Genome-wide association study of knee pain identifies associations with GDF5 and COL27A1 in UK Biobank

Meng Wang ,Mark J Adams,Colin N.a Palmer ,Michelle S Yau,Adam Auton,Kathleen A Ryan,Braxton D Mitchell,Rebecca D Jackson,Jingchunzi Shi,Joanne M Jordan,Andrew M Mcintosh,Blair H Smith

doi:10.1038/s42003-019-0568-2

Abstract

Knee pain is one of the most common musculoskeletal complaints that brings people to medical attention. Approximately 50% of individuals over the age of 50 report an experience of knee pain within the past 12 months. We sought to identify the genetic variants associated with knee pain in 171,516 subjects from the UK Biobank cohort and seek supporting evidence in cohorts from 23andMe, the Osteoarthritis Initiative, and the Johnston County Osteoarthritis Project. We identified two loci that reached genome-wide significance in the UK Biobank: rs143384, located in GDF5 (P = 1.32 × 10−12), a gene previously implicated in osteoarthritis; and rs2808772, located near COL27A1 (P = 1.49 × 10−8). These findings were supported in cohorts with self-reported osteoarthritis/radiographic knee osteoarthritis without pain information. In this report on genome-wide association of knee pain, we identified two loci in or near GDF5 and COL27A1 that are associated with knee pain.

Highlights

Knee pain is one of the most common musculoskeletal complaints that brings people to medical attention
After removing samples from non-British participants, those who were related with another individual in the cohort and those who failed quality control (QC), we identified 22,204 cases (12,062 males and 10,142 females) and 149,312 controls (71,480 males and 77,832 females) for the Genome-wide association studies (GWAS) association analysis and there were 15,377,520 single nucleotide polymorphism (SNPs) available for the GWAS analysis
In the first reported GWAS of knee pain using the UK Biobank resource, we identified variants in or near GDF5 and COL27A1, which were subsequently supported in osteoarthritis cohorts from the 23andMe, OAI and JoCo cohorts

Summary

Introduction

Knee pain is one of the most common musculoskeletal complaints that brings people to medical attention. We identified two loci that reached genome-wide significance in the UK Biobank: rs143384, located in GDF5 (P = 1.32 × 10−12), a gene previously implicated in osteoarthritis; and rs2808772, located near COL27A1 (P = 1.49 × 10−8). These findings were supported in cohorts with self-reported osteoarthritis/radiographic knee osteoarthritis without pain information. Knee pain describes a specific area of pain inside the knee or diffuse pain around knee area[1] It is one of the most common musculoskeletal complaints that bring people to medical attention[2]. Similar risk factors are reported in studies of knee osteoarthritis which included kneeling and squatting as further risk factors[12,13]

Methods

Results

Conclusion