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. 2022 Sep 1;163(9):1763-1776.
doi: 10.1097/j.pain.0000000000002568. Epub 2021 Dec 17.

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

Pierre Fontanillas  1 , Achim Kless  2 , John Bothmer  2 , Joyce Y Tung  1 ; 23andMe Research Team
Affiliations

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

Pierre Fontanillas et al. Pain. .

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 on the PSQ score (25,321 participants) and CPT duration (6853). 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 with 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 genome-wide association studies 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.

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Conflict of interest statement

The authors have no conflicts of interest to declare.

Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.

Figures

Figure 1.
Figure 1.
Manhattan plots for PSQ and CPT GWAS (panel A and B, respectively). CPT, cold pressor test; GWAS, genome-wide association studies; PSQ, pain sensitivity questionnaire.
Figure 2.
Figure 2.
Results of MC1R and hair color association with PSQ score. MC1R, melanocortin-1 receptor; PSQ, pain sensitivity questionnaire.
Figure 3.
Figure 3.
Regional association plot for TSSC1 locus and QQ plot from the PSQ GWAS. GWAS, genome-wide association studies; PSQ, pain sensitivity questionnaire.
See this image and copyright information in PMC

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