Polygenic Scores for Major Depressive Disorder and Risk of Alcohol Dependence

John Kramer; Samuel Kuperman; Howard J Edenberg; John I Nurnberger Jr; John P Rice; Jay A Tischfield; Alison Goate; Tatiana M Foroud; Jacquelyn L Meyers; Bernice Porjesz; Danielle M Dick; Victor Hesselbrock; Eric Boerwinkle; Steven M Southwick; Allan M Andersen; John H Krystal; Robert H Pietrzak; Myrna M Weissman; Henry R Kranzler; Douglas F Levinson; Li Ma; James B Potash; Hang Zhou; Joel Gelernter; Xiaoming Liu; Shizhong Han

doi:10.1001/jamapsychiatry.2017.2269

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Polygenic Scores for Major Depressive Disorder and Risk of Alcohol Dependence

Journal article

Peer reviewed

Polygenic Scores for Major Depressive Disorder and Risk of Alcohol Dependence

John Kramer, Samuel Kuperman, Howard J Edenberg, John I Nurnberger Jr, John P Rice, Jay A Tischfield, Alison Goate, Tatiana M Foroud, Jacquelyn L Meyers, Bernice Porjesz, …

JAMA psychiatry (Chicago, Ill.), Vol.74(11), pp.1153-1160

11/01/2017

DOI: 10.1001/jamapsychiatry.2017.2269

PMCID: PMC5710224

PMID: 28813562

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Abstract

Major depressive disorder (MDD) and alcohol dependence (AD) are heritable disorders with significant public health burdens, and they are frequently comorbid. Common genetic factors that influence the co-occurrence of MDD and AD have been sought in family, twin, and adoption studies, and results to date have been promising but inconclusive. To examine whether AD and MDD overlap genetically, using a polygenic score approach. Association analyses were conducted between MDD polygenic risk score (PRS) and AD case-control status in European ancestry samples from 4 independent genome-wide association study (GWAS) data sets: the Collaborative Study on the Genetics of Alcoholism (COGA); the Study of Addiction, Genetics, and Environment (SAGE); the Yale-Penn genetic study of substance dependence; and the National Health and Resilience in Veterans Study (NHRVS). Results from a meta-analysis of MDD (9240 patients with MDD and 9519 controls) from the Psychiatric Genomics Consortium were applied to calculate PRS at thresholds from P < .05 to P ≤ .99 in each AD GWAS data set. Association between MDD PRS and AD. Participants analyzed included 788 cases (548 [69.5%] men; mean [SD] age, 38.2 [10.8] years) and 522 controls (151 [28.9.%] men; age [SD], 43.9 [11.6] years) from COGA; 631 cases (333 [52.8%] men; age [SD], 35.0 [7.7] years) and 756 controls (260 [34.4%] male; age [SD] 36.1 [7.7] years) from SAGE; 2135 cases (1375 [64.4%] men; age [SD], 39.4 [11.5] years) and 350 controls (126 [36.0%] men; age [SD], 43.5 [13.9] years) from Yale-Penn; and 317 cases (295 [93.1%] men; age [SD], 59.1 [13.1] years) and 1719 controls (1545 [89.9%] men; age [SD], 64.5 [13.3] years) from NHRVS. Higher MDD PRS was associated with a significantly increased risk of AD in all samples (COGA: best P = 1.7 × 10-6, R2 = 0.026; SAGE: best P = .001, R2 = 0.01; Yale-Penn: best P = .035, R2 = 0.0018; and NHRVS: best P = .004, R2 = 0.0074), with stronger evidence for association after meta-analysis of the 4 samples (best P = 3.3 × 10-9). In analyses adjusted for MDD status in 3 AD GWAS data sets, similar patterns of association were observed (COGA: best P = 7.6 × 10-6, R2 = 0.023; Yale-Penn: best P = .08, R2 = 0.0013; and NHRVS: best P = .006, R2 = 0.0072). After recalculating MDD PRS using MDD GWAS data sets without comorbid MDD-AD cases, significant evidence was observed for an association between the MDD PRS and AD in the meta-analysis of 3 GWAS AD samples without MDD cases (best P = .007). These results suggest that shared genetic susceptibility contributes modestly to MDD and AD comorbidity. Individuals with elevated polygenic risk for MDD may also be at risk for AD.

Comorbidity

Adult

Alcoholism - epidemiology

Alcoholism - genetics

Depressive Disorder, Major - epidemiology

Depressive Disorder, Major - genetics

European Continental Ancestry Group - genetics

Female

Genetic Predisposition to Disease - genetics

Genome-Wide Association Study

Humans

Male

Middle Aged

Multifactorial Inheritance

United States - epidemiology

Details

Title: Subtitle: Polygenic Scores for Major Depressive Disorder and Risk of Alcohol Dependence
Creators: John Kramer - University of Iowa
Samuel Kuperman - University of Iowa
Howard J Edenberg - Indiana University
John I Nurnberger Jr - Indiana University
John P Rice - Washington University in St. Louis
Jay A Tischfield - Rutgers, The State University of New Jersey
Alison Goate - Icahn School of Medicine at Mount Sinai
Tatiana M Foroud - Indiana University
Jacquelyn L Meyers - SUNY Downstate Health Sciences University
Bernice Porjesz - SUNY Downstate Health Sciences University
Danielle M Dick - Virginia Commonwealth University
Victor Hesselbrock - University of Connecticut
Eric Boerwinkle - The University of Texas Health Science Center at Houston
Steven M Southwick - Yale University
Allan M Andersen - University of Iowa
John H Krystal - Yale University
Robert H Pietrzak - Yale University
Myrna M Weissman - Columbia University
Henry R Kranzler - University of Pennsylvania
Douglas F Levinson - Stanford University
Li Ma - University of Maryland, College Park
James B Potash - University of Iowa
Hang Zhou - Yale University
Joel Gelernter - Yale University
Xiaoming Liu - The University of Texas Health Science Center at Houston
Shizhong Han - Johns Hopkins University
Resource Type: Journal article
Publication Details: JAMA psychiatry (Chicago, Ill.), Vol.74(11), pp.1153-1160
DOI: 10.1001/jamapsychiatry.2017.2269
PMID: 28813562
PMCID: PMC5710224
NLM abbreviation: JAMA Psychiatry
ISSN: 2168-622X
eISSN: 2168-6238
Grant note: K12 DA000357 / NIDA NIH HHS R01 AA024486 / NIAAA NIH HHS UL1 TR001863 / NCATS NIH HHS K01 DA037914 / NIDA NIH HHS P50 AG005138 / NIA NIH HHS R01 AA022994 / NIAAA NIH HHS
Language: English
Date published: 11/01/2017
Academic Unit: Psychiatry
Record Identifier: 9984280864902771

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