. 2022 Nov;27(11):4419-4431.

doi: 10.1038/s41380-022-01710-8. Epub 2022 Aug 16.

Genome-wide meta-analyses reveal novel loci for verbal short-term memory and learning

Jari Lahti^{1

2}, Samuli Tuominen³, Qiong Yang⁴, Giulio Pergola^{5

6}, Shahzad Ahmad⁷, Najaf Amin⁷, Nicola J Armstrong⁸, Alexa Beiser^{4

9}, Katharina Bey^{10

11}, Joshua C Bis¹², Eric Boerwinkle^{13

14}, Jan Bressler¹³, Archie Campbell^{15

16}, Harry Campbell¹⁷, Qiang Chen⁵, Janie Corley¹⁸, Simon R Cox¹⁸, Gail Davies¹⁸, Philip L De Jager¹⁹, Eske M Derks²⁰, Jessica D Faul²¹, Annette L Fitzpatrick^{22

23

24}, Alison E Fohner^{23

25}, Ian Ford²⁶, Myriam Fornage²⁷, Zachary Gerring²⁰, Hans J Grabe^{28

29}, Francine Grodstein^{30

31}, Vilmundur Gudnason^{32

33}, Eleanor Simonsick³⁴, Elizabeth G Holliday³⁵, Peter K Joshi^{17

36}, Eero Kajantie^{37

38

39}, Jaakko Kaprio^{40

41}, Pauliina Karell⁴⁰, Luca Kleineidam^{11

42}, Maria J Knol⁷, Nicole A Kochan^{43

44}, John B Kwok^{45

46}, Markus Leber⁴⁷, Max Lam^{48

49}, Teresa Lee^{43

44}, Shuo Li⁴, Anu Loukola⁵⁰, Tobias Luck^{51

52

53}, Riccardo E Marioni^{15

54}, Karen A Mather^{43

55}, Sarah Medland⁵⁶, Saira S Mirza^{7

57}, Mike A Nalls^{58

59}, Kwangsik Nho^{60

61

62}, Adrienne O'Donnell^{4

9}, Christopher Oldmeadow⁶³, Jodie Painter⁵⁶, Alison Pattie¹⁸, Simone Reppermund^{43

64}, Shannon L Risacher^{60

62}, Richard J Rose⁶⁵, Vijay Sadashivaiah⁵, Markus Scholz^{66

67}, Claudia L Satizabal^{9

68

69}, Peter W Schofield⁷⁰, Katharina E Schraut^{17

71}, Rodney J Scott^{72

73}, Jeannette Simino⁷⁴, Albert V Smith^{32

33}, Jennifer A Smith^{75

76}, David J Stott⁷⁷, Ida Surakka⁷⁸, Alexander Teumer⁷⁹, Anbupalam Thalamuthu⁴³, Stella Trompet⁸⁰, Stephen T Turner⁸¹, Sven J van der Lee^{7

82}, Arno Villringer^{83

84}, Uwe Völker⁸⁵, Robert S Wilson⁸⁶, Katharina Wittfeld^{28

29}, Eero Vuoksimaa⁴⁰, Rui Xia⁸⁷, Kristine Yaffe⁸⁸, Lei Yu⁸⁶, Habil Zare^{89

90

91}, Wei Zhao⁷⁵, David Ames^{92

93}, John Attia^{35

63}, David A Bennett⁸⁶, Henry Brodaty^{43

94}, Daniel I Chasman^{95

96}, Aaron L Goldman⁵, Caroline Hayward⁹⁷, M Arfan Ikram⁷, J Wouter Jukema⁹⁸, Sharon L R Kardia⁷⁵, Todd Lencz⁹⁹, Markus Loeffler^{66

