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

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Genome-wide meta-analyses reveal novel loci for verbal short-term memory and learning
Molecular Psychiatry ( IF 9.6 ) Pub Date : 2022-08-16 , DOI: 10.1038/s41380-022-01710-8
Jari Lahti _{1,

2} , Samuli Tuominen ₁ , Qiong Yang ₃ , Giulio Pergola _{4,

5} , Shahzad Ahmad ₆ , Najaf Amin ₆ , Nicola J Armstrong ₇ , Alexa Beiser _{3,

8} , Katharina Bey _{9,

10} , Joshua C Bis ₁₁ , Eric Boerwinkle _{12,

13} , Jan Bressler ₁₂ , Archie Campbell _{14,

15} , Harry Campbell ₁₆ , Qiang Chen ₄ , Janie Corley ₁₇ , Simon R Cox ₁₇ , Gail Davies ₁₇ , Philip L De Jager ₁₈ , Eske M Derks ₁₉ , Jessica D Faul ₂₀ , Annette L Fitzpatrick _{21,

22,

23} , Alison E Fohner _{22,

24} , Ian Ford ₂₅ , Myriam Fornage ₂₆ , Zachary Gerring ₁₉ , Hans J Grabe _{27,

28} , Francine Grodstein _{29,

30} , Vilmundur Gudnason _{31,

32} , Eleanor Simonsick ₃₃ , Elizabeth G Holliday ₃₄ , Peter K Joshi _{16,

35} , Eero Kajantie _{36,

37,

38} , Jaakko Kaprio _{39,

40} , Pauliina Karell ₃₉ , Luca Kleineidam _{10,

41} , Maria J Knol ₆ , Nicole A Kochan _{42,

43} , John B Kwok _{44,

45} , Markus Leber ₄₆ , Max Lam _{47,

48} , Teresa Lee _{42,

43} , Shuo Li ₃ , Anu Loukola ₄₉ , Tobias Luck _{50,

51,

52} , Riccardo E Marioni _{14,

53} , Karen A Mather _{42,

54} , Sarah Medland ₅₅ , Saira S Mirza _{6,

56} , Mike A Nalls _{57,

58} , Kwangsik Nho _{59,

60,

61} , Adrienne O'Donnell _{3,

8} , Christopher Oldmeadow ₆₂ , Jodie Painter ₅₅ , Alison Pattie ₁₇ , Simone Reppermund _{42,

63} , Shannon L Risacher _{59,

61} , Richard J Rose ₆₄ , Vijay Sadashivaiah ₄ , Markus Scholz _{65,

66} , Claudia L Satizabal _{8,

67,

68} , Peter W Schofield ₆₉ , Katharina E Schraut _{16,

70} , Rodney J Scott _{71,

72} , Jeannette Simino ₇₃ , Albert V Smith _{31,

32} , Jennifer A Smith _{74,

75} , David J Stott ₇₆ , Ida Surakka ₇₇ , Alexander Teumer ₇₈ , Anbupalam Thalamuthu ₄₂ , Stella Trompet ₇₉ , Stephen T Turner ₈₀ , Sven J van der Lee _{6,

81} , Arno Villringer _{82,

83} , Uwe Völker ₈₄ , Robert S Wilson ₈₅ , Katharina Wittfeld _{27,

28} , Eero Vuoksimaa ₃₉ , Rui Xia ₈₆ , Kristine Yaffe ₈₇ , Lei Yu ₈₅ , Habil Zare _{88,

89,

90} , Wei Zhao ₇₄ , David Ames _{91,

92} , John Attia _{34,

62} , David A Bennett ₈₅ , Henry Brodaty _{42,

93} , Daniel I Chasman _{94,

95} , Aaron L Goldman ₄ , Caroline Hayward ₉₆ , M Arfan Ikram ₆ , J Wouter Jukema ₉₇ , Sharon L R Kardia ₇₄ , Todd Lencz ₉₈ , Markus Loeffler _{65,

