Meta-Analysis

. 2018 May 29;9(1):2098.

doi: 10.1038/s41467-018-04362-x.

Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function

Gail Davies¹, Max Lam², Sarah E Harris^{1

3}, Joey W Trampush^{4

5}, Michelle Luciano¹, W David Hill¹, Saskia P Hagenaars^{1

6}, Stuart J Ritchie¹, Riccardo E Marioni^{1

3}, Chloe Fawns-Ritchie¹, David C M Liewald¹, Judith A Okely¹, Ari V Ahola-Olli^{7

8}, Catriona L K Barnes⁹, Lars Bertram¹⁰, Joshua C Bis¹¹, Katherine E Burdick^{12

13

14}, Andrea Christoforou^{15

16}, Pamela DeRosse^{2

17}, Srdjan Djurovic^{15

18}, Thomas Espeseth^{19

20}, Stella Giakoumaki²¹, Sudheer Giddaluru^{15

16}, Daniel E Gustavson^{22

23}, Caroline Hayward^{24

25}, Edith Hofer^{26

27}, M Arfan Ikram^{28

29

30}, Robert Karlsson³¹, Emma Knowles³², Jari Lahti^{33

34}, Markus Leber³⁵, Shuo Li³⁶, Karen A Mather³⁷, Ingrid Melle^{15

19}, Derek Morris³⁸, Christopher Oldmeadow³⁹, Teemu Palviainen⁴⁰, Antony Payton⁴¹, Raha Pazoki⁴², Katja Petrovic²⁶, Chandra A Reynolds⁴³, Muralidharan Sargurupremraj⁴⁴, Markus Scholz^{45

46}, Jennifer A Smith^{47

48}, Albert V Smith^{49

50}, Natalie Terzikhan^{28

51}, Anbupalam Thalamuthu³⁷, Stella Trompet⁵², Sven J van der Lee²⁸, Erin B Ware⁴⁸, B Gwen Windham⁵³, Margaret J Wright^{54

55}, Jingyun Yang^{56

57}, Jin Yu¹⁷, David Ames^{58

59}, Najaf Amin²⁸, Philippe Amouyel⁶⁰, Ole A Andreassen^{19

61}, Nicola J Armstrong⁶², Amelia A Assareh³⁷, John R Attia⁶³, Deborah Attix^{64

65}, Dimitrios Avramopoulos^{66

67}, David A Bennett^{56

57}, Anne C Böhmer^{68

69}, Patricia A Boyle^{56

70}, Henry Brodaty^{37

71}, Harry Campbell⁹, Tyrone D Cannon⁷², Elizabeth T Cirulli⁷³, Eliza Congdon⁷⁴, Emily Drabant Conley⁷⁵, Janie Corley¹, Simon R Cox¹, Anders M Dale^{22

76

77

78}, Abbas Dehghan^{42

79}, Danielle Dick⁸⁰, Dwight Dickinson⁸¹, Johan G Eriksson^{82

83

84

85}, Evangelos Evangelou^{42

82}, Jessica D Faul⁴⁸, Ian Ford⁸⁶, Nelson A Freimer⁷⁴, He Gao⁴², Ina Giegling⁸⁷, Nathan A Gillespie⁸⁸, Scott D Gordon⁸⁹, Rebecca F Gottesman^{90

91}, Michael E Griswold⁹², Vilmundur Gudnason^{49

50}, Tamara B Harris⁹³, Annette M Hartmann⁸⁷, Alex Hatzimanolis^{94

95

96}, Gerardo Heiss⁹⁷, Elizabeth G Holliday⁶³, Peter K Joshi⁹, Mika Kähönen^{98

99

100}, Sharon L R Kardia⁴⁷, Ida Karlsson³¹, Luca Kleineidam^{101

102

103

104}, David S Knopman¹⁰⁵, Nicole A Kochan^{37

106}, Bettina Konte⁸⁷, John B Kwok^{107

108}, Stephanie Le Hellard^{15

16}, Teresa Lee^{37

106}, Terho Lehtimäki^{109

110}, Shu-Chen Li^{111

112}, Christina M Lill¹¹³, Tian Liu^{10

111}, Marisa Koini²⁶, Edythe London⁷⁴, Will T Longstreth Jr^{114

115}, Oscar L Lopez¹¹⁶, Anu Loukola⁴⁰, Tobias Luck^{46

117}, Astri J Lundervold^{118

119}, Anders Lundquist^{120

121}, Leo-Pekka Lyytikäinen^{109

110}, Nicholas G Martin⁸⁹, Grant W Montgomery^{89

122}, Alison D Murray^{25

123}, Anna C Need¹²⁴, Raymond Noordam⁵², Lars Nyberg^{120

125

126}, William Ollier¹²⁷, Goran Papenberg^{111

128}, Alison Pattie¹²⁹, Ozren Polasek^{130

131}, Russell A Poldrack¹³², Bruce M Psaty^{11

133

134}, Simone Reppermund^{37

135}, Steffi G Riedel-Heller¹¹⁷, Richard J Rose¹³⁶, Jerome I Rotter^{137

138}, Panos Roussos^{12

139

140}, Suvi P Rovio⁷, Yasaman Saba¹⁴¹, Fred W Sabb¹⁴², Perminder S Sachdev^{37

106}, Claudia L Satizabal^{143

144}, Matthias Schmid¹⁴⁵, Rodney J Scott⁶³, Matthew A Scult¹⁴⁶, Jeannette Simino⁹², P Eline Slagboom¹⁴⁷, Nikolaos Smyrnis^{94

95}, Aïcha Soumaré⁴⁴, Nikos C Stefanis^{94

95

96}, David J Stott¹⁴⁸, Richard E Straub¹⁴⁹, Kjetil Sundet^{19

20}, Adele M Taylor¹²⁹, Kent D Taylor^{137

138}, Ioanna Tzoulaki^{42

79

150}, Christophe Tzourio^{44

151}, André Uitterlinden^{28

152}, Veronique Vitart²⁴, Aristotle N Voineskos¹⁵³, Jaakko Kaprio^{40

82

154}, Michael Wagner^{103

104}, Holger Wagner¹⁰², Leonie Weinhold¹⁴⁵, K Hoyan Wen²⁸, Elisabeth Widen⁴⁰, Qiong Yang³⁶, Wei Zhao⁴⁷, Hieab H H Adams^{28

155}, Dan E Arking⁶⁷, Robert M Bilder⁷⁴, Panos Bitsios¹⁵⁶, Eric Boerwinkle^{157

158}, Ornit Chiba-Falek⁶⁴, Aiden Corvin¹⁵⁹, Philip L De Jager^{160

161}, Stéphanie Debette^{44

162}, Gary Donohoe³⁸, Paul Elliott^{42

79}, Annette L Fitzpatrick^{115

163}, Michael Gill¹⁵⁹, David C Glahn³², Sara Hägg³¹, Narelle K Hansell⁵⁴, Ahmad R Hariri¹⁴⁶, M Kamran Ikram^{28

