Multi-trait genome-wide association study of opioid addiction: OPRM1 and beyond

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dc.contributor.authorGaddis, Nathan
dc.contributor.authorMathur, Ravi
dc.contributor.authorMarks, Jesse
dc.contributor.authorZhou, Linran
dc.contributor.authorQuach, Bryan
dc.contributor.authorWaldrop, Alex
dc.contributor.authorLevran, Orna
dc.contributor.authorAgrawal, Arpana
dc.contributor.authorRandesi, Matthew
dc.contributor.authorAdelson, Miriam
dc.contributor.authorJeffries, Paul W.
dc.contributor.authorMartin, Nicholas G.
dc.contributor.authorDegenhardt, Louisa
dc.contributor.authorMontgomery, Grant W.
dc.contributor.authorWetherill, Leah
dc.contributor.authorLai, Dongbing
dc.contributor.authorBucholz, Kathleen
dc.contributor.authorForoud, Tatiana
dc.contributor.authorPorjesz, Bernice
dc.contributor.authorRunarsdottir, Valgerdur
dc.contributor.authorTyrfingsson, Thorarinn
dc.contributor.authorEinarsson, Gudmundur
dc.contributor.authorGudbjartsson, Daniel F.
dc.contributor.authorWebb, Bradley Todd
dc.contributor.authorCrist, Richard C.
dc.contributor.authorKranzler, Henry R.
dc.contributor.authorSherva, Richard
dc.contributor.authorZhou, Hang
dc.contributor.authorHulse, Gary
dc.contributor.authorWildenauer, Dieter
dc.contributor.authorKelty, Erin
dc.contributor.authorAttia, John
dc.contributor.authorHolliday, Elizabeth G.
dc.contributor.authorMcEvoy, Mark
dc.contributor.authorScott, Rodney J.
dc.contributor.authorSchwab, Sibylle G.
dc.contributor.authorMaher, Brion S.
dc.contributor.authorGruza, Richard
dc.contributor.authorKreek, Mary Jeanne
dc.contributor.authorNelson, Elliot C.
dc.contributor.authorThorgeirsson, Thorgeir
dc.contributor.authorStefansson, Kari
dc.contributor.authorBerrettini, Wade H.
dc.contributor.authorGelernter, Joel
dc.contributor.authorEdenberg, Howard J.
dc.contributor.authorBierut, Laura
dc.contributor.authorHancock, Dana B.
dc.contributor.authorJohnson, Eric Otto
dc.contributor.departmentMedical and Molecular Genetics, School of Medicine
dc.date.accessioned2023-09-18T14:51:59Z
dc.date.available2023-09-18T14:51:59Z
dc.date.issued2022-10-07
dc.description.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.
dc.eprint.versionFinal published version
dc.identifier.citationGaddis N, Mathur R, Marks J, et al. Multi-trait genome-wide association study of opioid addiction: OPRM1 and beyond. Sci Rep. 2022;12(1):16873. Published 2022 Oct 7. doi:10.1038/s41598-022-21003-y
dc.identifier.urihttps://hdl.handle.net/1805/35596
dc.language.isoen_US
dc.publisherSpringer Nature
dc.relation.isversionof10.1038/s41598-022-21003-y
dc.relation.journalScientific Reports
dc.rightsAttribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourcePMC
dc.subjectGenetic association study
dc.subjectHaplotypes
dc.subjectOpioid-related disorders
dc.subjectFurin
dc.titleMulti-trait genome-wide association study of opioid addiction: OPRM1 and beyond
dc.typeArticle
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