stiftung II, Invisio, Janssen-Cilag GmbH, Lundbeck A/S, Lundbeckfonden, Lundbeck Int. Neuroscience Foundation, Neurotorium, MedinCell, The LOOP Zürich, University Medical Center Utrecht, University of Washington, Verein für Mentales Wohlbefinden, von Behring-Röntgen-Stiftung; speaker fees from Ärztekammer Nordrhein, Caritas, Clarivate, Dt. Gesellschaft für Neurowissenschaftliche Begutachtung, Gentner Verlag, Landesärztekammer Baden-Württemberg, LWL Bochum, Northwell Health, Ruhr University Bochum, Penn State University, Society of Biological Psychiatry, University Prague, Vitos Klinik Rheingau and editorial and/or author fees fromAmerican Association for the Advancement of Science, ECNP, Servier Int., Thieme Verlag; WN is founder of Quantib BV and was scientific lead of Quantib BV until Jan 31, 2023; MMN has received fees for membership in an advisory board from HMG Systems Engineering GmbH (Fürth, Germany), for membership in the Medical-Scientific Editorial Office of the Deutsches Ärzteblatt, and for serving as a consultant for EVERIS Belgique SPRL in a project of the European Commission (REFORM/SC2020/029). MMN receives salary payments from Life & Brain GmbH and holds shares in Life & Brain GmbH. All these concerned activities outside the submitted work; BMP serves on the Steering Committee of the Yale Open Data Access Project funded by Johnson & Johnson; AJS receives support from multiple NIH grants (P30 AG010133, P30 AG072976, R01 AG019771, R01 AG057739, U19 AG024904, R01 LM013463, R01 AG068193, T32 AG071444, U01 AG068057, U01 AG072177, and U19 AG074879). He has also received support from Avid Radiopharmaceuticals, a subsidiary of Eli Lilly (in kind contribution of PET tracer precursor); Bayer Oncology (Scientific Advisory Board); Eisai (Scientific Advisory Board); Siemens Medical Solutions USA, Inc. (Dementia Advisory Board); NIH NHLBI (MESA Observational Study Monitoring Board); Springer-Nature Publishing (Editorial Office Support as Editor-in-Chief, Brain Imaging and Behavior); MSreceived funding from Pfizer Inc. for a project not related to this research; ES received speaker fees from bfd buchholz fachinformationsdienst gmbh; PMT receives partial research support from Biogen, Inc., for research unrelated to this manuscript; MWW serves on Editorial Boards for Alzheimer’s & Dementia, and the Journal for Prevention of Alzheimer’s disease. He has served on Advisory Boards for Acumen Pharmaceutical, Alzheon, Inc., Cerecin, Merck Sharp & Dohme Corp., and NC Registry for Brain Health. He also serves on the USC ACTC grant which receives funding from Eisai for the AHEAD study. MWW has provided consulting to Boxer Capital, LLC, Cerecin, Inc., Clario, Dementia Society of Japan, Eisai, Guidepoint, Health and Wellness Partners, Indiana University, LCN Consulting, Merck Sharp & Dohme Corp., NC Registry for Brain Health, Prova Education, T3D Therapeutics, University of Southern California (USC), and WebMD. MWW has acted as a speaker/lecturer for China Association for Alzheimer’s Disease (CAAD) and Taipei Medical University, as well as a speaker/lecturer with academic travel funding provided by: AD/PD Congress, Cleveland Clinic, CTAD Congress, Foundation of Learning; Health Society (Japan), INSPIRE Project; U. Toulouse, Japan Society for Dementia Research, and Korean Dementia Society, Merck Sharp & Dohme Corp., National Center for Geriatrics and Gerontology (NCGG; Japan), University of Southern California (USC). MWW holds stock options with Alzeca, Alzheon, Inc., ALZPath, Inc., and Anven. MWW received support for his research from the following funding sources: National Institutes of Health (NIH)/NINDS/National Institute on Aging (NIA), Department of Defense (DOD), California Department of Public Health (CDPH), University of Michigan, Siemens, Biogen, Hillblom Foundation, Alzheimer’s Association, Johnson & Johnson, Kevin and Connie Shanahan, GE, VUmc, Australian Catholic University (HBI-BHR), The Stroke Foundation, and the Veterans Administration; AIC is currently employed by the Regeneron Genetics Center, a wholly-owned subsidiary of Regeneron Pharmaceuticals, Inc., and may hold Regeneron stock or stock options. All other authors declare no competing interests.

Figures

**Figure 1.. Meta-analyses results overview.**
Phenogram illustrating loci associated with each of the brain volumes under study at the common genome-wide significance threshold (p-value < 5×10⁻⁸). ICV = Intracranial volume, A = Left Hemisphere interior, B = Left Hemisphere exterior, C = Right hemisphere interior, D = Right hemisphere exterior, E = Both hemispheres upper. The p-values referenced here correspond to a two-tailed Z-test test as implemented in MTAG.

**Figure 2.. Polygenic prediction in the ABCD cohort.**
Barplots show the variance explained by intracranial and subcortical brain volume polygenic scores using the *SBayesR* approach with a linear mixed effects model implemented in GCTA for the whole sample (N = 10,440), and individuals of European (N = 5,267), Non-European (N = 5,173), African-only (N = 1,833), and Asian-only (N = 152) ancestry. The p-value of the association is shown at the top of each bar; those with an asterisk (*) were significant after Bonferroni multiple testing correction [0.05 / 50 [total number of tests] = 1×10⁻³]. Non-European ancestry individuals include, but are not limited to, African-only and Asian-only ancestries as individuals with admixed ancestry were also included. P-values in this figure correspond to wald-tests (2-sided) derived from the linear mixed model results.

**Figure 3.. Genetic overlap with neuropsychiatric traits and disorders**
Heatmap depicting genetic correlations (rG) of intracranial and subcortical brain volumes with complex human phenotypes. *p-value < 0.05; **p-value significant after Bonferroni multiple testing correction (0.05 / 320 [total number of genetic correlation tests] = 1.56×10⁻⁴). Genetic correlations were estimated using LD score regression. P-values correspond to chi-squared tests with one degree of freedom as implemented in LD score regression.

**Figure 4.. Genetic structure of subcortical brain volumes**
Path diagram of a three-factor model estimated with genomic structural equation modelling. Blue rectangles represent the genetic component of each subcortical brain volume. Green circles represent latent factors. Standardised path coefficients are presented.

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Genomic analysis of intracranial and subcortical brain volumes yields polygenic scores accounting for variation across ancestries

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Genomic analysis of intracranial and subcortical brain volumes yields polygenic scores accounting for variation across ancestries

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