Extended report providing a robust phenotype, and were compared to a pain- free control group to avoid erroneous associations due to the presence of non-persistent CWP, WP or regional pain disorders which may also be inﬂuenced by genetic variation in the HPA axis. However, this results in a limited sample size. A novel method was used to quantify pain by creating a composite score of the number of body regions, from 0 to 29, making it possible to examine the relationship between genetic variation and mus- culoskeletal pain in the entire study population thus increasing statistical power. One limitation of the study is that ethnicity of participants was not determined; however, participants were derived from predominantly white Caucasian geographic areas. Another limi- tation of our study is that due to limited power we have chosen not to correct for multiple testing. Indeed correcting for the num- ber of effective tests, accounting for LD between SNPs, using the methodology proposed by Li and Ji35 would result in a p value cut-off of 0.00037; none of the associations observed reached this level of signiﬁcance. However, this method of correction is comparatively stringent and may result in false negatives if applied. To be certain whether these are true pain susceptibility loci or false positives, independent replication of these ﬁndings in larger cohorts is essential. It was anticipated that similar ﬁndings would be detected with the two pain outcomes as the patients with CWP also tend to have a high number of pain sites. There is some consistency between the ﬁndings of the CWP and maximum number of pain sites analysis but also some discrepancies. This may be explained by the reduced power in the CWP analysis or because the max- imum pain score is capturing acute and chronic pain which may not be inﬂuenced by the same genetic factors. In conclusion, we report the ﬁrst evidence that genetic vari- ation in the primary stress response system inﬂuences suscep- tibility to musculoskeletal pain in a general population sample. However, the associations reported are modest, sometimes explained by psychological comorbidity and require replication in a large independent cohort to determine whether they play a role in the aetiology of musculoskeletal pain. Acknowledgements The authors would like to thank the participants and staff at the three general practices who contributed to the EPIFUND study. They also thank the administrative and laboratory staff at the arc Epidemiology Unit for their contributions to the project. Funding The study was funded by a grant from the Arthritis Research Campaign, grant Ref: 17552. Competing interests None. Ethics approval This study was conducted with the approval of the local research ethics committee and the University of Manchester. 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