英国生物银行肌肉骨骼疼痛药理学结果的全基因组关联研究。

IF 2.9 3区 医学 Q2 GENETICS & HEREDITY
Song Li, Geert Poelmans, Regina L. M. van Boekel, Marieke J. H. Coenen
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引用次数: 0

摘要

肌肉骨骼疼痛的药理学治疗从非甾体抗炎药开始,然后是弱或强阿片类药物,直到疼痛得到控制。然而,由于个体间的差异,治疗效果往往不尽如人意。为了研究治疗结果差异的遗传成分,我们对来自英国生物银行的约23,000名肌肉骨骼疼痛患者进行了全基因组关联研究(GWAS)。比较非甾体抗炎药与阿片类药物使用者作为非甾体抗炎药治疗结果的反映。我们在4号染色体上发现了一个全基因组显著的hit (rs549224715, P = 3.88 × 10-8)。具有提示意义的(P -6)基因座在功能上被注释到18个靶基因,包括4个与神经性疼痛过程或肌肉骨骼发育相关的基因。途径和网络分析确定了免疫相关过程和(假定的)EGFR的核心作用。然而,这项研究应被视为阐明肌肉骨骼疼痛治疗的遗传背景的第一步。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Genome-wide association study on pharmacological outcomes of musculoskeletal pain in UK Biobank

Genome-wide association study on pharmacological outcomes of musculoskeletal pain in UK Biobank

Genome-wide association study on pharmacological outcomes of musculoskeletal pain in UK Biobank
The pharmacological management of musculoskeletal pain starts with NSAIDs, followed by weak or strong opioids until the pain is under control. However, the treatment outcome is usually unsatisfying due to inter-individual differences. To investigate the genetic component of treatment outcome differences, we performed a genome-wide association study (GWAS) in ~23,000 participants with musculoskeletal pain from the UK Biobank. NSAID vs. opioid users were compared as a reflection of the treatment outcome of NSAIDs. We identified one genome-wide significant hit in chromosome 4 (rs549224715, P = 3.88 × 10−8). Suggestive significant (P < 1 × 10−6) loci were functionally annotated to 18 target genes, including four genes linked to neuropathic pain processes or musculoskeletal development. Pathway and network analyses identified immunity-related processes and a (putative) central role of EGFR. However, this study should be viewed as a first step to elucidate the genetic background of musculoskeletal pain treatment.
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来源期刊
Pharmacogenomics Journal
Pharmacogenomics Journal 医学-药学
CiteScore
7.20
自引率
0.00%
发文量
35
审稿时长
6-12 weeks
期刊介绍: The Pharmacogenomics Journal is a print and electronic journal, which is dedicated to the rapid publication of original research on pharmacogenomics and its clinical applications. Key areas of coverage include: Personalized medicine Effects of genetic variability on drug toxicity and efficacy Identification and functional characterization of polymorphisms relevant to drug action Pharmacodynamic and pharmacokinetic variations and drug efficacy Integration of new developments in the genome project and proteomics into clinical medicine, pharmacology, and therapeutics Clinical applications of genomic science Identification of novel genomic targets for drug development Potential benefits of pharmacogenomics.
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