Dataset Information

Polygenic Scores for Major Depressive Disorder and Risk of Alcohol Dependence.

ABSTRACT:

Importance

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.

Objective

To examine whether AD and MDD overlap genetically, using a polygenic score approach.

Design, settings, and participants

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?Main outcomes and measuresAssociation between MDD PRS and AD.

Results

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).

Conclusions and relevance

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.

SUBMITTER: Andersen AM

PROVIDER: S-EPMC5710224 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Polygenic Scores for Major Depressive Disorder and Risk of Alcohol Dependence.

Andersen Allan M AM Pietrzak Robert H RH Kranzler Henry R HR Ma Li L Zhou Hang H Liu Xiaoming X Kramer John J Kuperman Samuel S Edenberg Howard J HJ Nurnberger John I JI Rice John P JP Tischfield Jay A JA Goate Alison A Foroud Tatiana M TM Meyers Jacquelyn L JL Porjesz Bernice B Dick Danielle M DM Hesselbrock Victor V Boerwinkle Eric E Southwick Steven M SM Krystal John H JH Weissman Myrna M MM Levinson Douglas F DF Potash James B JB Gelernter Joel J Han Shizhong S

JAMA psychiatry 20171101 11

<h4>Importance</h4>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.<h4>Objective</h4>To examine whether AD and MDD overlap genetically, using a polygenic score approach.<h4>Design, settings, and participants ...[more]

PMID: 28813562

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Project description:BackgroundEarly identification of individuals at high risk for alcohol use disorder (AUD) coupled with prompt interventions could reduce the incidence of AUD. In this study, we investigated whether Polygenic Risk Scores (PRS) can be used to evaluate the risk for AUD and AUD severity (as measured by the number of DSM-5 AUD diagnostic criteria met) and compared their performance with a measure of family history of AUD.MethodsWe studied individuals of European ancestry from the Collaborative Study on the Genetics of Alcoholism (COGA). DSM-5 diagnostic criteria were available for 7203 individuals, of whom 3451 met criteria for DSM-IV alcohol dependence or DSM-5 AUD and 1616 were alcohol-exposed controls aged ≥21 years with no history of AUD or drug dependence. Further, 4842 individuals had a positive first-degree family history of AUD (FH+), 2722 had an unknown family history (FH?), and 336 had a negative family history (FH-). PRS were derived from a meta-analysis of a genome-wide association study of AUD from the Million Veteran Program and scores from the problem subscale of the Alcohol Use Disorders Identification Test in the UK Biobank. We used mixed models to test the association between PRS and risk for AUD and AUD severity.ResultsAUD cases had higher PRS than controls with PRS increasing as the number of DSM-5 diagnostic criteria increased (p-values ≤ 1.85E-05 ) in the full COGA sample, the FH+ subsample, and the FH? subsample. Individuals in the top decile of PRS had odds ratios (OR) for developing AUD of 1.96 (95% CI: 1.54 to 2.51, p-value = 7.57E-08 ) and 1.86 (95% CI: 1.35 to 2.56, p-value = 1.32E-04 ) in the full sample and the FH+ subsample, respectively. These values are comparable to previously reported ORs for a first-degree family history (1.91 to 2.38) estimated from national surveys. PRS were also significantly associated with the DSM-5 AUD diagnostic criterion count in the full sample, the FH+ subsample, and the FH? subsample (p-values ≤6.7E-11 ). PRS remained significantly associated with AUD and AUD severity after accounting for a family history of AUD (p-values ≤6.8E-10 ).ConclusionsBoth PRS and family history were associated with AUD and AUD severity, indicating that these risk measures assess distinct aspects of liability to AUD traits.

Dataset Information

Polygenic Scores for Major Depressive Disorder and Risk of Alcohol Dependence.

Importance

Objective

Design, settings, and participants

Results

Conclusions and relevance

Publications

Polygenic Scores for Major Depressive Disorder and Risk of Alcohol Dependence.

Similar Datasets

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