30}, J Wouter Jukema¹⁶⁴, Eero Vuoksimaa^{40

154}, Matthew C Keller¹⁶⁵, William S Kremen^{22

23}, Lenore Launer⁹³, Ulman Lindenberger¹¹¹, Aarno Palotie^{40

166

167}, Nancy L Pedersen³¹, Neil Pendleton¹⁶⁸, David J Porteous^{1

3

25}, Katri Räikkönen³³, Olli T Raitakari^{7

169}, Alfredo Ramirez^{35

68

102}, Ivar Reinvang²⁰, Igor Rudan⁹, Dan Rujescu⁸⁷, Reinhold Schmidt²⁶, Helena Schmidt¹⁴¹, Peter W Schofield¹⁷⁰, Peter R Schofield^{171

172}, John M Starr^{1

173}, Vidar M Steen^{15

16}, Julian N Trollor^{37

135}, Steven T Turner¹⁷⁴, Cornelia M Van Duijn²⁸, Arno Villringer^{175

176}, Daniel R Weinberger¹⁴⁹, David R Weir⁴⁸, James F Wilson^{9

24}, Anil Malhotra^{17

177

178}, Andrew M McIntosh^{1

179}, Catharine R Gale^{1

180}, Sudha Seshadri^{142

143

181}, Thomas H Mosley Jr⁵³, Jan Bressler¹⁵⁷, Todd Lencz^{17

179}, Ian J Deary¹⁸²

Affiliations

¹ Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, School of Philosophy, Psychology and Language Sciences, The University of Edinburgh, Edinburgh, EH8 9JZ, UK.
² Institute of Mental Health, Singapore, 539747, Singapore.
³ Medical Genetics Section, Centre for Genomic & Experimental Medicine, MRC Institute of Genetics & Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, EH4 2XU, UK.
⁴ BrainWorkup, LLC, Los Angeles, 90033, CA, USA.
⁵ Department of Psychiatry and Behavioral Sciences, Keck School of Medicine, University of Southern California, Los Angeles, 90033, CA, USA.
⁶ Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, De Crespigny Park, Denmark Hill, London, SE5 8AF, UK.
⁷ Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, 20520, Finland.
⁸ Department of Internal Medicine, Satakunta Central Hospital, Pori, 28100, Finland.
⁹ Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Teviot Place, Edinburgh, EH8 9AG, Scotland.
¹⁰ Max Planck Institute for Molecular Genetics, Berlin, 14195, Germany.
¹¹ Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, 98101, Washington, USA.
¹² Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, 10029, NY, USA.
¹³ Mental Illness Research, Education, and Clinical Center (VISN 3), James J. Peters VA Medical Center, Bronx, 10468, NY, USA.
¹⁴ Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, 02115, MA, USA.
¹⁵ NORMENT, K.G. Jebsen Centre for Psychosis Research, Department of Clinical Science, University of Bergen, Bergen, 5021, Norway.
¹⁶ Dr. Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, 5020, Norway.
¹⁷ Center for Psychiatric Neuroscience, Feinstein Institute for Medical Research, Manhasset, 11030, NY, USA.
¹⁸ Department of Medical Genetics, Oslo University Hospital, University of Bergen, Oslo, 0424, Norway.
¹⁹ Department of Psychology, University of Oslo, Oslo, 0373, Norway.
²⁰ Division of Mental Health and Addiction, Oslo University Hospital, Oslo, 0315, Norway.
²¹ Department of Psychology, University of Crete, Crete, GR-74100, Greece.
²² Department of Psychiatry, University of California, San Diego, 92093, CA, USA.
²³ Center for Behavior Genetics of Aging, University of California, San Diego, 92093, CA, USA.
²⁴ Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, EH4 2XU, UK.
²⁵ Generation Scotland, Centre for Genomic and Experimental Medicine, University of Edinburgh, Edinburgh, EH4 2XU, UK.
²⁶ Department of Neurology, Clinical Division of Neurogeriatrics, Medical University of Graz, Graz, 8036, Austria.
²⁷ Institute of Medical Informatics Statistics and Documentation, Medical University of Graz, Graz, 8036, Austria.
²⁸ Department of Epidemiology, Erasmus University Medical Center, Rotterdam, 3015, The Netherlands.
²⁹ Department of Radiology and Nuclear Medicine, Erasmus University Medical Center, Rotterdam, 3015, The Netherlands.
³⁰ Department of Neurology, Erasmus University Medical Center, Rotterdam, xxxxxx, The Netherlands.
³¹ Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, SE-171 77, Sweden.
³² Department of Psychiatry, Yale University School of Medicine, New Haven, 06511, CT, USA.
³³ Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, 00014, Finland.
³⁴ Helsinki Collegium for Advanced Studies, University of Helsinki, Helsinki, 00014, Finland.
³⁵ Department of Psychiatry and Psychotherapy, University of Cologne, Cologne, D-50937, Germany.
³⁶ Department of Biostatistics, Boston University School of Public Health, Boston, 02118, MA, USA.
³⁷ Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, 2031, Australia.
³⁸ Neuroimaging, Cognition & Genomics (NICOG) Centre, School of Psychology and Discipline of Biochemistry, National University of Ireland Galway, Galway, H91 TK33, Ireland.
³⁹ Medical Research Institute and Faculty of Health, University of Newcastle, New South Wa0les, 2308, Australia.
⁴⁰ Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, FI-00014, Finland.
⁴¹ Centre for EpidemiologyDivision of Population Health, Health Services Research & Primary Care, The University of Manchester, Manchester, M13 9PL, UK.
⁴² Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, W2 1PG, UK.
⁴³ Department of Psychology, University of California Riverside, Riverside, 92521, CA, USA.
⁴⁴ University of Bordeaux, Bordeaux Population Health Research Center, INSERM UMR 1219, F-33000, Bordeaux, France.
⁴⁵ Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, 04107, Germany.
⁴⁶ LIFE-Leipzig Research Center for Civilization Diseases, University of Leipzig, Leipzig, 04107, Germany.
⁴⁷ Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, 48109, USA.
⁴⁸ Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI, 48104, USA.
⁴⁹ Icelandic Heart Association, Kopavogur, IS-201, Iceland.
⁵⁰ University of Iceland, Reykjavik, 101, Iceland.
⁵¹ Department of Respiratory Medicine, Ghent University Hospital, De Pintelaan 185, 9000, Ghent, Belgium.
⁵² Section of Gerontology and Geriatrics, Department of Internal Medicine, Leiden University Medical Center, Leiden, 2333, The Netherlands.
⁵³ Department of Medicine, Division of Geriatrics, University of Mississippi Medical Center, Jackson, 39216, MS, USA.
⁵⁴ Queensland Brain Institute, University of Queensland, Brisbane, 4072, Australia.
⁵⁵ Centre for Advanced Imaging, University of Queensland, Brisbane, 4072, Australia.
⁵⁶ Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, 60612, IL, USA.
⁵⁷ Department of Neurological Sciences, Rush University Medical Center, Chicago, 60612, IL, USA.
