RT Journal Article SR Electronic T1 Genetic and environmental risk for chronic pain and the contribution of risk variants for psychiatric disorders. Results from Generation Scotland: Scottish Family Health Study and UK Biobank JF bioRxiv FD Cold Spring Harbor Laboratory SP 037457 DO 10.1101/037457 A1 AM McIntosh A1 LS Hall A1 Y Zeng A1 MJ Adams A1 J Gibson A1 E Wigmore A1 AM Pujils-Fernandez A1 AI Campbell A1 T-K Clarke A1 C Hayward A1 C Haley A1 DJ Porteous A1 IJ Deary A1 DJ Smith A1 BI Nicholl A1 DA Hinds A1 AV Jones A1 S Scollen A1 W Meng A1 BH Smith A1 LJ Hocking YR 2016 UL http://biorxiv.org/content/early/2016/01/21/037457.abstract AB Background Chronic pain is highly prevalent worldwide and a significant source of disability, yet its genetic and environmental risk factors are poorly understood. Its relationship with psychiatric illness, and major depressive disorder (MDD) in particular, is of particular importance. We sought to test the contribution of genetic factors and shared and unique environment to risk of chronic pain and its correlation with MDD in Generation Scotland: Scottish Family Health Study (GS:SFHS). We then sought to replicate any significant findings in the UK Biobank study.Methods Using family-based mixed-model analyses, we examined the contribution of genetics and environment to chronic pain using spouse, sibling and household groups as measures of shared environment. We then examined the correlation between chronic pain and MDD and estimated the contribution of genetic factors and shared environment. Finally, we used data from two independent genome-wide association studies to test whether chronic pain has a polygenic risk architecture and examine whether genomic risk of psychiatric disorder predicted chronic pain and whether genomic risk of chronic pain predicted MDD.Results Chronic pain is a moderately heritable trait (narrow sense heritability = 38.4%) which is more likely to be concordant in spouses and partners (variance explained 18.7%). Chronic pain is positively correlated with depression (rho = 0.13, p = 2.72x10−68) and it shows a tendency to cluster within families for genetic reasons (genetic correlation rho = 0.51, p = 8.24x10−19). Polygenic risk profiles for pain, generated using independent GWAS data, predicted chronic pain in both GS:SFHS (maximum β = 6.18x10−2, p = 4.3x10−4) and UK Biobank (maximum β = 5.68 x 10−2, p < 3x10−4). Genomic risk of MDD is also significantly associated with chronic pain in both GS:SFHS (maximum β = 6.62x10−2, p = 4.3x10−4) and UK Biobank (maximum β = 2.56x10-2, p < 3x10−4).Conclusions Genetic factors and chronic pain in a partner or spouse contribute substantially to the risk of chronic pain in the general population. Chronic pain is genetically correlated with MDD, has a polygenic architecture and is predicted by polygenic risk of MDD.