66} , Venkata S Mattay _{4,

99} , Aarno Palotie _{39,

100,

101} , Bruce M Psaty _{11,

102,

103} , Alfredo Ramirez _{41,

46} , Paul M Ridker _{94,

95} , Steffi G Riedel-Heller ₁₀₄ , Perminder S Sachdev _{42,

43} , Andrew J Saykin _{59,

60,

61} , Martin Scherer ₁₀₅ , Peter R Schofield _{45,

106} , Stephen Sidney ₁₀₇ , John M Starr _{17,

108} , Julian Trollor _{42,

109} , William Ulrich ₄ , Michael Wagner _{10,

41} , David R Weir ₂₀ , James F Wilson _{16,

96} , Margaret J Wright _{110,

111} , Daniel R Weinberger _{4,

112,

113,

114} , Stephanie Debette _{115,

116} , Johan G Eriksson _{117,

118,

119} , Thomas H Mosley ₁₂₀ , Lenore J Launer ₁₂₁ , Cornelia M van Duijn _{6,

122} , Ian J Deary _{17,

53} , Sudha Seshadri _{8,

67,

68} , Katri Räikkönen ₁

Affiliation

Department of Psychology and Logopedics, University of Helsinki, Helsinki, Finland.
Turku Institute of Advanced Studies, University of Turku, Turku, Finland.
Department of Biostatistics, Boston University, Boston, MA, USA.
Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA.
Department of Basic Medical Science, Neuroscience, and Sense Organs, University of Bari Aldo Moro, Bari, Italy.
Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
Department of Mathematics and Statistics, Murdoch University, Murdoch, WA, Australia.
Framingham Heart Study, Framingham, MA, USA.
Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany.
German Center for Neurodegenerative Diseases, Bonn, Germany.
Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.
Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX, USA.
Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.
Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
Usher Institute, University of Edinburgh, Edinburgh, UK.
Centre for Global Health Research, Usher Institute, University of Edinburgh, Edinburgh, UK.
Department of Psychology, Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.
Center for Translational and Computational Neuroimmunology, Columbia University Medical Center, New York, NY, USA.
Translational Neurogenomics Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI, USA.
Department of Family Medicine, University of Washington, Seattle, WA, USA.
Department of Epidemiology, University of Washington, Seattle, WA, USA.
Department of Global Health, University of Washington, Seattle, WA, USA.
Institute of Public Health Genetics, University of Washington, Seattle, WA, USA.
Robertson Center for Biostatistics, University of Glasgow, Glasgow, UK.
McGovern Medical School, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA.
Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
German Center for Neurodegenerative Diseases, Greifswald, Germany.
Channing Laboratory, Brigham and Women's Hospital, Boston, MA, USA.
Harvard School of Public Health, Boston, MA, USA.
Icelandic Heart Assocation, Kopavogur, Iceland.
Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
Translational Gerontology Branch, National Institute on Aging, Intramural Research Program, National Institutes of Health, Baltimore, MD, USA.
School of Medicine and Public Health, University of Newcastle, Callaghan, NSW, Australia.
Institute of Social and Preventive Medicine, University of Lausanne, Lausanne, Switzerland.
National Institute for Health and Welfare, Helsinki and Oulu, Oulu, Finland.
Hospital for Children and Adolescents, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
PEDEGO Research Unit, MRC Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland.
Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
Department of Public Health, University of Helsinki, Helsinki, Finland.
Department for Neurodegenerative Diseases and Geriatric Psychiatry, University of Bonn, Bonn, Germany.
Centre for Healthy Brain Ageing (CHeBA), School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia.
Neuropsychiatric Institute, Prince of Wales Hospital, Sydney, NSW, Australia.
Brain and Mind Centre, The University of Sydney, Sydney, NSW, Australia.
School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia.
Department of Psychiatry, University of Cologne, Cologne, Germany.
Psychiatry Research, Zucker Hillside Hospital, Glen Oaks, NY, USA.
Stanley Center for Psychiatric Research, Broad Institute, Cambridge, MA, USA.
Helsinki Biobank, University of Helsinki Central Hospital, Helsinki, Finland.
Department of Economic and Social Sciences & Institute of Social Medicine, Rehabilitation Sciences and Healthcare Research, University of Applied Sciences Nordhausen, Nordhausen, Germany.
University of Leipzig, Leipzig, Germany.
LIFE Leipzig Research Center for Civilization Diseases, Leipzig, Germany.
Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.
Sunnybrook Health Sciences Centre, University of Toronto, Randwick, NSW, Australia.
QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
Department of Neurology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada.
Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD, USA.
Data Tecnica International, Glen Echo, MD, USA.
Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, USA.
Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN, USA.
Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indianapolis, IN, USA.
Clinical Research Design, IT and Statistical Support Unit, Hunter Medical Research Institute, New Lambton, NSW, Australia.
