Journal article
Parsing genetically influenced risk pathways: genetic loci impact problematic alcohol use via externalizing and specific risk
Translational psychiatry, Vol.12(1), 420
01/01/2022
DOI: 10.1038/s41398-022-02171-x
PMCID: PMC9525649
PMID: 36180423
Abstract
Genome-wide association studies (GWAS) identify genetic variants associated with a trait, regardless of how those variants are associated with the outcome. Characterizing whether variants for psychiatric outcomes operate via specific versus general pathways provides more informative measures of genetic risk. In the current analysis, we used multivariate GWAS to tease apart variants associated with problematic alcohol use (ALCP-total) through either a shared risk for externalizing (EXT) or a problematic alcohol use-specific risk (ALCP-specific). SNPs associated with ALCP-specific were primarily related to alcohol metabolism. Genetic correlations showed ALCP-specific was predominantly associated with alcohol use and other forms of psychopathology, but not other forms of substance use. Polygenic scores for ALCP-total were associated with multiple forms of substance use, but polygenic scores for ALCP-specific were only associated with alcohol phenotypes. Polygenic scores for both ALCP-specific and EXT show different patterns of associations with alcohol misuse across development. Our results demonstrate that focusing on both shared and specific risk can better characterize pathways of risk for substance use disorders. Parsing risk pathways will become increasingly relevant as genetic information is incorporated into clinical practice.
Details
- Title: Subtitle
- Parsing genetically influenced risk pathways: genetic loci impact problematic alcohol use via externalizing and specific risk
- Creators
- Peter B BarrTravis T MallardSandra Sanchez-RoigeHolly E PooreRichard Karlsson LinnérBernice PorjeszVictor HesselbrockTatiana ForoudArpana AgrawalDanielle DickHoward J EdenbergJohn NurrnbergerYunlong LiuSamuel KupermanJohn KramerJacquelyn MeyersChella KamarajanAshwini PandeyLaura BierutJohn RiceKathleen BucholzMarc SchuckitJay TischfieldRonald HartJessica SalvatoreLaura AlmasyAlison GoateManav KapoorPaul SlesingerDenise ScottLance BauerLeah WetherillXiaolong XueiDongbing LaiSean O’ConnorMartin PlaweckiLaura AcionGrace ChanDavid B ChorlianJian ZhangSivan KinreichGayathri PandeyMichael ChaoAndrey AnokhinVivia McCutcheonScott SacconeFazil AlievHemin ChinAbbas ParsianIrwin D WaldmanAbraham A PalmerK. Paige Harden
- Resource Type
- Journal article
- Publication Details
- Translational psychiatry, Vol.12(1), 420
- DOI
- 10.1038/s41398-022-02171-x
- PMID
- 36180423
- PMCID
- PMC9525649
- NLM abbreviation
- Transl Psychiatry
- ISSN
- 2158-3188
- eISSN
- 2158-3188
- Publisher
- Nature Publishing Group
- Grant note
- DOI: 10.13039/100000026, name: U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse, award: DP1DA054394, R01DA050721; DOI: 10.13039/100000027, name: U.S. Department of Health & Human Services | NIH | National Institute on Alcohol Abuse and Alcoholism, award: R01AA015416, P50AA022537; name: U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse; name: U.S. Department of Health & Human Services | NIH | National Institute on Alcohol Abuse and Alcoholism
- Language
- English
- Date published
- 01/01/2022
- Academic Unit
- Psychiatry
- Record Identifier
- 9984297512602771
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