⁵⁸ National Ageing Research Institute, Royal Melbourne Hospital, Victoria, 3052, Australia.
⁵⁹ Academic Unit for Psychiatry of Old Age, University of Melbourne, St George's Hospital, Kew, 3010, Australia.
⁶⁰ Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1167-LabEx DISTALZ, F-59000, Lille, France.
⁶¹ Norwegian Centre for Mental Disorders Research (NORMENT), Institute of Clinical Medicine, University of Oslo, Oslo, 0372, Norway.
⁶² Mathematics and Statistics, Murdoch University, Perth, 6150, Australia.
⁶³ Hunter Medical Research Institute and Faculty of Health, University of Newcastle, New South Wales, 2305, Australia.
⁶⁴ Department of NeurologyBryan Alzheimer's Disease Research Center, and Center for Genomic and Computational Biology, Duke University Medical Center, Durham, 27708, NC, USA.
⁶⁵ Psychiatry and Behavioral Sciences, Division of Medical Psychology, and Department of Neurology, Duke University Medical Center, Durham, 27708, NC, USA.
⁶⁶ Department of Psychiatry, Johns Hopkins University School of Medicine, MD, Baltimore, 21287, USA.
⁶⁷ McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, MD, Baltimore, 21287, USA.
⁶⁸ Institute of Human Genetics, University of Bonn, Bonn, 53113, Germany.
⁶⁹ Department of Genomics, Life and Brain Center, University of Bonn, Bonn, 53113, Germany.
⁷⁰ Departments of Behavioral Sciences, Rush University Medical Center, Chicago, 60612, IL, USA.
⁷¹ Dementia Centre for Research Collaboration, University of New South Wales, Sydney, 2031, NSW, Australia.
⁷² Department of Psychology, Yale University, New Haven, 06520, CT, USA.
⁷³ Human Longevity Inc, Durham, 27709, NC, USA.
⁷⁴ UCLA Semel Institute for Neuroscience and Human Behavior, Los Angeles, 90024, CA, USA.
⁷⁵ 23andMe, Inc., Mountain View, 94041, CA, USA.
⁷⁶ Department of Cognitive Science, University of California, San Diego, La Jolla, 92093, CA, USA.
⁷⁷ Department of Neurosciences, University of California, San Diego, La Jolla, 92093, CA, USA.
⁷⁸ Department of Radiology, University of California, San Diego, La Jolla, 92093, CA, USA.
⁷⁹ MRC-PHE Centre for Environment, School of Public Health, Imperial College London, London, W2 1PG, UK.
⁸⁰ Department of Psychology, Virginia Commonwealth University, Richmond, 23284, VA, USA.
⁸¹ Clinical and Translational Neuroscience Branch, Intramural Research Program, National Institute of Mental Health, National Institute of Health, Bethesda, 20892, MD, USA.
⁸² National Institute for Health and Welfare, Helsinki, FI-00271, Finland.
⁸³ Department of General Practice and Primary Health Care, University of Helsinki, Helsinki, 00290, Finland.
⁸⁴ Helsinki University Central Hospital, Unit of General Practice, Helsinki, FI-00029, Finland.
⁸⁵ Folkhälsan Research Centre, Helsinki, 2018, Finland.
⁸⁶ Robertson Centre for Biostatistics, University of Glasgow, Glasgow, G12 8QQ, United Kingdom.
⁸⁷ Department of Psychiatry, Martin Luther University of Halle-Wittenberg, Halle, 06108, Germany.
⁸⁸ Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, 23298, VA, USA.
⁸⁹ QIMR Berghofer Medical Research Institute, Brisbane, 4029, Australia.
⁹⁰ Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, 21287, MD, USA.
⁹¹ Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, 21205, MD, USA.
⁹² Department of Data Science, University of Mississippi Medical Center, Jackson, 39216, MS, USA.
⁹³ Intramural Research Program National Institutes on Aging, National Institutes of Health, Bethesda, 20892, MD, USA.
⁹⁴ Department of Psychiatry, National and Kapodistrian University of Athens Medical School, Eginition Hospital, Athens, 11528, Greece.
⁹⁵ University Mental Health Research Institute, Athens, GR-156 01, Greece.
⁹⁶ Neurobiology Research Institute, Theodor-Theohari Cozzika Foundation, Athens, 11521, Greece.
⁹⁷ Department of Epidemiology, University of North Carolina Gillings School of Global Public Health, Chapel Hill, 27599, NC, USA.
⁹⁸ Department of Clinical Physiology, Tampere University Hospital, and Finnish Cardiovascular Research Center, Tampere, FI-33014, Finland.
⁹⁹ Faculty of Medicine and Life Sciences, University of Tampere, Tampere, 33521, Finland.
¹⁰⁰ Department of Clinical Physiology, Finnish Cardiovascular Research Center-Tampere, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, 33014, Finland.
¹⁰¹ Department of Psychiatry Medical Faculty, University of Cologne, Cologne, 50923, Germany.
¹⁰² Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, 53127, Germany.
¹⁰³ German Center for Neurodegenerative Diseases (DZNE), Bonn, 53127, Germany.
¹⁰⁴ Department for Neurodegenerative Diseases and Geriatric Psychiatry, University of Bonn, Bonn, 53127, Germany.
¹⁰⁵ Department of Neurology, Mayo Clinic, Rochester, 55905, MN, USA.
¹⁰⁶ Neuropsychiatric Institute, Prince of Wales Hospital, Sydney, 2031, Australia.
¹⁰⁷ Brain and Mind Centre-The University of Sydney, Camperdown, NSW, 2050, Australia.
¹⁰⁸ School of Medical Sciences, University of New South Wales, Sydney, 2052, Australia.
¹⁰⁹ Department of Clinical Chemistry, Fimlab Laboratories, Finnish Cardiovascular Research Center-Tampere, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, 33014, Finland.
¹¹⁰ Department of Clinical Chemistry, Finnish Cardiovascular Research Center-Tampere, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, 33014, Finland.
¹¹¹ Max Planck Institute for Human Development, Berlin, 14195, Germany.
¹¹² Technische Universität Dresden, Dresden, 01187, Germany.
¹¹³ Genetic and Molecular Epidemiology Group, Lübeck Interdisciplinary Platform for Genome Analytics, Institutes of Neurogenetics & Cardiogenetics, University of Lübeck, Lübeck, Germany.
¹¹⁴ Department of Neurology, School of Medicine, University of Washington, Seattle, 98195-6465, WA, USA.
¹¹⁵ Department of Epidemiology, University of Washington, Seattle, 98195, WA, USA.
¹¹⁶ Department of Neurology and Psychiatry, University of Pittsburgh, Pittsburgh, 15213, PA, USA.
¹¹⁷ Institute of Social Medicine, Occupational Health and Public Health (ISAP), University of Leipzig, Leipzig, 04103, Germany.
¹¹⁸ Department of Biological and Medical Psychology, University of Bergen, Bergen, 5009, Norway.
¹¹⁹ K. G. Jebsen Center for Neuropsychiatry, University of Bergen, Bergen, N-5009, Norway.
