• Maxim B Freidin, Yakov A Tsepilov, Ian B Stanaway, Weihua Meng, Caroline Hayward, Blair H Smith, Samar Khoury, Marc Parisien, Andrey Bortsov, Luda Diatchenko, Sigrid Børte, Bendik S Winsvold, Ben M Brumpton, John-Anker Zwart, Yurii S Aulchenko, Pradeep Suri, Williams Frances M K FMK Department of Twin Research and Genetic Epidemiology, School of Life Course Sciences, King's College London, London, United Kingdom., and HUNT All-In Pain.
• Department of Twin Research and Genetic Epidemiology, School of Life Course Sciences, King's College London, London, United Kingdom.
• Pain. 2021 Apr 1; 162 (4): 1176-1187.

AbstractSex differences for chronic back pain (cBP) have been reported, with females usually exhibiting greater morbidity, severity, and poorer response to treatment. Genetic factors acting in an age-specific manner have been implicated but never comprehensively explored. We performed sex- and age-stratified genome-wide association study and single nucleotide polymorphism-by-sex interaction analysis for cBP defined as "Back pain for 3+ months" in 202,077 males and 237,754 females of European ancestry from UK Biobank. Two and 7 nonoverlapping genome-wide significant loci were identified for males and females, respectively. A male-specific locus on chromosome 10 near SPOCK2 gene was replicated in 4 independent cohorts. Four loci demonstrated single nucleotide polymorphism-by-sex interaction, although none of them were formally replicated. Single nucleotide polymorphism-explained heritability was higher in females (0.079 vs 0.067, P = 0.006). There was a high, although not complete, genetic correlation between the sexes (r = 0.838 ± 0.041, different from 1 with P = 7.8E-05). Genetic correlation between the sexes for cBP decreased with age (0.858 ± 0.049 in younger people vs 0.544 ± 0.157 in older people; P = 4.3E-05). There was a stronger genetic correlation of cBP with self-reported diagnosis of intervertebral disk degeneration in males than in females (0.889 vs 0.638; P = 3.7E-06). Thus, the genetic component of cBP in the UK Biobank exhibits a mild sex- and age-dependency. This provides an insight into the possible causes of sex- and age-specificity in epidemiology and pathophysiology of cBP and chronic pain at other anatomical sites.Copyright © 2020 International Association for the Study of Pain.

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