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

Multi-trait genome-wide association study of opioid addiction: OPRM1 and beyond.
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DOI:
10.1038/s41598-022-21003-y
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发表时间:
2022-10-07
期刊:
影响因子:
4.6
通讯作者:
--
中科院分区:
综合性期刊3区
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--
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阿片类药物成瘾(OA)是中度遗传的,但只有rs 1799971,OPRM 1中的A118 G变体,已被确定为与OA的全基因组显著相关,并独立复制。我们应用基因组结构方程模型对新的阿片类药物成瘾遗传学联盟(GENOA)数据以及已发表的研究(精神病学基因组学联盟,百万退伍军人计划和合作伙伴健康)进行了GWAS,包括23,367例病例和88,114名欧洲血统个体的有效样本量。各种OA表型之间的遗传相关性一致较高(rg > 0.9)。我们观察到迄今为止最强有力的证据OPRM 1:前导SNP rs 9478500(p = 2.56 × 10-9)。基于基因的分析确定了与PPP 6C和FURIN的新的全基因组显著关联。这些基因座内的变异体似乎对成瘾和相关性状具有多效性。
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.
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