Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
30929657
TITLE
Evidence of causal effect of major depression on alcohol dependence: findings from the psychiatric genomics consortium.
ABSTRACT
BACKGROUND NlmCategory: BACKGROUND
Despite established clinical associations among major depression (MD), alcohol dependence (AD), and alcohol consumption (AC), the nature of the causal relationship between them is not completely understood. We leveraged genome-wide data from the Psychiatric Genomics Consortium (PGC) and UK Biobank to test for the presence of shared genetic mechanisms and causal relationships among MD, AD, and AC.
METHODS NlmCategory: METHODS
Despite established clinical associations among major depression (MD), alcohol dependence (AD), and alcohol consumption (AC), the nature of the causal relationship between them is not completely understood. We leveraged genome-wide data from the Psychiatric Genomics Consortium (PGC) and UK Biobank to test for the presence of shared genetic mechanisms and causal relationships among MD, AD, and AC. Linkage disequilibrium score regression and Mendelian randomization (MR) were performed using genome-wide data from the PGC (MD: 135 458 cases and 344 901 controls; AD: 10 206 cases and 28 480 controls) and UK Biobank (AC-frequency: 438 308 individuals; AC-quantity: 307 098 individuals).
RESULTS NlmCategory: RESULTS
Despite established clinical associations among major depression (MD), alcohol dependence (AD), and alcohol consumption (AC), the nature of the causal relationship between them is not completely understood. We leveraged genome-wide data from the Psychiatric Genomics Consortium (PGC) and UK Biobank to test for the presence of shared genetic mechanisms and causal relationships among MD, AD, and AC. Linkage disequilibrium score regression and Mendelian randomization (MR) were performed using genome-wide data from the PGC (MD: 135 458 cases and 344 901 controls; AD: 10 206 cases and 28 480 controls) and UK Biobank (AC-frequency: 438 308 individuals; AC-quantity: 307 098 individuals). Positive genetic correlation was observed between MD and AD (rgMD-AD = + 0.47, P = 6.6 × 10-10). AC-quantity showed positive genetic correlation with both AD (rgAD-AC quantity = + 0.75, P = 1.8 × 10-14) and MD (rgMD-AC quantity = + 0.14, P = 2.9 × 10-7), while there was negative correlation of AC-frequency with MD (rgMD-AC frequency = -0.17, P = 1.5 × 10-10) and a non-significant result with AD. MR analyses confirmed the presence of pleiotropy among these four traits. However, the MD-AD results reflect a mediated-pleiotropy mechanism (i.e. causal relationship) with an effect of MD on AD (beta = 0.28, P = 1.29 × 10-6). There was no evidence for reverse causation.
CONCLUSION NlmCategory: CONCLUSIONS
Despite established clinical associations among major depression (MD), alcohol dependence (AD), and alcohol consumption (AC), the nature of the causal relationship between them is not completely understood. We leveraged genome-wide data from the Psychiatric Genomics Consortium (PGC) and UK Biobank to test for the presence of shared genetic mechanisms and causal relationships among MD, AD, and AC. Linkage disequilibrium score regression and Mendelian randomization (MR) were performed using genome-wide data from the PGC (MD: 135 458 cases and 344 901 controls; AD: 10 206 cases and 28 480 controls) and UK Biobank (AC-frequency: 438 308 individuals; AC-quantity: 307 098 individuals). Positive genetic correlation was observed between MD and AD (rgMD-AD = + 0.47, P = 6.6 × 10-10). AC-quantity showed positive genetic correlation with both AD (rgAD-AC quantity = + 0.75, P = 1.8 × 10-14) and MD (rgMD-AC quantity = + 0.14, P = 2.9 × 10-7), while there was negative correlation of AC-frequency with MD (rgMD-AC frequency = -0.17, P = 1.5 × 10-10) and a non-significant result with AD. MR analyses confirmed the presence of pleiotropy among these four traits. However, the MD-AD results reflect a mediated-pleiotropy mechanism (i.e. causal relationship) with an effect of MD on AD (beta = 0.28, P = 1.29 × 10-6). There was no evidence for reverse causation. This study supports a causal role for genetic liability of MD on AD based on genetic datasets including thousands of individuals. Understanding mechanisms underlying MD-AD comorbidity addresses important public health concerns and has the potential to facilitate prevention and intervention efforts.
