| Title: | Evidence of causal effect of major depression on alcohol dependence: findings from the psychiatric genomics consortium |
| Journal: | Psychological Medicine |
| Published: | 1 Apr 2019 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/30929657/ |
| DOI: | https://doi.org/10.1017/s0033291719000667 |
| URL: | https://europepmc.org/articles/pmc6565601?pdf=render |
Publication 13766
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Abstract
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.</p>
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).</p>
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.</p>
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.</p>
17 Keywords
- Adult
- Aged
- Alcoholism
- Causality
- Cohort Studies
- Comorbidity
- Depressive Disorder, Major
- Female
- Genetic Association Studies
- Genome-Wide Association Study
- Genomics
- Humans
- Linkage Disequilibrium
- Male
- Mendelian Randomization Analysis
- Middle Aged
- United Kingdom
23 Authors
- Renato Polimanti
- Roseann E. Peterson
- Jue-Sheng Ong
- Stuart MacGregor
- Alexis C. Edwards
- Toni-Kim Clarke
- Josef Frank
- Zachary Gerring
- Nathan A. Gillespie
- Penelope A. Lind
- Hermine H. Maes
- Nicholas G. Martin
- Hamdi Mbarek
- Sarah E. Medland
- Fabian Streit
- Arpana Agrawal
- Howard J. Edenberg
- Kenneth S. Kendler
- Cathryn M. Lewis
- Patrick F. Sullivan
- Naomi R. Wray
- Joel Gelernter
- Eske M. Derks
1 Application
| Application ID | Title |
|---|---|
| 25331 | Gene mapping and genetic correlation across complex traits |
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