67}, Venkata S Mattay^{5

100}, Aarno Palotie^{40

101

102}, Bruce M Psaty^{12

103

104}, Alfredo Ramirez^{42

47}, Paul M Ridker^{95

96}, Steffi G Riedel-Heller¹⁰⁵, Perminder S Sachdev^{43

44}, Andrew J Saykin^{60

61

62}, Martin Scherer¹⁰⁶, Peter R Schofield^{46

107}, Stephen Sidney¹⁰⁸, John M Starr^{18

109}, Julian Trollor^{43

110}, William Ulrich⁵, Michael Wagner^{11

42}, David R Weir²¹, James F Wilson^{17

97}, Margaret J Wright^{111

112}, Daniel R Weinberger^{5

113

114

115}, Stephanie Debette^{116

117}, Johan G Eriksson^{118

119

120}, Thomas H Mosley Jr¹²¹, Lenore J Launer¹²², Cornelia M van Duijn^{7

123}, Ian J Deary^{18

54}, Sudha Seshadri^{9

68

69}, Katri Räikkönen³

Affiliations

¹ Department of Psychology and Logopedics, University of Helsinki, Helsinki, Finland. jari.lahti@helsinki.fi.
² Turku Institute of Advanced Studies, University of Turku, Turku, Finland. jari.lahti@helsinki.fi.
³ Department of Psychology and Logopedics, University of Helsinki, Helsinki, Finland.
⁴ Department of Biostatistics, Boston University, Boston, MA, USA.
⁵ Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA.
⁶ Department of Basic Medical Science, Neuroscience, and Sense Organs, University of Bari Aldo Moro, Bari, Italy.
⁷ Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
⁸ Department of Mathematics and Statistics, Murdoch University, Murdoch, WA, Australia.
⁹ Framingham Heart Study, Framingham, MA, USA.
¹⁰ Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany.
¹¹ German Center for Neurodegenerative Diseases, Bonn, Germany.
¹² Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.
¹³ Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX, USA.
¹⁴ Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.
¹⁵ Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
¹⁶ Usher Institute, University of Edinburgh, Edinburgh, UK.
¹⁷ Centre for Global Health Research, Usher Institute, University of Edinburgh, Edinburgh, UK.
¹⁸ Department of Psychology, Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.
¹⁹ Center for Translational and Computational Neuroimmunology, Columbia University Medical Center, New York, NY, USA.
²⁰ Translational Neurogenomics Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
²¹ Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI, USA.
²² Department of Family Medicine, University of Washington, Seattle, WA, USA.
²³ Department of Epidemiology, University of Washington, Seattle, WA, USA.
²⁴ Department of Global Health, University of Washington, Seattle, WA, USA.
²⁵ Institute of Public Health Genetics, University of Washington, Seattle, WA, USA.
²⁶ Robertson Center for Biostatistics, University of Glasgow, Glasgow, UK.
²⁷ McGovern Medical School, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA.
²⁸ Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
²⁹ German Center for Neurodegenerative Diseases, Greifswald, Germany.
³⁰ Channing Laboratory, Brigham and Women's Hospital, Boston, MA, USA.
³¹ Harvard School of Public Health, Boston, MA, USA.
³² Icelandic Heart Assocation, Kopavogur, Iceland.
³³ Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
³⁴ Translational Gerontology Branch, National Institute on Aging, Intramural Research Program, National Institutes of Health, Baltimore, MD, USA.
³⁵ School of Medicine and Public Health, University of Newcastle, Callaghan, NSW, Australia.
³⁶ Institute of Social and Preventive Medicine, University of Lausanne, Lausanne, Switzerland.
³⁷ National Institute for Health and Welfare, Helsinki and Oulu, Oulu, Finland.
³⁸ Hospital for Children and Adolescents, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