¹²⁰ Umeå Center for Functional Brain Imaging (UFBI), Umeå University, Umeå, SE-901 87, Sweden.
¹²¹ Department of Statistics, USBE Umeå University, S-907 97, Umeå, Sweden.
¹²² Institute for Molecular Bioscience, University of Queensland, Brisbane, 4072, Australia.
¹²³ The Institute of Medical Sciences, Aberdeen Biomedical Imaging Centre, University of Aberdeen, Aberdeen, AB25 2ZD, UK.
¹²⁴ Division of Brain Sciences, Department of Medicine, Imperial College, London, SW7 2AZ, UK.
¹²⁵ Department of Radiation Sciences, Umeå University, Umeå, SE-901 87, Sweden.
¹²⁶ Department of Integrative Medical Biology, Umeå University, Umeå, SE-901 87, Sweden.
¹²⁷ Centre for Integrated Genomic Medical Research, Institute of Population Health, University of Manchester, Manchester, M13 9PT, UK.
¹²⁸ Karolinska Institutet, Aging Research Center, Stockholm University, Stockholm, SE-113 30, Sweden.
¹²⁹ Department of Psychology, School of Philosophy, Psychology and Language Sciences, The University of Edinburgh, Edinburgh, EH8 9JZ, UK.
¹³⁰ Gen-Info LLC, Zagreb, 10000, Croatia.
¹³¹ Faculty of Medicine, University of Split, Split, 21000, Croatia.
¹³² Department of Psychology, Stanford University, Palo Alto, 94305-2130, CA, USA.
¹³³ Deparment of Health Services, University of Washington, Seattle, 98195-7660, WA, USA.
¹³⁴ Kaiser Permanente Washington Health Research Institute, Seattle, 98101, WA, USA.
¹³⁵ Department of Developmental Disability Neuropsychiatry, School of Psychiatry, University of New South Wales, Sydney, 2052, Australia.
¹³⁶ Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN, 47405-7007, USA.
¹³⁷ Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, 90502, USA.
¹³⁸ Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, 90509, CA, USA.
¹³⁹ Department of Genetics and Genomic Science and Institute for Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, 10029, NY, USA.
¹⁴⁰ Mental Illness Research, Education, and Clinical Center (VISN 2), James J. Peters VA Medical Center, Bronx, 10468, NY, USA.
¹⁴¹ Institute of Molecular Biology and Biochemistry, Centre for Molecular Medicine, Medical University of Graz, Graz, 8036, Austria.
¹⁴² Robert and Beverly Lewis Center for Neuroimaging, University of Oregon, Eugene, 97403, OR, USA.
¹⁴³ Department of Neurology, Boston University School of Medicine, Boston, 02118, MA, USA.
¹⁴⁴ The National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, 01702-5827, MA, USA.
¹⁴⁵ Department of Medical Biometry, Informatics and Epidemiology, University Hospital, Bonn, D-53012, Germany.
¹⁴⁶ Laboratory of NeuroGenetics, Department of Psychology & Neuroscience, Duke University, Durham, 27708-0086, NC, USA.
¹⁴⁷ Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, 2333, The Netherlands.
¹⁴⁸ Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, G12 8QQ, United Kingdom.
¹⁴⁹ Lieber Institute for Brain Development, Johns Hopkins University Medical Campus, Baltimore, 21205, MD, USA.
¹⁵⁰ Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, 45110, Greece.
¹⁵¹ Department of Public Health, University Hospital of Bordeaux, Bordeaux, 33076, France.
¹⁵² Department of Internal Medicine, Erasmus Medical Center, Rotterdam, 3015, The Netherlands.
¹⁵³ Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, University of Toronto, Toronto, M5T 1L8, Canada.
¹⁵⁴ Department of Public Health, University of Helsinki, Helsinki, 00014, Finland.
¹⁵⁵ Department of Radiology, Erasmus MC, Rotterdam, 3015, The Netherlands.
¹⁵⁶ Department of Psychiatry and Behavioral Sciences, Faculty of Medicine, University of Crete, Heraklion, GR-71003, Greece.
¹⁵⁷ Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, 77030, TX, USA.
¹⁵⁸ Human Genome Sequencing Center, Baylor College of Medicine, Houston, 77030-3411, TX, USA.
¹⁵⁹ Neuropsychiatric Genetics Research Group, Department of Psychiatry and Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, DO2 AY89, Ireland.
¹⁶⁰ Center for Translational and Systems Neuroimmunology, Department of Neurology, Columbia University Medical Center, New York, 10032, NY, USA.
¹⁶¹ Program in Medical and Population Genetics, Broad Institute, Cambridge, 02142, MA, USA.
¹⁶² Department of Neurology, University Hospital of Bordeaux, Bordeaux, 33000, France.
¹⁶³ Department of Global Health, University of Washington, Seattle, 98104, WA, USA.
¹⁶⁴ Department of Cardiology, Leiden University Medical Center, Leiden, 2333, The Netherlands.
¹⁶⁵ Institute for Behavioral Genetics, University of Colorado, Boulder, 80309, CO, USA.
¹⁶⁶ Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, CB10 1SA, UK.
¹⁶⁷ Department of Medical Genetics, University of Helsinki and University Central Hospital, Helsinki, 00014, Finland.
¹⁶⁸ Division of Neuroscience and Experimental Psychology, School of Biological Sciences, Manchester Academic Health Science Centre, and Manchester Medical School, Institute of Brain, Behaviour, and Mental Health, University of Manchester, Manchester, M13 9PL, UK.
¹⁶⁹ Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, 20520, Finland.
¹⁷⁰ School of Medicine and Public Health, University of Newcastle, New South Wales, 2308, Australia.
¹⁷¹ Neuroscience Research Australia, Sydney, 2031, Australia.
¹⁷² Faculty of Medicine, University of New South Wales, Sydney, 2052, Australia.
¹⁷³ Alzheimer Scotland Dementia Research Centre, University of Edinburgh, Edinburgh, EH8 9JZ, UK.
¹⁷⁴ Division of Nephrology and Hypertension, Department of Internal Medicine, Mayo Clinic, Rochester, MN, 55905, USA.
¹⁷⁵ Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, 04103, Germany.
¹⁷⁶ Day Clinic for Cognitive Neurology, University Hospital Leipzig, Leipzig, 04103, Germany.
¹⁷⁷ Division of Psychiatry Research, Zucker Hillside Hospital, Glen Oaks, 11004, NY, USA.
¹⁷⁸ Department of Psychiatry, Hofstra Northwell School of Medicine, Hempstead, 11549, NY, USA.
¹⁷⁹ Division of Psychiatry, University of Edinburgh, Edinburgh, EH10 5HF, UK.
¹⁸⁰ MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, SO16 6YD, UK.
¹⁸¹ Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, University of Texas Health Sciences Center, San Antonio, 78229, TX, USA.
¹⁸² Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, School of Philosophy, Psychology and Language Sciences, The University of Edinburgh, Edinburgh, EH8 9JZ, UK. i.deary@ed.ac.uk.

