Papers of the Week

Sex 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 GWAS and SNP-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 seven non-overlapping genome-wide significant loci were identified for males and females, respectively. A male-specific locus on chromosome 10 near SPOCK2 gene was replicated in four independent cohorts. Four loci demonstrated SNP-by-sex interaction, although none of them were formally replicated. SNP-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 disc 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.