Author:
Gaddis Nathan,Mathur Ravi,Marks Jesse,Zhou Linran,Quach Bryan,Waldrop Alex,Levran Orna,Agrawal Arpana,Randesi Matthew,Adelson Miriam,Jeffries Paul W.,Martin Nicholas G.,Degenhardt Louisa,Montgomery Grant W.,Wetherill Leah,Lai Dongbing,Bucholz Kathleen,Foroud Tatiana,Porjesz Bernice,Runarsdottir Valgerdur,Tyrfingsson Thorarinn,Einarsson Gudmundur,Gudbjartsson Daniel F.,Webb Bradley Todd,Crist Richard C.,Kranzler Henry R.,Sherva Richard,Zhou Hang,Hulse Gary,Wildenauer Dieter,Kelty Erin,Attia John,Holliday Elizabeth G.,McEvoy Mark,Scott Rodney J.,Schwab Sibylle G.,Maher Brion S.,Gruza Richard,Kreek Mary Jeanne,Nelson Elliot C.,Thorgeirsson Thorgeir,Stefansson Kari,Berrettini Wade H.,Gelernter Joel,Edenberg Howard J.,Bierut Laura,Hancock Dana B.,Johnson Eric Otto
Abstract
AbstractOpioid addiction (OA) is moderately heritable, yet only rs1799971, the A118G variant in OPRM1, has been identified as a genome-wide significant association with OA and independently replicated. We applied genomic structural equation modeling to conduct a GWAS of the new Genetics of Opioid Addiction Consortium (GENOA) data together with published studies (Psychiatric Genomics Consortium, Million Veteran Program, and Partners Health), comprising 23,367 cases and effective sample size of 88,114 individuals of European ancestry. Genetic correlations among the various OA phenotypes were uniformly high (rg > 0.9). We observed the strongest evidence to date for OPRM1: lead SNP rs9478500 (p = 2.56 × 10–9). Gene-based analyses identified novel genome-wide significant associations with PPP6C and FURIN. Variants within these loci appear to be pleiotropic for addiction and related traits.
Funder
National Institute on Drug Abuse
Dr. Miriam and Sheldon G. Adelson Medical Research Foundation
National Institute on Alcohol Abuse and Alcoholism
European Commission to the painFACT project
Pennsylvania State Department of Health Tobacco Settlement
National Center for Advancing Translational Sciences
Publisher
Springer Science and Business Media LLC
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