A phenome-wide association and Mendelian Randomisation study of polygenic risk for depression in UK Biobank

被引：0

作者：

Xueyi Shen

David M. Howard

Mark J. Adams

W. David Hill

Toni-Kim Clarke

Ian J. Deary

Heather C. Whalley

Andrew M. McIntosh

机构：

[1] University of Edinburgh,Division of Psychiatry

[2] King’s College London,Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience

[3] University of Edinburgh,Centre for Cognitive Ageing and Cognitive Epidemiology

[4] University of Edinburgh,Department of Psychology

[5] The University of Queensland,Institute for Molecular Bioscience

[6] The University of Queensland,Queensland Brain Institute

[7] Massachusetts General Hospital,Analytic and Translational Genetics Unit

[8] Universitätsmedizin Berlin Campus Charité Mitte,Department of Psychiatry and Psychotherapy

[9] Broad Institute,Medical and Population Genetics

[10] University of Wurzburg,Department of Psychiatry, Psychosomatics and Psychotherapy

[11] Karolinska Institutet,Centre for Psychiatry Research, Department of Clinical Neuroscience

[12] Aarhus University,Department of Biomedicine

[13] Vrije Universiteit Amsterdam,Dept of Biological Psychology & EMGO+Institute for Health and Care Research

[14] Aarhus University,Centre for Integrated Register

[15] Aarhus University,based Research

[16] The Lundbeck Foundation Initiative for Integrative Psychiatric Research,National Centre for Register

[17] University of Adelaide,Based Research

[18] Max Planck Institute of Psychiatry,iPSYCH

[19] Technical University of Munich,Discipline of Psychiatry

[20] Virginia Commonwealth University,Department of Translational Research in Psychiatry

[21] Statens Serum Institut,Department of Neurology, Klinikum rechts der Isar

[22] Vrije Universiteit Medical Center and GGZ inGeest,Department of Psychiatry

[23] Virginia Institute for Psychiatric and Behavior Genetics,Center for Neonatal Screening, Department for Congenital Disorders

[24] Emory University School of Medicine,Department of Psychiatry

[25] Karolinska Institutet,Department of Psychiatry and Behavioral Sciences

[26] Aarhus University,Department of Medical Epidemiology and Biostatistics

[27] Aarhus University,Department of Clinical Medicine, Translational Neuropsychiatry Unit

[28] Wellcome Trust Sanger Institute,iSEQ, Centre for Integrative Sequencing

[29] European Bioinformatics Institute (EMBL-EBI),Human Genetics

[30] University Hospital of Lausanne,Statistical genomics and systems genetics

[31] QIMR Berghofer Medical Research Institute,Department of Psychiatry

[32] The University of Queensland,Genetics and Computational Biology

[33] Cardiff University,Centre for Advanced Imaging

[34] Duke University,Psychological Medicine

[35] Duke University,Center for Genomic and Computational Biology

[36] University of Bonn,Department of Pediatrics, Division of Medical Genetics

[37] School of Medicine & University Hospital Bonn,Institute of Human Genetics

[38] Erasmus MC,Epidemiology

[39] Dokuz Eylul University School Of Medicine,Psychiatry

[40] Massachusetts General Hospital,Department of Psychiatry

[41] Massachusetts General Hospital,Psychiatric and Neurodevelopmental Genetics Unit (PNGU)

[42] Broad Institute,Stanley Center for Psychiatric Research

[43] Cardiff University,Neuroscience and Mental Health

[44] University of British Columbia,Bioinformatics

[45] Harvard T.H. Chan School of Public Health,Department of Epidemiology

[46] Massachusetts Institute of Technology,Department of Mathematics

[47] Heidelberg University,Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim

[48] University of Basel,Department of Psychiatry (UPK)

[49] University of Basel,Department of Biomedicine

[50] University of Marburg,Centre for Human Genetics

来源：

Nature Communications | / 11卷

关键词：

D O I：

暂无

中图分类号：

学科分类号：

摘要：

Depression is a leading cause of worldwide disability but there remains considerable uncertainty regarding its neural and behavioural associations. Here, using non-overlapping Psychiatric Genomics Consortium (PGC) datasets as a reference, we estimate polygenic risk scores for depression (depression-PRS) in a discovery (N = 10,674) and replication (N = 11,214) imaging sample from UK Biobank. We report 77 traits that are significantly associated with depression-PRS, in both discovery and replication analyses. Mendelian Randomisation analysis supports a potential causal effect of liability to depression on brain white matter microstructure (β: 0.125 to 0.868, pFDR < 0.043). Several behavioural traits are also associated with depression-PRS (β: 0.014 to 0.180, pFDR: 0.049 to 1.28 × 10−14) and we find a significant and positive interaction between depression-PRS and adverse environmental exposures on mental health outcomes. This study reveals replicable associations between depression-PRS and white matter microstructure. Our results indicate that white matter microstructure differences may be a causal consequence of liability to depression.

