Genomics of pain in osteoarthritis

J.M. Dawes,S.B. McMahon,M. Thakur

doi:10.1016/j.joca.2013.06.010

Abstract

SummaryOsteoarthritis (OA) accounts for the majority of the disease burden for musculoskeletal disorders and is one of the leading causes of disability worldwide. This disability is the result not of the cartilage loss that defines OA radiographically, but of the chronic pain whose presence defines symptomatic OA. It is becoming clear that many genes, each with a small effect size, contribute to the risk of developing OA. However, the genetics of OA pain are only just starting to be explored. This review will describe the first genes to have been identified in genomic studies of OA pain, as well as the possible dual roles of genes previously identified in genomic studies of OA in the context of pain. Difficulties associated with attempting to characterise the genetics of OA pain will be discussed and promising future avenues of research into genetic and epigenetic factors affecting OA pain described.

Highlights

Recent years have seen substantial advances in the understanding of the genetic architecture of osteoarthritis (OA)
Unbiased genetic screens of large OA cohorts such as those included in the arcOGEN and TREAT-OA consortia have had sufficient power to reveal a wide range of relatively common susceptibility loci[1]
This study showed that single nucleotide polymorphism (SNP) in P2X7 associated with pain intensity in a post-masectomy pain cohort

Summary

Genomics of pain in osteoarthritis

Osteoarthritis (OA) accounts for the majority of the disease burden for musculoskeletal disorders and is one of the leading causes of disability worldwide. This disability is the result not of the cartilage loss that defines OA radiographically, but of the chronic pain whose presence defines symptomatic OA. This review will describe the first genes to have been identified in genomic studies of OA pain, as well as the possible dual roles of genes previously identified in genomic studies of OA in the context of pain. Difficulties associated with attempting to characterise the genetics of OA pain will be discussed and promising future avenues of research into genetic and epigenetic factors affecting OA pain described

Introduction

Which genes are currently known to associate with OA pain?

Effect in OA

Hypofunctional SNPs associate with less severe pain

Genes identified in expression studies

Table II

Role in pain

Tenascin C

Down regulated

The limitations of genomic studies of painful joint disorders

Endophenotypes in symptomatic OA

Conclusion