Chronic pain (CP) is a leading cause of disability worldwide with complex aetiologies that remain elusive. Here we addressed this issue by performing a GWAS on a large UK Biobank sample (N=188,352 cases & N=69,627 controls) which identified two independent loci associated with CP near ADAMTS6 and LEMD2. Gene-based tests revealed additional CP-associated genes (DCAKD, NMT1, MLN, IP6K3). Across 1328 complex traits, 548 (41%) were genetically correlated with CP, of which 175 (13%) showed genetic causal relationships using the latent causal variable approach and Mendelian randomization. In particular, major depressive disorder, anxiety, smoking, body fat & BMI were found to increase the risk of CP, whereas diet, walking for pleasure & higher educational attainment were associated with a reduced risk (i.e., protective effect). This data-driven hypothesis-free approach has uncovered several specific risk factors that warrant further examination in longitudinal trials to help deliver effective early screening & management strategies for CP.

中文翻译：

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GWAS揭示了慢性疼痛的遗传，生活方式和环境危险因素

慢性疼痛（CP）是世界范围内致残的主要原因，其复杂的病因仍然难以捉摸。在这里，我们通过对大型英国生物库样本（N = 188,352例和N = 69,627例对照）进行GWAS解决了这个问题，该样本确定了ADAMTS6和LEMD2附近与CP相关的两个独立基因座。基于基因的测试揭示了其他与CP相关的基因（DCAKD，NMT1，MLN，IP6K3）。在1328个复杂性状中，有548个（41％）与CP遗传相关，其中175个（13％）使用潜在因果变量方法和孟德尔随机化显示了遗传因果关系。特别是，发现严重的抑郁症，焦虑症，吸烟，体脂和BMI会增加CP的风险，而饮食，散步，享乐和较高的教育水平则可以降低CP的风险（即，保护作用）。