Department of Twin Research and Genetic Epidemiology, School of Life Course Sciences, King's College London, London, United Kingdom.
Laboratory of Theoretical and Applied Functional Genomics, Faculty of Natural Sciences, Novosibirsk State University, Novosibirsk, Russia.
Pain. 2019 Jun;160(6):1361-1373. doi: 10.1097/j.pain.0000000000001514.
Back pain (BP) is a common condition of major social importance and poorly understood pathogenesis. Combining data from the UK Biobank and CHARGE consortium cohorts allowed us to perform a very large genome-wide association study (total N = 509,070) and examine the genetic correlation and pleiotropy between BP and its clinical and psychosocial risk factors. We identified and replicated 3 BP-associated loci, including one novel region implicating SPOCK2/CHST3 genes. We provide evidence for pleiotropic effects of genetic factors underlying BP, height, and intervertebral disk problems. We also identified independent genetic correlations between BP and depression symptoms, neuroticism, sleep disturbance, overweight, and smoking. A significant enrichment for genes involved in the central nervous system and skeletal tissue development was observed. The study of pleiotropy and genetic correlations, supported by the pathway analysis, suggests at least 2 strong molecular axes of BP genesis, one related to structural/anatomical factors such as intervertebral disk problems and anthropometrics, and another related to the psychological component of pain perception and pain processing. These findings corroborate with the current biopsychosocial model as a paradigm for BP. Overall, the results demonstrate BP to have an extremely complex genetic architecture that overlaps with the genetic predisposition to its biopsychosocial risk factors. The work sheds light on pathways of relevance in the prevention and management of low BP.
背痛（BP）是一种具有重要社会意义且发病机制尚不清楚的常见疾病。我们结合了英国生物银行和 CHARGE 联盟队列的数据，进行了一项非常大规模的全基因组关联研究（总 N = 509,070），并研究了 BP 与其临床和社会心理风险因素之间的遗传相关性和多效性。我们确定并复制了 3 个与 BP 相关的基因座，包括一个新的涉及 SPOCK2/CHST3 基因的区域。我们提供了证据表明，BP、身高和椎间盘问题的遗传因素存在多效性效应。我们还发现了 BP 与抑郁症状、神经质、睡眠障碍、超重和吸烟之间的独立遗传相关性。观察到与中枢神经系统和骨骼组织发育相关的基因存在显著富集。多效性和遗传相关性的研究，以及通路分析的支持，表明至少有 2 个与 BP 发生相关的强烈分子轴，一个与椎间盘问题和人体测量等结构/解剖因素有关，另一个与疼痛感知和疼痛处理的心理成分有关。这些发现与当前的生物心理社会模型作为 BP 的范例相符。总的来说，这些结果表明 BP 具有极其复杂的遗传结构，与 BP 的生物心理社会风险因素的遗传易感性重叠。这项工作为低 BP 的预防和管理提供了有意义的途径。
