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
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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.
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