³⁹ PEDEGO Research Unit, MRC Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland.
⁴⁰ Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
⁴¹ Department of Public Health, University of Helsinki, Helsinki, Finland.
⁴² Department for Neurodegenerative Diseases and Geriatric Psychiatry, University of Bonn, Bonn, Germany.
⁴³ Centre for Healthy Brain Ageing (CHeBA), School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia.
⁴⁴ Neuropsychiatric Institute, Prince of Wales Hospital, Sydney, NSW, Australia.
⁴⁵ Brain and Mind Centre, The University of Sydney, Sydney, NSW, Australia.
⁴⁶ School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia.
⁴⁷ Department of Psychiatry, University of Cologne, Cologne, Germany.
⁴⁸ Psychiatry Research, Zucker Hillside Hospital, Glen Oaks, NY, USA.
⁴⁹ Stanley Center for Psychiatric Research, Broad Institute, Cambridge, MA, USA.
⁵⁰ Helsinki Biobank, University of Helsinki Central Hospital, Helsinki, Finland.
⁵¹ Department of Economic and Social Sciences & Institute of Social Medicine, Rehabilitation Sciences and Healthcare Research, University of Applied Sciences Nordhausen, Nordhausen, Germany.
⁵² University of Leipzig, Leipzig, Germany.
⁵³ LIFE Leipzig Research Center for Civilization Diseases, Leipzig, Germany.
⁵⁴ Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.
⁵⁵ Sunnybrook Health Sciences Centre, University of Toronto, Randwick, NSW, Australia.
⁵⁶ QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
⁵⁷ Department of Neurology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada.
⁵⁸ Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD, USA.
⁵⁹ Data Tecnica International, Glen Echo, MD, USA.
⁶⁰ Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, USA.
⁶¹ Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN, USA.
⁶² Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indianapolis, IN, USA.
⁶³ Clinical Research Design, IT and Statistical Support Unit, Hunter Medical Research Institute, New Lambton, NSW, Australia.
⁶⁴ Department of Developmental Disability Neuropsychiatry, School of Psychiatry, University of New South Wales, Sydney, NSW, Australia.
⁶⁵ Department of Psychological & Brain Sciences, Indiana University Bloomington, Bloomington, IN, USA.
⁶⁶ Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.
⁶⁷ LIFE Research Center for Civilization Diseases, University of Leipzig, Leipzig, Germany.
⁶⁸ Department of Neurology, Boston University, Boston, MA, USA.
⁶⁹ Glenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases, University of Texas Health Sciences Center, San Antonio, TX, USA.
⁷⁰ Neuropsychiatry Service, Hunter New England Local Health District, Charlestown, NSW, Australia.
⁷¹ Centre for Cardiovascular Sciences, Queen's Medical Research Institute, Royal Infirmary of Edinburgh, University of Edinburgh, Edinburgh, UK.
⁷² School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, NSW, Australia.
⁷³ Hunter Medical Research Institute, New Lambton, NSW, Australia.
⁷⁴ Department of Data Science, University of Mississippi Medical Center, Jackson, MS, USA.
⁷⁵ Department of Epidemiology, University of Michigan, Ann Arbor, MI, USA.
⁷⁶ Institute of Social Research, Survey Research Center, University of Michigan, Ann Arbor, MI, USA.
⁷⁷ Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
⁷⁸ Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
⁷⁹ Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
⁸⁰ Section of Gerontology and Geriatrics, Department of Internal Medicine, Leiden University Medical Center, Leiden, The Netherlands.
⁸¹ Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA.
⁸² Department of Neurology and Alzheimer Center, VU University Medical Center, Amsterdam, The Netherlands.
