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Papers of the Week


Papers: 18 Dec 2021 - 24 Dec 2021


Human Studies


2021 Dec 17


Pain

Genome-wide association study of pain sensitivity assessed by questionnaire and the cold pressor test.

Authors

Abstract

We deployed an online pain sensitivity questionnaire (PSQ) and an at-home version of the cold pressor test (CPT) in a large genotyped cohort. We performed genome-wide association studies (GWAS) on the PSQ score (25,321 participants) and CPT duration (6,853). We identified one new genome-wide significant locus associated with the PSQ score, which was located in the TSSC1 (also known as EIPR1) gene (rs58194899, OR = 0.950 [0.933-0.967], P-value = 1.9*10-8). Although high pain sensitivity measured by both PSQ and CPT was associated with individual history of chronic and acute pains, genetic correlation analyses surprisingly suggested an opposite direction: PSQ score was inversely genetically correlated neck and shoulder pain (rg = -0.71), rheumatoid arthritis (-0.68), and osteoarthritis (-0.38), and with known risk factors, such as the length of working week (-0.65), smoking (-0.36), or extreme BMI (-0.23). Gene-based analysis followed by pathway analysis showed that GWAS results were enriched for genes expressed in the brain and involved in neuronal development and glutamatergic synapse signaling pathways. Finally, we confirmed that females with red hair were more sensitive to pain and found that genetic variation in the MC1R gene was associated with an increase in self-perceived pain sensitivity as assessed by the PSQ.