Genome-wide association study identifies novel genetic variants associated with widespread pain in the UK Biobank (N = 172,230).

IF 2.8 3区医学 Q2 NEUROSCIENCES

Molecular Pain Pub Date : 2025-01-01 Epub Date: 2025-06-12 DOI:10.1177/17448069251346603

Qi Pan, Tengda Cai, Yiwen Tao, Luning Yang, Roger Compte, Maryam Kazemi Naeini, Mainul Haque, Tania Dottorini, Frances Mk Williams, Weihua Meng

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引用次数: 0

Abstract

Objectives: 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.

Methods: 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.

Results: The primary GWAS identified one novel significant genetic locus (rs34691025, p = 1.76 × 10^-8) on chromosome 5q13.2 within the ARHGEF28 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 LRMDA 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.

Conclusions: 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.

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全基因组关联研究在英国生物银行（N = 172,230）中发现了与广泛性疼痛相关的新型遗传变异。

目的：广泛的疼痛是纤维肌痛的一个显著特征，通常影响老年人。本研究旨在通过利用广泛的英国生物银行数据集，确定与广泛性疼痛相关的新型遗传变异。方法：我们进行了一项全基因组关联研究（GWAS），使用了广泛性疼痛的新定义，定义为过去一个月内全身疼痛。还采用性别分层GWAS分析方法分析性别对广泛性疼痛的影响。结果：初级GWAS在ARHGEF28基因的5q13.2染色体上发现了1个新的显著遗传位点（rs34691025, p = 1.76 × 10-8）和几个接近全基因组意义的位点。性别分层的GWAS结果揭示了男性和女性之间普遍存在的疼痛的生物学差异，在10号染色体上的LRMDA基因的女性特异性分析中发现了一个新的位点。遗传相关分析表明，广泛疼痛和其他表型（包括关节疾病和颈椎病）之间存在显著的遗传相关性。PheWAS揭示了听力障碍和心血管疾病的显著遗传变异之间的联系。一项双样本孟德尔随机分析发现，听力损失和广泛性疼痛之间没有明显的因果关系。结论：我们的研究提高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着差异，并确定了与这种情况相关的新的遗传位点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular Pain 医学-神经科学

CiteScore

5.60

自引率

3.00%

发文量

审稿时长

6-12 weeks

期刊介绍： Molecular Pain is a peer-reviewed, open access journal that considers manuscripts in pain research at the cellular, subcellular and molecular levels. Molecular Pain provides a forum for molecular pain scientists to communicate their research findings in a targeted manner to others in this important and growing field.