⁸³ Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany.
⁸⁴ Day Clinic for Cognitive Neurology, University Hospital Leipzig, Leipzig, Germany.
⁸⁵ Interfaculty Institute for Genetics and Functional Genomics, Department Functional Genomics, University Medicine Greifswald, Greifswald, Germany.
⁸⁶ Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.
⁸⁷ Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA.
⁸⁸ Department of Psychiatry, University of California, San Francisco, CA, USA.
⁸⁹ Department of Cell Systems & Anatomy, The University of Texas Health Science Center, San Antonio, TX, USA.
⁹⁰ Glenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases, University of Texas, San Antonio, TX, USA.
⁹¹ University of Texas Health Sciences Center, Houston, NA, US.
⁹² National Ageing Research Institute, Parkville, Melbourne, VIC, Australia.
⁹³ University of Melbourne, Academic Unit for Psychiatry of Old Age, St George's Hospital, Melbourne, VIC, Australia.
⁹⁴ Dementia Collaborative Research Centre, University of New South Wales, Sydney, NSW, Australia.
⁹⁵ Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, USA.
⁹⁶ Harvard Medical School, Boston, MA, USA.
⁹⁷ MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
⁹⁸ Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands.
⁹⁹ Hofstra Northwell School of Medicine, Hempstead, NY, USA.
¹⁰⁰ Food and Drug Administration, Washington, DC, USA.
¹⁰¹ Analytic and Translational Genetics Unit, Department of Medicine, Department of Neurology and Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.
¹⁰² The Stanley Center for Psychiatric Research and Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
¹⁰³ Department of Epidemiology and Department of Health Services, University of Washington, Seattle, WA, USA.
¹⁰⁴ Kaiser Permanente Washington Heath Research Institute, Seattle, WA, USA.
¹⁰⁵ Institute of Social Medicine, Occupational Health and Public Health, University of Leipzig, Leipzig, Germany.
¹⁰⁶ Institute of Primary Medical Care, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
¹⁰⁷ Neuroscience Research Australia, Randwick, NSW, Australia.
¹⁰⁸ Kaiser Permanente Northern California, Division of Research, Oakland, CA, USA.
¹⁰⁹ Alzheimer Scotland Dementia Research Centre, University of Edinburgh, Edinburgh, UK.
¹¹⁰ Department of Developmental Disability Neuropsychiatry, School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia.
¹¹¹ Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia.
¹¹² Centre for Advanced Imaging, The University of Queensland, Brisbane, QLD, Australia.
¹¹³ Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
¹¹⁴ Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
¹¹⁵ McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
¹¹⁶ Inserm, Bordeaux Population Health Research Center, team VINTAGE, UMR 1219, University of Bordeaux, Bordeaux, France.
¹¹⁷ Bordeaux University Hospital (CHU Bordeaux), Department of Neurology, Bordeaux, France.
¹¹⁸ Folkhälsan Research Center, Helsinki, Finland.
¹¹⁹ Department of General Practice and Primary Health Care, University of Helsinki, and Helsinki University Hospital, University of Helsinki, Helsinki, Finland.
¹²⁰ Department of Obstetrics & Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Helsinki, Singapore.
¹²¹ Department of Medicine, Division of Geriatrics, University of Mississippi Medical Center, Jackson, MS, USA.
¹²² Laboratory of Epidemiology and Population Sciences, National Institute on Aging, Intramural Research Program, National Institutes of Health, Bethesda, MD, USA.
¹²³ Department of Public Health, Oxford University, Oxford, UK.

