Malkin Ida, Williams Frances M K, LaChance Genevieve, Spector Timothy, MacGregor Alex J, Livshits Gregory
Department of Anatomy and Anthropology, Sackler Faculty of Medicine, Tel Aviv University, Israel.
Ann Hum Genet. 2014 Sep;78(5):357-66. doi: 10.1111/ahg.12074. Epub 2014 Jun 24.
Low back (LBP) and chronic widespread musculoskeletal pain (CWP) both have a significant genetic component and are associated with increased body mass index (BMI). We examined whether LBP and CWP share common genetic factors, and to what extent this correlation is modified by the genetic factors influencing BMI. Genetic analysis of binary traits such as pain is not simple, particularly if their risk is associated with age or other quantitative traits. Implementing Falconer's polygenic threshold concept for dichotomous traits inheritance, we developed new software to examine the extent of the genetic influence on LBP and CWP under age and BMI dependence. The analysis was conducted on 3266 and 2256 UK female twins, assessed for LBP and CWP, respectively. Analysis of the liability scores with threshold to LBP and CWP established substantial contribution of genetic factors to their variation (h(2) > 0.60, p<0.004-0.0003) and covariation (p=3.1E-08). Some 39% of the CWP and 70% of the LBP heritability estimates were attributable to genetic effects shared by both phenotypes, and 40% and 67% of the residual variation is caused by environmental factors simultaneously affecting both pain syndromes. However, contribution of BMI to variation/covariation of both pain phenotypes-although statistically highly significant (p∼10-7)-was not determinative.
下背部疼痛(LBP)和慢性广泛性肌肉骨骼疼痛(CWP)都有显著的遗传成分,且与体重指数(BMI)升高相关。我们研究了LBP和CWP是否共享共同的遗传因素,以及这种相关性在多大程度上受到影响BMI的遗传因素的修饰。对疼痛等二元性状进行遗传分析并不简单,尤其是当其风险与年龄或其他数量性状相关时。我们运用Falconer的多基因阈值概念来分析二分性状的遗传,开发了新软件以研究在年龄和BMI依赖性条件下遗传因素对LBP和CWP的影响程度。该分析分别在3266名和2256名接受LBP和CWP评估的英国女性双胞胎中进行。对LBP和CWP的阈值责任评分分析表明,遗传因素对其变异有显著贡献(h(2) > 0.60,p<0.004 - 0.0003)以及协变(p = 3.1E - 08)。约39%的CWP遗传力估计值和70%的LBP遗传力估计值可归因于两种表型共有的遗传效应,剩余变异的40%和67%是由同时影响两种疼痛综合征的环境因素引起的。然而,BMI对两种疼痛表型变异/协变的贡献——尽管在统计学上高度显著(p ∼ 10 - 7)——并非决定性因素。