DATE PUBLISHED
2019 Apr 01
HISTORY
PUBSTATUS PUBSTATUSDATE
entrez 2019/04/02 06:00
pubmed 2019/04/02 06:00
medline 2019/04/02 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Polimanti R Polimanti Renato R Department of Psychiatry,Yale University School of Medicine and VA CT Healthcare Center,West Haven, Connecticut,USA.
Peterson RE Peterson Roseann E RE Department of Psychiatry,Virginia Institute for Psychiatric and Behavioral Genetics,Virginia Commonwealth University, Richmond, Virginia,USA.
Ong JS Ong Jue-Sheng JS Statistical Genetics,QIMR Berghofer, Brisbane,Australia.
MacGregor S MacGregor Stuart S Statistical Genetics,QIMR Berghofer, Brisbane,Australia.
Edwards AC Edwards Alexis C AC Department of Psychiatry,Virginia Institute for Psychiatric and Behavioral Genetics,Virginia Commonwealth University, Richmond, Virginia,USA.
Clarke TK Clarke Toni-Kim TK Division of Psychiatry,University of Edinburgh,Edinburgh,UK.
Frank J Frank Josef J Department of Genetic Epidemiology in Psychiatry,Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University,Mannheim, Baden-Württemberg,Germany.
Gerring Z Gerring Zachary Z Translational Neurogenomics, QIMR Berghofer,Brisbane,Australia.
Gillespie NA Gillespie Nathan A NA Department of Psychiatry,Virginia Institute for Psychiatric and Behavioral Genetics,Virginia Commonwealth University, Richmond, Virginia,USA.
Lind PA Lind Penelope A PA Psychiatric Genetics, QIMR Berghofer,Brisbane,Australia.
Maes HH Maes Hermine H HH Department of Psychiatry,Virginia Institute for Psychiatric and Behavioral Genetics,Virginia Commonwealth University, Richmond, Virginia,USA.
Martin NG Martin Nicholas G NG Genetic Epidemiology, QIMR Berghofer,Brisbane,Australia.
Mbarek H Mbarek Hamdi H Department of Biological Psychology & EMGO + Institute for Health and Care Research,Vrije Universiteit Amsterdam, Amsterdam,the Netherlands.
Medland SE Medland Sarah E SE Psychiatric Genetics, QIMR Berghofer,Brisbane,Australia.
Streit F Streit Fabian F Department of Genetic Epidemiology in Psychiatry,Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University,Mannheim, Baden-Württemberg,Germany.
Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium
Agrawal A Agrawal Arpana A Department of Psychiatry,Washington University School of Medicine,Saint Louis, Missouri,USA.
Edenberg HJ Edenberg Howard J HJ Department of Biochemistry and Molecular Biology,Indiana University School of Medicine,Indianapolis, Indiana,USA.
Kendler KS Kendler Kenneth S KS Department of Psychiatry,Virginia Institute for Psychiatric and Behavioral Genetics,Virginia Commonwealth University, Richmond, Virginia,USA.
Lewis CM Lewis Cathryn M CM Social, Genetic and Developmental Psychiatry Centre,Institute of Psychiatry, Psychology & Neuroscience, King's CollegeLondon,UK.
Sullivan PF Sullivan Patrick F PF Department of Medical Epidemiology and Biostatistics,Karolinska Institutet,Stockholm,Sweden.
Wray NR Wray Naomi R NR Institute for Molecular Bioscience, The University of Queensland,Brisbane,Australia.
Gelernter J Gelernter Joel J Department of Psychiatry,Yale University School of Medicine and VA CT Healthcare Center,West Haven, Connecticut,USA.
Derks EM Derks Eske M EM Translational Neurogenomics, QIMR Berghofer,Brisbane,Australia.
INVESTIGATORS
JOURNAL
VOLUME:
ISSUE:
TITLE: Psychological medicine
ISOABBREVIATION: Psychol Med
YEAR: 2019
MONTH: Apr
DAY: 01
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1469-8978
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Psychol Med
COUNTRY: England
ISSNLINKING: 0033-2917
NLMUNIQUEID: 1254142
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
COMMENTS AND CORRECTIONS
GRANTS
GRANTID AGENCY COUNTRY
K01 MH113848 NIMH NIH HHS United States
GENERAL NOTE
KEYWORDS
KEYWORD
Alcohol consumption
Mendelian randomization
alcohol dependence
genetic correlation
genome-wide association
major depression
MESH HEADINGS
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's