PMID: 35974141
PMCID: PMC9734053
DOI: 10.1038/s41380-022-01710-8

Genome-wide meta-analyses reveal novel loci for verbal short-term memory and learning

Jari Lahti et al. Mol Psychiatry. 2022 Nov.

. 2022 Nov;27(11):4419-4431.

doi: 10.1038/s41380-022-01710-8. Epub 2022 Aug 16.

Authors

Affiliations

¹ Department of Psychology and Logopedics, University of Helsinki, Helsinki, Finland. jari.lahti@helsinki.fi.
² Turku Institute of Advanced Studies, University of Turku, Turku, Finland. jari.lahti@helsinki.fi.
³ Department of Psychology and Logopedics, University of Helsinki, Helsinki, Finland.
⁴ Department of Biostatistics, Boston University, Boston, MA, USA.
⁵ Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA.
⁶ Department of Basic Medical Science, Neuroscience, and Sense Organs, University of Bari Aldo Moro, Bari, Italy.
⁷ Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
⁸ Department of Mathematics and Statistics, Murdoch University, Murdoch, WA, Australia.
⁹ Framingham Heart Study, Framingham, MA, USA.
¹⁰ Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany.
¹¹ German Center for Neurodegenerative Diseases, Bonn, Germany.
¹² Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.
¹³ Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX, USA.
¹⁴ Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.
¹⁵ Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
¹⁶ Usher Institute, University of Edinburgh, Edinburgh, UK.
¹⁷ Centre for Global Health Research, Usher Institute, University of Edinburgh, Edinburgh, UK.
¹⁸ Department of Psychology, Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.
¹⁹ Center for Translational and Computational Neuroimmunology, Columbia University Medical Center, New York, NY, USA.
²⁰ Translational Neurogenomics Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
²¹ Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI, USA.
²² Department of Family Medicine, University of Washington, Seattle, WA, USA.
²³ Department of Epidemiology, University of Washington, Seattle, WA, USA.
²⁴ Department of Global Health, University of Washington, Seattle, WA, USA.
²⁵ Institute of Public Health Genetics, University of Washington, Seattle, WA, USA.
²⁶ Robertson Center for Biostatistics, University of Glasgow, Glasgow, UK.
²⁷ McGovern Medical School, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA.
²⁸ Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
²⁹ German Center for Neurodegenerative Diseases, Greifswald, Germany.
³⁰ Channing Laboratory, Brigham and Women's Hospital, Boston, MA, USA.
³¹ Harvard School of Public Health, Boston, MA, USA.
³² Icelandic Heart Assocation, Kopavogur, Iceland.
³³ Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
³⁴ Translational Gerontology Branch, National Institute on Aging, Intramural Research Program, National Institutes of Health, Baltimore, MD, USA.
³⁵ School of Medicine and Public Health, University of Newcastle, Callaghan, NSW, Australia.
³⁶ Institute of Social and Preventive Medicine, University of Lausanne, Lausanne, Switzerland.
³⁷ National Institute for Health and Welfare, Helsinki and Oulu, Oulu, Finland.
³⁸ Hospital for Children and Adolescents, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
³⁹ PEDEGO Research Unit, MRC Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland.
⁴⁰ Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
⁴¹ Department of Public Health, University of Helsinki, Helsinki, Finland.
⁴² Department for Neurodegenerative Diseases and Geriatric Psychiatry, University of Bonn, Bonn, Germany.
⁴³ Centre for Healthy Brain Ageing (CHeBA), School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia.
⁴⁴ Neuropsychiatric Institute, Prince of Wales Hospital, Sydney, NSW, Australia.
⁴⁵ Brain and Mind Centre, The University of Sydney, Sydney, NSW, Australia.
⁴⁶ School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia.
⁴⁷ Department of Psychiatry, University of Cologne, Cologne, Germany.
⁴⁸ Psychiatry Research, Zucker Hillside Hospital, Glen Oaks, NY, USA.
⁴⁹ Stanley Center for Psychiatric Research, Broad Institute, Cambridge, MA, USA.
⁵⁰ Helsinki Biobank, University of Helsinki Central Hospital, Helsinki, Finland.
⁵¹ Department of Economic and Social Sciences & Institute of Social Medicine, Rehabilitation Sciences and Healthcare Research, University of Applied Sciences Nordhausen, Nordhausen, Germany.
⁵² University of Leipzig, Leipzig, Germany.
⁵³ LIFE Leipzig Research Center for Civilization Diseases, Leipzig, Germany.
⁵⁴ Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.
⁵⁵ Sunnybrook Health Sciences Centre, University of Toronto, Randwick, NSW, Australia.
⁵⁶ QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
⁵⁷ Department of Neurology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada.
⁵⁸ Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD, USA.
⁵⁹ Data Tecnica International, Glen Echo, MD, USA.
⁶⁰ Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, USA.
⁶¹ Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN, USA.
⁶² Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indianapolis, IN, USA.
⁶³ Clinical Research Design, IT and Statistical Support Unit, Hunter Medical Research Institute, New Lambton, NSW, Australia.
