Scientific reports · 2022

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

СтатьяПоддержка исследования: вне правительства СШАПоддержка NIH: внешняя программаНазвание и аннотация: Перевод пока не подготовлен

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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

Аннотация

Opioid 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.

Предметные рубрики MeSH

Furin Genetic Predisposition to Disease Genome-Wide Association Study Humans Opioid-Related Disorders Phenotype Polymorphism, Single Nucleotide Receptors, Opioid, mu

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

Ошибки и ограничения

Аннотация

Предметные рубрики MeSH