Pan Qi, Cai Tengda, Tao Yiwen, Yang Luning, Compte Roger, Naeini Maryam Kazemi, Haque Mainul, Dottorini Tania, Williams Frances Mk, Meng Weihua
Nottingham Ningbo China Beacons of Excellence Research and Innovation Institute, University of Nottingham Ningbo China, Ningbo, Zhejiang, China.
Department Twin Research and Genetic Epidemiology, School of Life Course Science, King's College London, London, England, UK.
Mol Pain. 2025 Jan-Dec;21:17448069251346603. doi: 10.1177/17448069251346603. Epub 2025 Jun 12.
Widespread pain is a hallmark characteristic of fibromyalgia, commonly affecting older individuals. This study aimed to identify novel genetic variants associated with widespread pain by utilizing the extensive UK Biobank dataset.
We conducted a primary genome-wide association study (GWAS) using a novel definition of widespread pain, defined as pain experienced all over the body during the past month. Sex-stratified GWAS analysis approach was also performed to analyze the impact of sex on widespread pain.
The primary GWAS identified one novel significant genetic locus (rs34691025, = 1.76 × 10) on chromosome 5q13.2 within the gene and several loci that approached genome-wide significance. The sex-stratified GWAS outputs revealed biological difference widespread pain between males and females, with a novel locus identified in the female-specific analysis within the gene on chromosome 10. Genetic Correlation analysis demonstrated significant genetic correlations between widespread pain and other phenotypes, including joint disorders and spondylosis. The PheWAS revealed associations between the significant genetic variants with hearing disorders and cardiovascular diseases. A two-sample Mendelian randomization analysis found no significant causal association between hearing loss and widespread pain.
Our study advances the understanding of the genetic factors contributing to widespread pain, highlighting notable differences between males and females and identifying a novel genetic locus associated with this condition.
广泛性疼痛是纤维肌痛的一个标志性特征，常见于老年人。本研究旨在利用庞大的英国生物银行数据集，识别与广泛性疼痛相关的新基因变异。
我们使用一种新的广泛性疼痛定义进行了一项全基因组关联研究（GWAS），该定义为过去一个月内全身各处都经历的疼痛。还采用了按性别分层的GWAS分析方法来分析性别对广泛性疼痛的影响。
主要的GWAS在5号染色体q13.2区域的 基因内确定了一个新的显著基因位点（rs34691025， = 1.76 × 10）以及几个接近全基因组显著性的位点。按性别分层的GWAS结果揭示了男性和女性在广泛性疼痛方面的生物学差异，在10号染色体上 基因的女性特异性分析中确定了一个新位点。遗传相关性分析表明广泛性疼痛与其他表型之间存在显著的遗传相关性，包括关节疾病和脊椎病。表型组关联研究（PheWAS）揭示了显著基因变异与听力障碍和心血管疾病之间的关联。两样本孟德尔随机化分析未发现听力损失与广泛性疼痛之间存在显著的因果关联。
我们的研究增进了对导致广泛性疼痛的遗传因素的理解，突出了男性和女性之间的显著差异，并确定了一个与这种情况相关的新基因位点。