⁶⁴ Department of Developmental Disability Neuropsychiatry, School of Psychiatry, University of New South Wales, Sydney, NSW, Australia.
⁶⁵ Department of Psychological & Brain Sciences, Indiana University Bloomington, Bloomington, IN, USA.
⁶⁶ Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.
⁶⁷ LIFE Research Center for Civilization Diseases, University of Leipzig, Leipzig, Germany.
⁶⁸ Department of Neurology, Boston University, Boston, MA, USA.
⁶⁹ Glenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases, University of Texas Health Sciences Center, San Antonio, TX, USA.
⁷⁰ Neuropsychiatry Service, Hunter New England Local Health District, Charlestown, NSW, Australia.
⁷¹ Centre for Cardiovascular Sciences, Queen's Medical Research Institute, Royal Infirmary of Edinburgh, University of Edinburgh, Edinburgh, UK.
⁷² School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, NSW, Australia.
⁷³ Hunter Medical Research Institute, New Lambton, NSW, Australia.
⁷⁴ Department of Data Science, University of Mississippi Medical Center, Jackson, MS, USA.
⁷⁵ Department of Epidemiology, University of Michigan, Ann Arbor, MI, USA.
⁷⁶ Institute of Social Research, Survey Research Center, University of Michigan, Ann Arbor, MI, USA.
⁷⁷ Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
⁷⁸ Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
⁷⁹ Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
⁸⁰ Section of Gerontology and Geriatrics, Department of Internal Medicine, Leiden University Medical Center, Leiden, The Netherlands.
⁸¹ Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA.
⁸² Department of Neurology and Alzheimer Center, VU University Medical Center, Amsterdam, The Netherlands.
⁸³ Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany.
⁸⁴ Day Clinic for Cognitive Neurology, University Hospital Leipzig, Leipzig, Germany.
⁸⁵ Interfaculty Institute for Genetics and Functional Genomics, Department Functional Genomics, University Medicine Greifswald, Greifswald, Germany.
⁸⁶ Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.
⁸⁷ Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA.
⁸⁸ Department of Psychiatry, University of California, San Francisco, CA, USA.
⁸⁹ Department of Cell Systems & Anatomy, The University of Texas Health Science Center, San Antonio, TX, USA.
⁹⁰ Glenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases, University of Texas, San Antonio, TX, USA.
⁹¹ University of Texas Health Sciences Center, Houston, NA, US.
⁹² National Ageing Research Institute, Parkville, Melbourne, VIC, Australia.
⁹³ University of Melbourne, Academic Unit for Psychiatry of Old Age, St George's Hospital, Melbourne, VIC, Australia.
⁹⁴ Dementia Collaborative Research Centre, University of New South Wales, Sydney, NSW, Australia.
⁹⁵ Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, USA.
⁹⁶ Harvard Medical School, Boston, MA, USA.
⁹⁷ MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
⁹⁸ Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands.
⁹⁹ Hofstra Northwell School of Medicine, Hempstead, NY, USA.
¹⁰⁰ Food and Drug Administration, Washington, DC, USA.
¹⁰¹ Analytic and Translational Genetics Unit, Department of Medicine, Department of Neurology and Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.
¹⁰² The Stanley Center for Psychiatric Research and Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
¹⁰³ Department of Epidemiology and Department of Health Services, University of Washington, Seattle, WA, USA.
¹⁰⁴ Kaiser Permanente Washington Heath Research Institute, Seattle, WA, USA.
¹⁰⁵ Institute of Social Medicine, Occupational Health and Public Health, University of Leipzig, Leipzig, Germany.
¹⁰⁶ Institute of Primary Medical Care, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
¹⁰⁷ Neuroscience Research Australia, Randwick, NSW, Australia.
¹⁰⁸ Kaiser Permanente Northern California, Division of Research, Oakland, CA, USA.
¹⁰⁹ Alzheimer Scotland Dementia Research Centre, University of Edinburgh, Edinburgh, UK.
¹¹⁰ Department of Developmental Disability Neuropsychiatry, School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia.
¹¹¹ Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia.
¹¹² Centre for Advanced Imaging, The University of Queensland, Brisbane, QLD, Australia.
¹¹³ Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
¹¹⁴ Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
¹¹⁵ McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
¹¹⁶ Inserm, Bordeaux Population Health Research Center, team VINTAGE, UMR 1219, University of Bordeaux, Bordeaux, France.
¹¹⁷ Bordeaux University Hospital (CHU Bordeaux), Department of Neurology, Bordeaux, France.
¹¹⁸ Folkhälsan Research Center, Helsinki, Finland.
¹¹⁹ Department of General Practice and Primary Health Care, University of Helsinki, and Helsinki University Hospital, University of Helsinki, Helsinki, Finland.
¹²⁰ Department of Obstetrics & Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Helsinki, Singapore.
¹²¹ Department of Medicine, Division of Geriatrics, University of Mississippi Medical Center, Jackson, MS, USA.
¹²² Laboratory of Epidemiology and Population Sciences, National Institute on Aging, Intramural Research Program, National Institutes of Health, Bethesda, MD, USA.
¹²³ Department of Public Health, Oxford University, Oxford, UK.

