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

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; Frances M.K. Williams

doi:10.1097/j.pain.0000000000002100

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

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, Frances M.K. Williams

Research output: Journal Publication › Article › peer-review

19 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	1176-1187
Number of pages	12
Journal	Pain
Volume	162
Issue number	4
DOIs	https://doi.org/10.1097/j.pain.0000000000002100
Publication status	Published - 1 Apr 2021
Externally published	Yes

ASJC Scopus subject areas

Neurology
Clinical Neurology
Anesthesiology and Pain Medicine

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1097/j.pain.0000000000002100

Cite this

Freidin, M. B., Tsepilov, Y. A., Stanaway, I. B., Meng, W., Hayward, C., Smith, B. H., Khoury, S., Parisien, M., Bortsov, A., Diatchenko, L., Børte, S., Winsvold, B. S., Brumpton, B. M., Zwart, J. A., Aulchenko, Y. S., Suri, P., & Williams, F. M. K. (2021). Sex-and age-specific genetic analysis of chronic back pain. Pain, 162(4), 1176-1187. https://doi.org/10.1097/j.pain.0000000000002100

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title = "Sex-and age-specific genetic analysis of chronic back pain",

abstract = "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.",

author = "Freidin, {Maxim B.} and Tsepilov, {Yakov A.} and Stanaway, {Ian B.} and Weihua Meng and Caroline Hayward and Smith, {Blair H.} and Samar Khoury and Marc Parisien and Andrey Bortsov and Luda Diatchenko and Sigrid B{\o}rte and Winsvold, {Bendik S.} and Brumpton, {Ben M.} and Zwart, {John Anker} and Aulchenko, {Yurii S.} and Pradeep Suri and Williams, {Frances M.K.}",

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AU - Freidin, Maxim B.

AU - Tsepilov, Yakov A.

AU - Stanaway, Ian B.

AU - Meng, Weihua

AU - Hayward, Caroline

AU - Smith, Blair H.

AU - Khoury, Samar

AU - Parisien, Marc

AU - Bortsov, Andrey

AU - Diatchenko, Luda

AU - Børte, Sigrid

AU - Winsvold, Bendik S.

AU - Brumpton, Ben M.

AU - Zwart, John Anker

AU - Aulchenko, Yurii S.

AU - Suri, Pradeep

AU - Williams, Frances M.K.

PY - 2021/4/1

Y1 - 2021/4/1

N2 - 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.

AB - 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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VL - 162

SP - 1176

EP - 1187

JO - Pain

JF - Pain

IS - 4

ER -

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

Abstract

ASJC Scopus subject areas

UN SDGs

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