Department of Developmental Disability Neuropsychiatry, School of Psychiatry, University of New South Wales, Sydney, NSW, Australia.
Department of Psychological & Brain Sciences, Indiana University Bloomington, Bloomington, IN, USA.
Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.
LIFE Research Center for Civilization Diseases, University of Leipzig, Leipzig, Germany.
Department of Neurology, Boston University, Boston, MA, USA.
Glenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases, University of Texas Health Sciences Center, San Antonio, TX, USA.
Neuropsychiatry Service, Hunter New England Local Health District, Charlestown, NSW, Australia.
Centre for Cardiovascular Sciences, Queen's Medical Research Institute, Royal Infirmary of Edinburgh, University of Edinburgh, Edinburgh, UK.
School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, NSW, Australia.
Hunter Medical Research Institute, New Lambton, NSW, Australia.
Department of Data Science, University of Mississippi Medical Center, Jackson, MS, USA.
Department of Epidemiology, University of Michigan, Ann Arbor, MI, USA.
Institute of Social Research, Survey Research Center, University of Michigan, Ann Arbor, MI, USA.
Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
Section of Gerontology and Geriatrics, Department of Internal Medicine, Leiden University Medical Center, Leiden, The Netherlands.
Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA.
Department of Neurology and Alzheimer Center, VU University Medical Center, Amsterdam, The Netherlands.
Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany.
Day Clinic for Cognitive Neurology, University Hospital Leipzig, Leipzig, Germany.
Interfaculty Institute for Genetics and Functional Genomics, Department Functional Genomics, University Medicine Greifswald, Greifswald, Germany.
Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.
Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA.
Department of Psychiatry, University of California, San Francisco, CA, USA.
Department of Cell Systems & Anatomy, The University of Texas Health Science Center, San Antonio, TX, USA.
Glenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases, University of Texas, San Antonio, TX, USA.
University of Texas Health Sciences Center, Houston, NA, US.
National Ageing Research Institute, Parkville, Melbourne, VIC, Australia.
University of Melbourne, Academic Unit for Psychiatry of Old Age, St George's Hospital, Melbourne, VIC, Australia.
Dementia Collaborative Research Centre, University of New South Wales, Sydney, NSW, Australia.
Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Harvard Medical School, Boston, MA, USA.
MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands.
Hofstra Northwell School of Medicine, Hempstead, NY, USA.
Food and Drug Administration, Washington, DC, USA.
Analytic and Translational Genetics Unit, Department of Medicine, Department of Neurology and Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.
The Stanley Center for Psychiatric Research and Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Department of Epidemiology and Department of Health Services, University of Washington, Seattle, WA, USA.
Kaiser Permanente Washington Heath Research Institute, Seattle, WA, USA.
Institute of Social Medicine, Occupational Health and Public Health, University of Leipzig, Leipzig, Germany.
Institute of Primary Medical Care, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Neuroscience Research Australia, Randwick, NSW, Australia.
Kaiser Permanente Northern California, Division of Research, Oakland, CA, USA.
Alzheimer Scotland Dementia Research Centre, University of Edinburgh, Edinburgh, UK.
Department of Developmental Disability Neuropsychiatry, School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia.
Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia.
Centre for Advanced Imaging, The University of Queensland, Brisbane, QLD, Australia.
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Inserm, Bordeaux Population Health Research Center, team VINTAGE, UMR 1219, University of Bordeaux, Bordeaux, France.
Bordeaux University Hospital (CHU Bordeaux), Department of Neurology, Bordeaux, France.
Folkhälsan Research Center, Helsinki, Finland.
Department of General Practice and Primary Health Care, University of Helsinki, and Helsinki University Hospital, University of Helsinki, Helsinki, Finland.
Department of Obstetrics & Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Helsinki, Singapore.
Department of Medicine, Division of Geriatrics, University of Mississippi Medical Center, Jackson, MS, USA.
Laboratory of Epidemiology and Population Sciences, National Institute on Aging, Intramural Research Program, National Institutes of Health, Bethesda, MD, USA.
Department of Public Health, Oxford University, Oxford, UK.

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.

中文翻译：

全基因组荟萃分析揭示了言语短期记忆和学习的新位点

了解记忆过程的基因组基础可能有助于对抗神经退行性疾病。因此，我们在没有痴呆或中风的成年人中研究了常见遗传变异与言语短期记忆和言语学习的关联（ N = 53,637）。我们在CDH18的内含子区域以及 13q21 和 3p21.1 处鉴定了新的位点，以及APOE/APOC1/TOMM40区域中的预期信号。这些结果在独立样本中得到重复。功能和生物信息学分析支持其中许多位点并进一步暗示POC1 。我们表明，言语学习的多基因评分与工作记忆任务期间右顶枕区的大脑激活相关。最后，我们展示了这些记忆特征与几种神经认知和健康结果的遗传相关性。我们的研究结果表明了几个基因组位点在言语记忆过程中的作用。

更新日期：2022-08-16

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