PMID: 35974141
PMCID: PMC9734053
DOI: 10.1038/s41380-022-01710-8

Abstract

Understanding the genomic basis of memory processes may help in combating neurodegenerative disorders. Hence, we examined the associations of common genetic variants with verbal short-term memory and verbal learning in adults without dementia or stroke (N = 53,637). We identified novel loci in the intronic region of CDH18, and at 13q21 and 3p21.1, as well as an expected signal in the APOE/APOC1/TOMM40 region. These results replicated in an independent sample. Functional and bioinformatic analyses supported many of these loci and further implicated POC1. We showed that polygenic score for verbal learning associated with brain activation in right parieto-occipital region during working memory task. Finally, we showed genetic correlations of these memory traits with several neurocognitive and health outcomes. Our findings suggest a role of several genomic loci in verbal memory processes.

PubMed Disclaimer

Conflict of interest statement

HB is in an Advisory Board member in Nutricia; HJG reported Fresenius Medical Care, BMP serves on the DSMB of a clinical trial funded by Zoll LifeCor and on the Steering Committee of the Yale Open Data Access Project funded by Johnson & Johnson. The remaining authors declare no competing interests.

Figures

**Fig. 1. Regional plot of associations of SNPs at the 5p14.3 region with verbal short-term memory in the discovery sample (N = 44,874).**
Dots indicate p-values of SNPs and rs425724 in an intron of *CDH18* is marked in violet.

**Fig. 2**
Regional plot of associations of SNPs at the 3q21 region with verbal learning in the discovery sample (N = 28,909; Upper panel). Dots indicate p-values of SNPs and the top lead SNP rs4687625 is marked in violet and another independent and significant SNP rs2276816 is marked in red. Lower panel indicates 15-core chromatin state in Roadmap brain-related tissues (E053-E082) and E125 ENCODE NH-A Astrocytes primary cells and shows that both significant SNPs are in transcriptionally active region.

**Fig. 3**
Regional plot of associations of SNPs at the 19q13.3 region with verbal learning (Upper panel). Dots indicate p values of SNPs and the top lead SNP rs4420638 is marked in violet and another independent and significant SNP rs6857 is marked in red. Lower panel indicates 15-core chromatin state in Roadmap brain-related tissues (E053-E082) and E125 ENCODE NH-A Astrocytes primary cells and shows that both significant SNPs are in or flanking transcriptionally active region.

Fig. 4. Associations of the polygenic score for verbal learning (PGS_VL) with activation in the right BA19 during the 2-back working memory task in a sample of N = 435 healthy adults (upper panel left view and lower panel right view).
Results are thresholded at peak-level p < 0.001 and masked for significantly increased activity during 2-back relative to 0-back. Rendered image illustrates clusters in which activity is negatively correlated with the PGS_VL (the right cluster survives correction for multiple comparisons at BA19; MNI coordinates x = 45, y = −64, Z = 10; FWE corrected p = 0.016). Left in the figure is left in the brain.

**Fig. 5**
Forest plot of genetic correlations between verbal short-term memory and 46 traits related to cognitive abilities or health (Genetic correlation [95% confidence interval]; significant genetic correlations after FDR correction in boldface).

**Fig. 6**
Forest plot of genetic correlations between verbal learning and 46 traits related to cognitive abilities or health (Genetic correlation [95% confidence interval]; significant genetic correlations after FDR correction in boldface).

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Genome-wide meta-analyses reveal novel loci for verbal short-term memory and learning

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Genome-wide meta-analyses reveal novel loci for verbal short-term memory and learning

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