A Genome-Wide Association Study on Widespread Pain using the UK Biobank Cohort

Student thesis: Master's ThesisMaster of Science

Abstract

Background: Pain affecting multiple sites on the body is one of the main symptoms of fibromyalgia (FM) and it can be a complementary phenotype to other sitespecific pains. The aim of this study was to explore the genetic variants associated with widespread pain in a cohort of UK Biobank participants who had completed a pain phenotyping questionnaire.

Method: Cases and controls were determined by a question answered by UK Biobank participants. The question contained 10 selections to identify different pain sites around the body. Those selecting ‘pain all over the body’ (9,551) formed the case group, and those selecting ‘none of the above’ (232,467) formed the control group. Cases were removed based on ancestry information, ethnicity, and other possible confounders. 5,670 cases and 149,312 controls met inclusion criteria. A genome-wide association study (GWAS) on pain all over the body was performed adjusting with age, sex and body mass index (BMI). The GWAS summary statistics were then annotated by the online annotation software FUMA.

Results: Based on the significance level of p < 0.05×10-8, nine GWAS-tagged candidate SNPs were found. These SNPs were located in 3 loci. In the first locus, the SNP rs17387024 found at the FAF1 gene in chromosome 1 was most significant with a p-value of 3.72×10-8. In the second locus, the most significant SNP was rs550883786 at the intergenic region in chromosome 4 with a p-value of 3.65×10-8. In the third locus, located at LINC01078 in chromosome 13, the most significant SNP was rs148500993, with a p-value of 3.65×10-8. According to related biochemical researches, FAF1 gene encodes FAF1 (FAS-associated factor 1) which plays an important role in apoptotic mechanisms by extrinsic and intrinsic pathways, and furthermore FAF1 can intervene the sensing of pain indirectly.

Conclusions: The results suggest that pain all over the body is related to altered brain function, and the steps to realise the mechanisms of this relationship lie with further characterisation of the three genomic loci identified as well as medical imaging results.
Date of Award2021
Original languageEnglish
SupervisorWeihua Meng (Supervisor), Lesley Colvin (Supervisor) & Jennifer Watson (Supervisor)

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