GenOmics, Bioinformatics, and Translational Research Center, Biostatistics and Epidemiology Division, RTI International, Research Triangle Park, NC, USA.
The Laboratory of the Biology of Addictive Diseases, The Rockefeller University, New York, NY, USA.
Sci Rep. 2022 Oct 7;12(1):16873. doi: 10.1038/s41598-022-21003-y.
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 (r > 0.9). We observed the strongest evidence to date for OPRM1: lead SNP rs9478500 (p = 2.56 × 10). 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.
阿片类药物成瘾（OA）具有中度遗传性，但只有 OPRM1 中的 rs1799971（A118G 变体）被确定为与 OA 具有全基因组显著关联并得到独立复制。我们应用基因组结构方程模型，对新的阿片成瘾遗传学联盟（GENOA）数据以及已发表的研究（精神遗传学联合会、百万退伍军人计划和合作伙伴健康）进行了全基因组关联研究，其中包括 23367 例病例和有效样本量为 88114 名欧洲血统个体。各种 OA 表型之间的遗传相关性普遍较高（r>0.9）。我们观察到了迄今为止与 OPRM1 最强的证据：主要 SNP rs9478500（p=2.56×10）。基于基因的分析确定了 PPP6C 和 FURIN 与成瘾和相关特征具有全基因组显著关联的新变体。这些基因座内的变体似乎对成瘾和相关特征具有多效性。
