Sex- and age-specific genetic analysis of chronic back pain

被引：22

作者：

Freidin, Maxim B. ^{[1
]}

Tsepilov, Yakov A. ^{[2
,3
]}

Stanaway, Ian B. ^{[4
]}

Meng, Weihua ^{[5
,6
]}

Hayward, Caroline ^{[7
]}

Smith, Blair H. ^{[5
,6
]}

Khoury, Samar ^{[8
,9
,10
]}

Parisien, Marc ^{[8
,9
,10
]}

Bortsov, Andrey ^{[11
]}

Diatchenko, Luda ^{[8
,9
,10
]}

Borte, Sigrid ^{[12
,13
,14
]}

Winsvold, Bendik S. ^{[13
,14
]}

Brumpton, Ben M. ^{[14
]}

Zwart, John-Anker ^{[12
,13
,14
]}

Aulchenko, Yurii S. ^{[2
,3
,15
]}

Suri, Pradeep ^{[16
,17
,18
]}

Williams, Frances M. K. ^{[1
]}

机构：

[1] Kings Coll London, Sch Life Course Sci, Dept Twin Res & Genet Epidemiol, London, England

[2] Novosibirsk State Univ, Lab Theoret & Appl Funct Genom, Novosibirsk, Russia

[3] Inst Cytol & Genet, Lab Recombinat & Segregat Anal, Novosibirsk, Russia

[4] Univ Washington, Harborview Med Ctr, Sch Med, Div Nephrol, Seattle, WA 98104 USA

[5] Univ Dundee, Ninewells Hosp, Med Res Inst, Div Populat Hlth & Genom, Dundee, Scotland

[6] Univ Dundee, Sch Med, Dundee, Scotland

[7] Univ Edinburgh, Western Gen Hosp, Inst Genet & Mol Med, Med Res Council,Human Genet Unit, Edinburgh, Midlothian, Scotland

[8] McGill Univ, Alan Edwards Ctr Res Pain, Montreal, PQ, Canada

[9] McGill Univ, Dept Anesthesia, Montreal, PQ, Canada

[10] McGill Univ, Sch Dent, Montreal, PQ, Canada

[11] Duke Univ, Ctr Translat Pain Med, Dept Anesthesiol, Durham, NC USA

[12] Univ Oslo, Fac Med, Inst Clin Med, Oslo, Norway

[13] Oslo Univ Hosp, Dept Res Innovat & Educ, Div Clin Neurosci, Oslo, Norway

[14] Norwegian Univ Sci & Technol, Fac Med & Hlth Sci, KG Jebsen Ctr Genet Epidemiol, Dept Publ Hlth & Nursing, Trondheim, Norway

[15] PolyOmica, S Hertogenbosh, Netherlands

[16] VA Puget Sound Hlth Care Syst, Div Rehabil Care Serv, Seattle Epidemiol Res & Informat Ctr ERIC, Seattle, WA USA

[17] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA

[18] Univ Washington, Clin Learning Evidence & Res CLEAR Ctr, Seattle, WA 98195 USA

来源：

PAIN | 2021年 / 162卷 / 04期

基金：

英国经济与社会研究理事会; 俄罗斯基础研究基金会; 美国国家卫生研究院; 英国惠康基金; 英国医学研究理事会;

关键词：

chronic back pain; SNP-by-sex interaction; gene-environment interaction; heritability; genome-wide association study; LD SCORE REGRESSION; COHORT PROFILE; FLIP-FLOP; PREVALENCE; HERITABILITY; POPULATION; DISEASES; GENDER; EPIDEMIOLOGY; ARCHITECTURE;

D O I：

10.1097/j.pain.0000000000002100

中图分类号：

R614 [麻醉学];

学科分类号：

100217 ;

摘要：

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.

引用

页码：1176 / 1187

页数：12

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