引用

共 50 条

[1] A PHENOME-WIDE ASSOCIATION AND MENDELIAN RANDOMISATION STUDY OF POLYGENIC RISK FOR DEPRESSION IN UK BIOBANK
Shen, Xueyi
Howard, David
Adams, Mark
Deary, Ian
Whalley, Heather
McIntosh, Andrew
EUROPEAN NEUROPSYCHOPHARMACOLOGY, 2019, 29 : S88 - S88
[2] A phenome-wide association and Mendelian Randomisation study of polygenic risk for depression in UK Biobank
Shen, Xueyi
Howard, David M.
Adams, Mark J.
Hill, W. David
Clarke, Toni-Kim
Deary, Ian J.
Whalley, Heather C.
Mclntosh, Andrew M.
NATURE COMMUNICATIONS, 2020, 11 (01)
[3] Association between habitual coffee consumption and multiple disease outcomes: A Mendelian randomisation phenome-wide association study in the UK Biobank
Nicolopoulos, Konstance
Mulugeta, Anwar
Zhou, Ang
Hypponen, Elina
CLINICAL NUTRITION, 2020, 39 (11) : 3467 - 3476
[4] Association between major depressive disorder and multiple disease outcomes: a phenome-wide Mendelian randomisation study in the UK Biobank
Mulugeta, Anwar
Zhou, Ang
King, Catherine
Hypponen, Elina
MOLECULAR PSYCHIATRY, 2020, 25 (07) : 1469 - 1476
[5] Association between major depressive disorder and multiple disease outcomes: a phenome-wide Mendelian randomisation study in the UK Biobank
Anwar Mulugeta
Ang Zhou
Catherine King
Elina Hyppönen
Molecular Psychiatry, 2020, 25 : 1469 - 1476
[6] A phenome-wide association study of polygenic scores for selected childhood cancer: Results from the UK Biobank
Jung, Eun Mi
Raduski, Andrew R.
Mills, Lauren J.
Spector, Logan G.
HUMAN GENETICS AND GENOMICS ADVANCES, 2025, 6 (01):
[7] A PHENOME-WIDE MENDELIAN RANDOMISATION STUDY FOR MAJOR DEPRESSIVE DISORDER
Shen, Xueyi
Choi, Karmel
Lin, Bochao
Adams, Mark
McIntosh, Andrew
EUROPEAN NEUROPSYCHOPHARMACOLOGY, 2022, 63 : E118 - E119
[8] Identifying potential causal effects of Parkinson's disease: A polygenic risk score-based phenome-wide association and mendelian randomization study in UK Biobank
Shi, Changhe
Ma, Dongrui
Li, Mengjie
Wang, Zhiyun
Hao, Chenwei
Liang, Yuanyuan
Feng, Yanmei
Hu, Zhengwei
Hao, Xiaoyan
Guo, Mengnan
Li, Shuangjie
Zuo, Chunyan
Sun, Yuemeng
Tang, Mibo
Mao, Chengyuan
Zhang, Chan
Xu, Yuming
Sun, Shilei
NPJ PARKINSONS DISEASE, 2024, 10 (01)
[9] Searching for causal relationships of glioma: a phenome-wide Mendelian randomisation study
Charlie N. Saunders
Alex J. Cornish
Ben Kinnersley
Philip J. Law
Richard S. Houlston
British Journal of Cancer, 2021, 124 : 447 - 454
[10] Searching for causal relationships of glioma: a phenome-wide Mendelian randomisation study
Saunders, Charlie N.
Cornish, Alex J.
Kinnersley, Ben
Law, Philip J.
Houlston, Richard S.
Claus, Elizabeth B.
Il'yasova, Dora
Schildkraut, Joellen
Barnholtz-Sloan, Jill S.
Olson, Sara H.
Bernstein, Jonine L.
Lai, Rose K.
Chanock, Stephen
Rajaraman, Preetha
Johansen, Christoffer
Jenkins, Robert B.
Melin, Beatrice S.
Wrensch, Margaret R.
Sanson, Marc
Bondy, Melissa L.
BRITISH JOURNAL OF CANCER, 2021, 124 (02) : 447 - 454

← 1 2 3 4 5 →