PMID: 29844566
PMCID: PMC5974083
DOI: 10.1038/s41467-018-04362-x

Meta-Analysis

Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function

Gail Davies et al. Nat Commun. 2018.

. 2018 May 29;9(1):2098.

doi: 10.1038/s41467-018-04362-x.

Authors

Affiliations

¹ Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, School of Philosophy, Psychology and Language Sciences, The University of Edinburgh, Edinburgh, EH8 9JZ, UK.
² Institute of Mental Health, Singapore, 539747, Singapore.
³ Medical Genetics Section, Centre for Genomic & Experimental Medicine, MRC Institute of Genetics & Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, EH4 2XU, UK.
⁴ BrainWorkup, LLC, Los Angeles, 90033, CA, USA.
⁵ Department of Psychiatry and Behavioral Sciences, Keck School of Medicine, University of Southern California, Los Angeles, 90033, CA, USA.
⁶ Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, De Crespigny Park, Denmark Hill, London, SE5 8AF, UK.
⁷ Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, 20520, Finland.
⁸ Department of Internal Medicine, Satakunta Central Hospital, Pori, 28100, Finland.
⁹ Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Teviot Place, Edinburgh, EH8 9AG, Scotland.
¹⁰ Max Planck Institute for Molecular Genetics, Berlin, 14195, Germany.
¹¹ Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, 98101, Washington, USA.
¹² Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, 10029, NY, USA.
¹³ Mental Illness Research, Education, and Clinical Center (VISN 3), James J. Peters VA Medical Center, Bronx, 10468, NY, USA.
¹⁴ Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, 02115, MA, USA.
¹⁵ NORMENT, K.G. Jebsen Centre for Psychosis Research, Department of Clinical Science, University of Bergen, Bergen, 5021, Norway.
¹⁶ Dr. Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, 5020, Norway.
¹⁷ Center for Psychiatric Neuroscience, Feinstein Institute for Medical Research, Manhasset, 11030, NY, USA.
¹⁸ Department of Medical Genetics, Oslo University Hospital, University of Bergen, Oslo, 0424, Norway.
¹⁹ Department of Psychology, University of Oslo, Oslo, 0373, Norway.
²⁰ Division of Mental Health and Addiction, Oslo University Hospital, Oslo, 0315, Norway.
²¹ Department of Psychology, University of Crete, Crete, GR-74100, Greece.
²² Department of Psychiatry, University of California, San Diego, 92093, CA, USA.
²³ Center for Behavior Genetics of Aging, University of California, San Diego, 92093, CA, USA.
²⁴ Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, EH4 2XU, UK.
²⁵ Generation Scotland, Centre for Genomic and Experimental Medicine, University of Edinburgh, Edinburgh, EH4 2XU, UK.
²⁶ Department of Neurology, Clinical Division of Neurogeriatrics, Medical University of Graz, Graz, 8036, Austria.
²⁷ Institute of Medical Informatics Statistics and Documentation, Medical University of Graz, Graz, 8036, Austria.
²⁸ Department of Epidemiology, Erasmus University Medical Center, Rotterdam, 3015, The Netherlands.
²⁹ Department of Radiology and Nuclear Medicine, Erasmus University Medical Center, Rotterdam, 3015, The Netherlands.
³⁰ Department of Neurology, Erasmus University Medical Center, Rotterdam, xxxxxx, The Netherlands.
³¹ Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, SE-171 77, Sweden.
³² Department of Psychiatry, Yale University School of Medicine, New Haven, 06511, CT, USA.
³³ Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, 00014, Finland.
³⁴ Helsinki Collegium for Advanced Studies, University of Helsinki, Helsinki, 00014, Finland.
³⁵ Department of Psychiatry and Psychotherapy, University of Cologne, Cologne, D-50937, Germany.
³⁶ Department of Biostatistics, Boston University School of Public Health, Boston, 02118, MA, USA.
³⁷ Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, 2031, Australia.
³⁸ Neuroimaging, Cognition & Genomics (NICOG) Centre, School of Psychology and Discipline of Biochemistry, National University of Ireland Galway, Galway, H91 TK33, Ireland.
³⁹ Medical Research Institute and Faculty of Health, University of Newcastle, New South Wa0les, 2308, Australia.
⁴⁰ Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, FI-00014, Finland.
⁴¹ Centre for EpidemiologyDivision of Population Health, Health Services Research & Primary Care, The University of Manchester, Manchester, M13 9PL, UK.
⁴² Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, W2 1PG, UK.
⁴³ Department of Psychology, University of California Riverside, Riverside, 92521, CA, USA.
⁴⁴ University of Bordeaux, Bordeaux Population Health Research Center, INSERM UMR 1219, F-33000, Bordeaux, France.
⁴⁵ Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, 04107, Germany.
⁴⁶ LIFE-Leipzig Research Center for Civilization Diseases, University of Leipzig, Leipzig, 04107, Germany.
⁴⁷ Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, 48109, USA.
⁴⁸ Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI, 48104, USA.
⁴⁹ Icelandic Heart Association, Kopavogur, IS-201, Iceland.
⁵⁰ University of Iceland, Reykjavik, 101, Iceland.
⁵¹ Department of Respiratory Medicine, Ghent University Hospital, De Pintelaan 185, 9000, Ghent, Belgium.
⁵² Section of Gerontology and Geriatrics, Department of Internal Medicine, Leiden University Medical Center, Leiden, 2333, The Netherlands.
⁵³ Department of Medicine, Division of Geriatrics, University of Mississippi Medical Center, Jackson, 39216, MS, USA.
⁵⁴ Queensland Brain Institute, University of Queensland, Brisbane, 4072, Australia.
⁵⁵ Centre for Advanced Imaging, University of Queensland, Brisbane, 4072, Australia.
⁵⁶ Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, 60612, IL, USA.
⁵⁷ Department of Neurological Sciences, Rush University Medical Center, Chicago, 60612, IL, USA.
⁵⁸ National Ageing Research Institute, Royal Melbourne Hospital, Victoria, 3052, Australia.
⁵⁹ Academic Unit for Psychiatry of Old Age, University of Melbourne, St George's Hospital, Kew, 3010, Australia.
⁶⁰ Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1167-LabEx DISTALZ, F-59000, Lille, France.
