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Evidence of causal effect of major depression on alcohol dependence: findings from the psychiatric genomics consortium.

Publication ,  Journal Article
Polimanti, R; Peterson, RE; Ong, J-S; MacGregor, S; Edwards, AC; Clarke, T-K; Frank, J; Gerring, Z; Gillespie, NA; Lind, PA; Maes, HH ...
Published in: Psychol Med
May 2019

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: 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: 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: 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.

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Published In

Psychol Med

DOI

EISSN

1469-8978

Publication Date

May 2019

Volume

49

Issue

7

Start / End Page

1218 / 1226

Location

England

Related Subject Headings

  • United Kingdom
  • Psychiatry
  • Middle Aged
  • Mendelian Randomization Analysis
  • Male
  • Linkage Disequilibrium
  • Humans
  • Genomics
  • Genome-Wide Association Study
  • Genetic Association Studies
 

Citation

APA
Chicago
ICMJE
MLA
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Polimanti, R., Peterson, R. E., Ong, J.-S., MacGregor, S., Edwards, A. C., Clarke, T.-K., … Derks, E. M. (2019). Evidence of causal effect of major depression on alcohol dependence: findings from the psychiatric genomics consortium. Psychol Med, 49(7), 1218–1226. https://doi.org/10.1017/S0033291719000667
Polimanti, Renato, Roseann E. Peterson, Jue-Sheng Ong, Stuart MacGregor, Alexis C. Edwards, Toni-Kim Clarke, Josef Frank, et al. “Evidence of causal effect of major depression on alcohol dependence: findings from the psychiatric genomics consortium.Psychol Med 49, no. 7 (May 2019): 1218–26. https://doi.org/10.1017/S0033291719000667.
Polimanti R, Peterson RE, Ong J-S, MacGregor S, Edwards AC, Clarke T-K, et al. Evidence of causal effect of major depression on alcohol dependence: findings from the psychiatric genomics consortium. Psychol Med. 2019 May;49(7):1218–26.
Polimanti, Renato, et al. “Evidence of causal effect of major depression on alcohol dependence: findings from the psychiatric genomics consortium.Psychol Med, vol. 49, no. 7, May 2019, pp. 1218–26. Pubmed, doi:10.1017/S0033291719000667.
Polimanti R, Peterson RE, Ong J-S, MacGregor S, Edwards AC, Clarke T-K, Frank J, Gerring Z, Gillespie NA, Lind PA, Maes HH, Martin NG, Mbarek H, Medland SE, Streit F, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Agrawal A, Edenberg HJ, Kendler KS, Lewis CM, Sullivan PF, Wray NR, Gelernter J, Derks EM. Evidence of causal effect of major depression on alcohol dependence: findings from the psychiatric genomics consortium. Psychol Med. 2019 May;49(7):1218–1226.
Journal cover image

Published In

Psychol Med

DOI

EISSN

1469-8978

Publication Date

May 2019

Volume

49

Issue

7

Start / End Page

1218 / 1226

Location

England

Related Subject Headings

  • United Kingdom
  • Psychiatry
  • Middle Aged
  • Mendelian Randomization Analysis
  • Male
  • Linkage Disequilibrium
  • Humans
  • Genomics
  • Genome-Wide Association Study
  • Genetic Association Studies