Chronic pain (CP) affects 30% – 50% of the population and is one of the leading causes of disability worldwide. Despite its burden on public health, research into the underlying genetics of CP is limited. Here, we present one of the largest genome-wide association study (GWAS) so far conducted on CP using data from UK Biobank (controls N=69,627; cases N=188,352). CP was modelled as a binary trait and assessed by participants’ survey responses to pain occurring in any body region for ≥ 3 months. Two genome-wide significant associated loci (P<5x10-8) were identified which mapped to genes ADAMTS6 and LEMD2. A gene-based analyses further identified genes in the 17q21.31 locus (DCAKD and NMT1) associated with CP. Gene-enrichment analysis including tissue- and pathway- based analyses failed to detect meaningful associations.
Genetic correlations revealed significant (P < 3.81x10-5) relationships with 324 traits, including depression and BMI. These results were then followed up by estimating the Genetic Causality Proportion which identified 63 significant (P < 3.66x10-5) phenotypes associated with CP. These include a variety of mental, disease, diet, pain and other environmental phenotypes. Furthermore, a bidirectional Generalized Summary-data-based Mendelian Randomization revealed 19 potential causal associations, including educational attainment and smoking.
In conclusion, we identified two novel genome-wide significant associations, ADAMTS6 and LEMD2. A gene-based test (P<2.06x10-6) also revealed genes in the 17q21.31 locus (DCAKD and NMT1) associated with CP.