⁶¹ Norwegian Centre for Mental Disorders Research (NORMENT), Institute of Clinical Medicine, University of Oslo, Oslo, 0372, Norway.
⁶² Mathematics and Statistics, Murdoch University, Perth, 6150, Australia.
⁶³ Hunter Medical Research Institute and Faculty of Health, University of Newcastle, New South Wales, 2305, Australia.
⁶⁴ Department of NeurologyBryan Alzheimer's Disease Research Center, and Center for Genomic and Computational Biology, Duke University Medical Center, Durham, 27708, NC, USA.
⁶⁵ Psychiatry and Behavioral Sciences, Division of Medical Psychology, and Department of Neurology, Duke University Medical Center, Durham, 27708, NC, USA.
⁶⁶ Department of Psychiatry, Johns Hopkins University School of Medicine, MD, Baltimore, 21287, USA.
⁶⁷ McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, MD, Baltimore, 21287, USA.
⁶⁸ Institute of Human Genetics, University of Bonn, Bonn, 53113, Germany.
⁶⁹ Department of Genomics, Life and Brain Center, University of Bonn, Bonn, 53113, Germany.
⁷⁰ Departments of Behavioral Sciences, Rush University Medical Center, Chicago, 60612, IL, USA.
⁷¹ Dementia Centre for Research Collaboration, University of New South Wales, Sydney, 2031, NSW, Australia.
⁷² Department of Psychology, Yale University, New Haven, 06520, CT, USA.
⁷³ Human Longevity Inc, Durham, 27709, NC, USA.
⁷⁴ UCLA Semel Institute for Neuroscience and Human Behavior, Los Angeles, 90024, CA, USA.
⁷⁵ 23andMe, Inc., Mountain View, 94041, CA, USA.
⁷⁶ Department of Cognitive Science, University of California, San Diego, La Jolla, 92093, CA, USA.
⁷⁷ Department of Neurosciences, University of California, San Diego, La Jolla, 92093, CA, USA.
⁷⁸ Department of Radiology, University of California, San Diego, La Jolla, 92093, CA, USA.
⁷⁹ MRC-PHE Centre for Environment, School of Public Health, Imperial College London, London, W2 1PG, UK.
⁸⁰ Department of Psychology, Virginia Commonwealth University, Richmond, 23284, VA, USA.
⁸¹ Clinical and Translational Neuroscience Branch, Intramural Research Program, National Institute of Mental Health, National Institute of Health, Bethesda, 20892, MD, USA.
⁸² National Institute for Health and Welfare, Helsinki, FI-00271, Finland.
⁸³ Department of General Practice and Primary Health Care, University of Helsinki, Helsinki, 00290, Finland.
⁸⁴ Helsinki University Central Hospital, Unit of General Practice, Helsinki, FI-00029, Finland.
⁸⁵ Folkhälsan Research Centre, Helsinki, 2018, Finland.
⁸⁶ Robertson Centre for Biostatistics, University of Glasgow, Glasgow, G12 8QQ, United Kingdom.
⁸⁷ Department of Psychiatry, Martin Luther University of Halle-Wittenberg, Halle, 06108, Germany.
⁸⁸ Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, 23298, VA, USA.
⁸⁹ QIMR Berghofer Medical Research Institute, Brisbane, 4029, Australia.
⁹⁰ Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, 21287, MD, USA.
⁹¹ Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, 21205, MD, USA.
⁹² Department of Data Science, University of Mississippi Medical Center, Jackson, 39216, MS, USA.
⁹³ Intramural Research Program National Institutes on Aging, National Institutes of Health, Bethesda, 20892, MD, USA.
⁹⁴ Department of Psychiatry, National and Kapodistrian University of Athens Medical School, Eginition Hospital, Athens, 11528, Greece.
⁹⁵ University Mental Health Research Institute, Athens, GR-156 01, Greece.
⁹⁶ Neurobiology Research Institute, Theodor-Theohari Cozzika Foundation, Athens, 11521, Greece.
⁹⁷ Department of Epidemiology, University of North Carolina Gillings School of Global Public Health, Chapel Hill, 27599, NC, USA.
⁹⁸ Department of Clinical Physiology, Tampere University Hospital, and Finnish Cardiovascular Research Center, Tampere, FI-33014, Finland.
⁹⁹ Faculty of Medicine and Life Sciences, University of Tampere, Tampere, 33521, Finland.
¹⁰⁰ Department of Clinical Physiology, Finnish Cardiovascular Research Center-Tampere, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, 33014, Finland.
¹⁰¹ Department of Psychiatry Medical Faculty, University of Cologne, Cologne, 50923, Germany.
¹⁰² Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, 53127, Germany.
¹⁰³ German Center for Neurodegenerative Diseases (DZNE), Bonn, 53127, Germany.
¹⁰⁴ Department for Neurodegenerative Diseases and Geriatric Psychiatry, University of Bonn, Bonn, 53127, Germany.
¹⁰⁵ Department of Neurology, Mayo Clinic, Rochester, 55905, MN, USA.
¹⁰⁶ Neuropsychiatric Institute, Prince of Wales Hospital, Sydney, 2031, Australia.
¹⁰⁷ Brain and Mind Centre-The University of Sydney, Camperdown, NSW, 2050, Australia.
¹⁰⁸ School of Medical Sciences, University of New South Wales, Sydney, 2052, Australia.
¹⁰⁹ Department of Clinical Chemistry, Fimlab Laboratories, Finnish Cardiovascular Research Center-Tampere, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, 33014, Finland.
¹¹⁰ Department of Clinical Chemistry, Finnish Cardiovascular Research Center-Tampere, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, 33014, Finland.
¹¹¹ Max Planck Institute for Human Development, Berlin, 14195, Germany.
¹¹² Technische Universität Dresden, Dresden, 01187, Germany.
¹¹³ Genetic and Molecular Epidemiology Group, Lübeck Interdisciplinary Platform for Genome Analytics, Institutes of Neurogenetics & Cardiogenetics, University of Lübeck, Lübeck, Germany.
¹¹⁴ Department of Neurology, School of Medicine, University of Washington, Seattle, 98195-6465, WA, USA.
¹¹⁵ Department of Epidemiology, University of Washington, Seattle, 98195, WA, USA.
¹¹⁶ Department of Neurology and Psychiatry, University of Pittsburgh, Pittsburgh, 15213, PA, USA.
¹¹⁷ Institute of Social Medicine, Occupational Health and Public Health (ISAP), University of Leipzig, Leipzig, 04103, Germany.
¹¹⁸ Department of Biological and Medical Psychology, University of Bergen, Bergen, 5009, Norway.
¹¹⁹ K. G. Jebsen Center for Neuropsychiatry, University of Bergen, Bergen, N-5009, Norway.
¹²⁰ Umeå Center for Functional Brain Imaging (UFBI), Umeå University, Umeå, SE-901 87, Sweden.
¹²¹ Department of Statistics, USBE Umeå University, S-907 97, Umeå, Sweden.
