慢性疼痛
止痛药
全基因组关联研究
遗传力
遗传建筑学
医学
类阿片
精神科
遗传学
生物
基因
表型
内科学
单核苷酸多态性
基因型
受体
作者
Sylvanus Toikumo,Rachel Vickers‐Smith,Zeal Jinwala,Heng Xu,Divya Saini,Emily E. Hartwell,Mirko Pavicic,Kyle A. Sullivan,Ke Xu,Daniel Jacobson,Joel Gelernter,Christopher T. Rentsch,Mirko Pavicic,Eli A. Stahl,Martin D. Cheatle,Hang Zhou,Stephen G. Waxman,Amy C. Justice,Rachel L. Kember,Henry R. Kranzler
出处
期刊:Nature Medicine
[Springer Nature]
日期:2024-03-01
卷期号:30 (4): 1075-1084
被引量:5
标识
DOI:10.1038/s41591-024-02839-5
摘要
Chronic pain is a common problem, with more than one-fifth of adult Americans reporting pain daily or on most days. It adversely affects the quality of life and imposes substantial personal and economic costs. Efforts to treat chronic pain using opioids had a central role in precipitating the opioid crisis. Despite an estimated heritability of 25-50%, the genetic architecture of chronic pain is not well-characterized, in part because studies have largely been limited to samples of European ancestry. To help address this knowledge gap, we conducted a cross-ancestry meta-analysis of pain intensity in 598,339 participants in the Million Veteran Program, which identified 126 independent genetic loci, 69 of which are new. Pain intensity was genetically correlated with other pain phenotypes, level of substance use and substance use disorders, other psychiatric traits, education level and cognitive traits. Integration of the genome-wide association studies findings with functional genomics data shows enrichment for putatively causal genes (n = 142) and proteins (n = 14) expressed in brain tissues, specifically in GABAergic neurons. Drug repurposing analysis identified anticonvulsants, β-blockers and calcium-channel blockers, among other drug groups, as having potential analgesic effects. Our results provide insights into key molecular contributors to the experience of pain and highlight attractive drug targets.
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