期刊
PAIN
卷 162, 期 4, 页码 1176-1187出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/j.pain.0000000000002100
关键词
chronic back pain; SNP-by-sex interaction; gene-environment interaction; heritability; genome-wide association study
资金
- Russian Ministry of Education and Science under the 5 to 100 Excellence Programme
- Federal Agency of Scientific Organizations via the Institute of Cytology and Genetics [0324-2019-0040-C-01/AAAA-17-117092070032-4]
- Russian Foundation for Basic Research [19-015-00151]
- Canadian Excellence Research Chairs Program [CERC9]
- MRC University Unit Programme [MC_UU_00007/10]
- Chief Scientist Office of the Scottish Government Health Directorates [CZD/16/6]
- Scottish Funding Council [HR03006]
- Medical Research Council UK
- Wellcome Trust (Wellcome Trust Strategic Award Stratifying Resilience and Depression Longitudinally [STRADL]) [104036/Z/14/Z]
- National Institute of Dental and Craniofacial Research (NIDCR) [U01DE017018]
- NIDCR [HHSN268201200008I]
- Economic and Social Research Council
- National Institute on Ageing
- ESRC
- Wellcome
- MRC [MR/N01104X/1, ES/S008349/1]
- National Institutes of Health (NIH)
- University of Michigan
- Norwegian Research council
- Central Norway Regional Health Authority
- Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU)
- Wellcome Trust (Wellcome Trust Strategic Award Stratifying Resilience and Depression Longitudinally [STRADL])
- Medical Research Council [MR/N01104X/1] Funding Source: researchfish
- MRC [MC_UU_00007/10] Funding Source: UKRI
Sex differences exist in chronic back pain (cBP), with females usually experiencing higher morbidity, severity, and poorer treatment response. Genetic factors may play a role in an age-specific manner, with a high genetic correlation between the sexes in cBP.
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 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.
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