¹²² Institute for Molecular Bioscience, University of Queensland, Brisbane, 4072, Australia.
¹²³ The Institute of Medical Sciences, Aberdeen Biomedical Imaging Centre, University of Aberdeen, Aberdeen, AB25 2ZD, UK.
¹²⁴ Division of Brain Sciences, Department of Medicine, Imperial College, London, SW7 2AZ, UK.
¹²⁵ Department of Radiation Sciences, Umeå University, Umeå, SE-901 87, Sweden.
¹²⁶ Department of Integrative Medical Biology, Umeå University, Umeå, SE-901 87, Sweden.
¹²⁷ Centre for Integrated Genomic Medical Research, Institute of Population Health, University of Manchester, Manchester, M13 9PT, UK.
¹²⁸ Karolinska Institutet, Aging Research Center, Stockholm University, Stockholm, SE-113 30, Sweden.
¹²⁹ Department of Psychology, School of Philosophy, Psychology and Language Sciences, The University of Edinburgh, Edinburgh, EH8 9JZ, UK.
¹³⁰ Gen-Info LLC, Zagreb, 10000, Croatia.
¹³¹ Faculty of Medicine, University of Split, Split, 21000, Croatia.
¹³² Department of Psychology, Stanford University, Palo Alto, 94305-2130, CA, USA.
¹³³ Deparment of Health Services, University of Washington, Seattle, 98195-7660, WA, USA.
¹³⁴ Kaiser Permanente Washington Health Research Institute, Seattle, 98101, WA, USA.
¹³⁵ Department of Developmental Disability Neuropsychiatry, School of Psychiatry, University of New South Wales, Sydney, 2052, Australia.
¹³⁶ Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN, 47405-7007, USA.
¹³⁷ Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, 90502, USA.
¹³⁸ Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, 90509, CA, USA.
¹³⁹ Department of Genetics and Genomic Science and Institute for Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, 10029, NY, USA.
¹⁴⁰ Mental Illness Research, Education, and Clinical Center (VISN 2), James J. Peters VA Medical Center, Bronx, 10468, NY, USA.
¹⁴¹ Institute of Molecular Biology and Biochemistry, Centre for Molecular Medicine, Medical University of Graz, Graz, 8036, Austria.
¹⁴² Robert and Beverly Lewis Center for Neuroimaging, University of Oregon, Eugene, 97403, OR, USA.
¹⁴³ Department of Neurology, Boston University School of Medicine, Boston, 02118, MA, USA.
¹⁴⁴ The National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, 01702-5827, MA, USA.
¹⁴⁵ Department of Medical Biometry, Informatics and Epidemiology, University Hospital, Bonn, D-53012, Germany.
¹⁴⁶ Laboratory of NeuroGenetics, Department of Psychology & Neuroscience, Duke University, Durham, 27708-0086, NC, USA.
¹⁴⁷ Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, 2333, The Netherlands.
¹⁴⁸ Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, G12 8QQ, United Kingdom.
¹⁴⁹ Lieber Institute for Brain Development, Johns Hopkins University Medical Campus, Baltimore, 21205, MD, USA.
¹⁵⁰ Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, 45110, Greece.
¹⁵¹ Department of Public Health, University Hospital of Bordeaux, Bordeaux, 33076, France.
¹⁵² Department of Internal Medicine, Erasmus Medical Center, Rotterdam, 3015, The Netherlands.
¹⁵³ Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, University of Toronto, Toronto, M5T 1L8, Canada.
¹⁵⁴ Department of Public Health, University of Helsinki, Helsinki, 00014, Finland.
¹⁵⁵ Department of Radiology, Erasmus MC, Rotterdam, 3015, The Netherlands.
¹⁵⁶ Department of Psychiatry and Behavioral Sciences, Faculty of Medicine, University of Crete, Heraklion, GR-71003, Greece.
¹⁵⁷ Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, 77030, TX, USA.
¹⁵⁸ Human Genome Sequencing Center, Baylor College of Medicine, Houston, 77030-3411, TX, USA.
¹⁵⁹ Neuropsychiatric Genetics Research Group, Department of Psychiatry and Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, DO2 AY89, Ireland.
¹⁶⁰ Center for Translational and Systems Neuroimmunology, Department of Neurology, Columbia University Medical Center, New York, 10032, NY, USA.
¹⁶¹ Program in Medical and Population Genetics, Broad Institute, Cambridge, 02142, MA, USA.
¹⁶² Department of Neurology, University Hospital of Bordeaux, Bordeaux, 33000, France.
¹⁶³ Department of Global Health, University of Washington, Seattle, 98104, WA, USA.
¹⁶⁴ Department of Cardiology, Leiden University Medical Center, Leiden, 2333, The Netherlands.
¹⁶⁵ Institute for Behavioral Genetics, University of Colorado, Boulder, 80309, CO, USA.
¹⁶⁶ Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, CB10 1SA, UK.
¹⁶⁷ Department of Medical Genetics, University of Helsinki and University Central Hospital, Helsinki, 00014, Finland.
¹⁶⁸ Division of Neuroscience and Experimental Psychology, School of Biological Sciences, Manchester Academic Health Science Centre, and Manchester Medical School, Institute of Brain, Behaviour, and Mental Health, University of Manchester, Manchester, M13 9PL, UK.
¹⁶⁹ Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, 20520, Finland.
¹⁷⁰ School of Medicine and Public Health, University of Newcastle, New South Wales, 2308, Australia.
¹⁷¹ Neuroscience Research Australia, Sydney, 2031, Australia.
¹⁷² Faculty of Medicine, University of New South Wales, Sydney, 2052, Australia.
¹⁷³ Alzheimer Scotland Dementia Research Centre, University of Edinburgh, Edinburgh, EH8 9JZ, UK.
¹⁷⁴ Division of Nephrology and Hypertension, Department of Internal Medicine, Mayo Clinic, Rochester, MN, 55905, USA.
¹⁷⁵ Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, 04103, Germany.
¹⁷⁶ Day Clinic for Cognitive Neurology, University Hospital Leipzig, Leipzig, 04103, Germany.
¹⁷⁷ Division of Psychiatry Research, Zucker Hillside Hospital, Glen Oaks, 11004, NY, USA.
¹⁷⁸ Department of Psychiatry, Hofstra Northwell School of Medicine, Hempstead, 11549, NY, USA.
¹⁷⁹ Division of Psychiatry, University of Edinburgh, Edinburgh, EH10 5HF, UK.
¹⁸⁰ MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, SO16 6YD, UK.
¹⁸¹ Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, University of Texas Health Sciences Center, San Antonio, 78229, TX, USA.
¹⁸² Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, School of Philosophy, Psychology and Language Sciences, The University of Edinburgh, Edinburgh, EH8 9JZ, UK. i.deary@ed.ac.uk.

PMID: 29844566
PMCID: PMC5974083
DOI: 10.1038/s41467-018-04362-x

Erratum in

Author Correction: Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function.
Davies G, Lam M, Harris SE, Trampush JW, Luciano M, Hill WD, Hagenaars SP, Ritchie SJ, Marioni RE, Fawns-Ritchie C, Liewald DCM, Okely JA, Ahola-Olli AV, Barnes CLK, Bertram L, Bis JC, Burdick KE, Christoforou A, DeRosse P, Djurovic S, Espeseth T, Giakoumaki S, Giddaluru S, Gustavson DE, Hayward C, Hofer E, Ikram MA, Karlsson R, Knowles E, Lahti J, Leber M, Li S, Mather KA, Melle I, Morris D, Oldmeadow C, Palviainen T, Payton A, Pazoki R, Petrovic K, Reynolds CA, Sargurupremraj M, Scholz M, Smith JA, Smith AV, Terzikhan N, Thalamuthu A, Trompet S, van der Lee SJ, Ware EB, Windham BG, Wright MJ, Yang J, Yu J, Ames D, Amin N, Amouyel P, Andreassen OA, Armstrong NJ, Assareh AA, Attia JR, Attix D, Avramopoulos D, Bennett DA, Böhmer AC, Boyle PA, Brodaty H, Campbell H, Cannon TD, Cirulli ET, Congdon E, Conley ED, Corley J, Cox SR, Dale AM, Dehghan A, Dick D, Dickinson D, Eriksson JG, Evangelou E, Faul JD, Ford I, Freimer NA, Gao H, Giegling I, Gillespie NA, Gordon SD, Gottesman RF, Griswold ME, Gudnason V, Harris TB, Hartmann AM, Hatzimanolis A, Heiss G, Holliday EG, Joshi PK, Kähönen M, Kardia SLR, Karlsson I, Kleineidam L, Knopman DS, Kochan NA, Konte B, Kwok JB, Le Hellard S, Lee T,… See abstract for full author list ➔ Davies G, et al. Nat Commun. 2019 May 1;10(1):2068. doi: 10.1038/s41467-019-10160-w. Nat Commun. 2019. PMID: 31043617 Free PMC article.

Abstract

General cognitive function is a prominent and relatively stable human trait that is associated with many important life outcomes. We combine cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N = 300,486; age 16-102) and find 148 genome-wide significant independent loci (P < 5 × 10^-8) associated with general cognitive function. Within the novel genetic loci are variants associated with neurodegenerative and neurodevelopmental disorders, physical and psychiatric illnesses, and brain structure. Gene-based analyses find 709 genes associated with general cognitive function. Expression levels across the cortex are associated with general cognitive function. Using polygenic scores, up to 4.3% of variance in general cognitive function is predicted in independent samples. We detect significant genetic overlap between general cognitive function, reaction time, and many health variables including eyesight, hypertension, and longevity. In conclusion we identify novel genetic loci and pathways contributing to the heritability of general cognitive function.

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Conflict of interest statement

A.M.D. is a Founder of and holds equity in CorTechs Labs, Inc., and serves on its Scientific Advisory Board. He is a member of the Scientific Advisory Board of Human Longevity, Inc., and receives funding through research agreements with General Electric Healthcare and Medtronic, Inc. The terms of these arrangements have been reviewed and approved by UCSD in accordance with its conflict of interest policies. B.M.P. serves on a DSMB for a clinical trial of a device funded by the manufacturer (Zoll LifeCor), and on the steering committee of the Yale Open Data Access Project funded by Johnson & Johnson. I.J.D. is a participant in UK Biobank. All other authors declare no competing interests.

Figures

**Fig. 1**
The hierarchical model of cognitive function variance. At level 1, individuals differ in specific tests that assess the various cognitive domains. Scores on all the tests correlate positively. It is found that there are especially strong correlations among the tests of the same domain, so a latent trait at the domain level can be extracted to represent this common variance. It is then found that individuals who do well in one domain also tend to do well in the other domains, so a general cognitive latent trait called g can be extracted. This model allows researchers to partition cognitive performance variance into these different levels. They can then explore the causes and consequences of variance at different levels of cognitive specificity-generality. For example, there are genetic and ageing effects on g and on some specific domains, such as memory and speed of processing. Note that the specific-test-level variance contains variation in the performance of skills that are specific to the individual test and also contains error variance. (Reproduced, with permission, from ref. )

**Fig. 2**
Association results for general cognitive function. SNP-based (a) and gene-based (b) association results in 300,486 individuals. The red line indicates the threshold for genome-wide significance: P < 5 × 10⁻⁸ for (a), P < 2.75 × 10⁻⁶ for (b); the blue line in (a) indicates the threshold for suggestive significance: P < 1 × 10⁻⁵

**Fig. 3**
Functional analyses of general cognitive function. Analyses include general cognitive function-associated SNPs, independent significant SNPs, and all SNPs in LD with independent significant SNPs. Functional consequences of SNPs on genes (a) indicated by functional annotation assigned by ANNOVAR. MAGMA gene-property analysis results; results are shown for average expression of 30 general tissue types (b) and 53 specific tissue types (c). The dotted line indicates the Bonferroni-corrected α level

**Fig. 4**
Association results for reaction time. SNP-based (a) and gene-based (b) association results in 330,069 individuals. The red line indicates the threshold for genome-wide significance: P < 5 × 10⁻⁸ for (a), P < 2.75 × 10⁻⁶ for (b); the blue line in (a) indicates the threshold for suggestive significance: P < 1 × 10⁻⁵

**Fig. 5**
Functional analyses of reaction time. Analyses include reaction time-associated SNPs, independent significant SNPs, and all SNPs in LD with independent significant SNPs. Functional consequences of SNPs on genes (a) indicated by functional annotation assigned by ANNOVAR. MAGMA gene-property analysis results; results are shown for average expression of 30 general tissue types (b) and 53 specific tissue types (c). The dotted line indicates the Bonferroni-corrected α level

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References

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Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function

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Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function

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