A multi-cohort study of polymorphisms in the GH/IGF axis and physical capability: the HALCyon programme

Tamuno Alfred, Yoav Ben-Shlomo, Rachel Cooper, Rebecca Hardy, Cyrus Cooper, Ian J Deary, Tom R Gaunt, David Gunnell, Sarah E Harris, Meena Kumari, Richard M Martin, Avan Aihie Sayer, John M Starr, Diana Kuh, Ian N M Day, HALCyon Study Team, Leone Craig

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Abstract

Background

Low muscle mass and function have been associated with poorer indicators of physical capability in older people, which are in-turn associated with increased mortality rates. The growth hormone/insulin-like growth factor (GH/IGF) axis is involved in muscle function and genetic variants in genes in the axis may influence measures of physical capability.

Methods

As part of the Healthy Ageing across the Life Course (HALCyon) programme, men and women from seven UK cohorts aged between 52 and 90 years old were genotyped for six polymorphisms: rs35767 (IGF1), rs7127900 (IGF2), rs2854744 (IGFBP3), rs2943641 (IRS1), rs2665802 (GH1) and the exon-3 deletion of GHR. The polymorphisms have previously been robustly associated with age-related traits or are potentially functional. Meta-analysis was used to pool within-study genotypic effects of the associations between the polymorphisms and four measures of physical capability: grip strength, timed walk or get up and go, chair rises and standing balance.

Results

Few important associations were observed among the several tests. We found evidence that rs2665802 in GH1 was associated with inability to balance for 5 s (pooled odds ratio per minor allele = 0.90, 95% CI: 0.82–0.98, p-value = 0.01, n = 10,748), after adjusting for age and sex. We found no evidence for other associations between the polymorphisms and physical capability traits.

Conclusion

Our findings do not provide evidence for a substantial influence of these common polymorphisms in the GH/IGF axis on objectively measured physical capability levels in older adults.
Original languageEnglish
Article numbere29883
Number of pages10
JournalPloS ONE
Volume7
Issue number1
DOIs
Publication statusPublished - 10 Jan 2012

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somatomedins
Somatomedins
Polymorphism
cohort studies
somatotropin
Growth Hormone
Cohort Studies
genetic polymorphism
Muscles
Hand Strength
Meta-Analysis
Exons
Alleles
Odds Ratio
Muscle
Mortality
muscles
Genes
meta-analysis
odds ratio

Keywords

  • adult
  • aged
  • aged, 80 and over
  • aging
  • anthropometry
  • cohort studies
  • female
  • gene frequency
  • genetic association studies
  • genotyping techniques
  • Great Britain
  • hand strength
  • health
  • human growth hormone
  • humans
  • insulin-like growth factor I
  • insulin-like growth factor II
  • male
  • middle aged
  • motor activity
  • polymorphism, single nucleotide
  • postural balance
  • sex characteristics
  • signal transduction

Cite this

A multi-cohort study of polymorphisms in the GH/IGF axis and physical capability : the HALCyon programme. / Alfred, Tamuno; Ben-Shlomo, Yoav; Cooper, Rachel; Hardy, Rebecca; Cooper, Cyrus; Deary, Ian J; Gaunt, Tom R; Gunnell, David; Harris, Sarah E; Kumari, Meena; Martin, Richard M; Sayer, Avan Aihie; Starr, John M; Kuh, Diana; Day, Ian N M; HALCyon Study Team ; Craig, Leone.

In: PloS ONE, Vol. 7, No. 1, e29883, 10.01.2012.

Research output: Contribution to journalArticle

Alfred, T, Ben-Shlomo, Y, Cooper, R, Hardy, R, Cooper, C, Deary, IJ, Gaunt, TR, Gunnell, D, Harris, SE, Kumari, M, Martin, RM, Sayer, AA, Starr, JM, Kuh, D, Day, INM, HALCyon Study Team & Craig, L 2012, 'A multi-cohort study of polymorphisms in the GH/IGF axis and physical capability: the HALCyon programme', PloS ONE, vol. 7, no. 1, e29883. https://doi.org/10.1371/journal.pone.0029883
Alfred, Tamuno ; Ben-Shlomo, Yoav ; Cooper, Rachel ; Hardy, Rebecca ; Cooper, Cyrus ; Deary, Ian J ; Gaunt, Tom R ; Gunnell, David ; Harris, Sarah E ; Kumari, Meena ; Martin, Richard M ; Sayer, Avan Aihie ; Starr, John M ; Kuh, Diana ; Day, Ian N M ; HALCyon Study Team ; Craig, Leone. / A multi-cohort study of polymorphisms in the GH/IGF axis and physical capability : the HALCyon programme. In: PloS ONE. 2012 ; Vol. 7, No. 1.
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abstract = "BackgroundLow muscle mass and function have been associated with poorer indicators of physical capability in older people, which are in-turn associated with increased mortality rates. The growth hormone/insulin-like growth factor (GH/IGF) axis is involved in muscle function and genetic variants in genes in the axis may influence measures of physical capability.MethodsAs part of the Healthy Ageing across the Life Course (HALCyon) programme, men and women from seven UK cohorts aged between 52 and 90 years old were genotyped for six polymorphisms: rs35767 (IGF1), rs7127900 (IGF2), rs2854744 (IGFBP3), rs2943641 (IRS1), rs2665802 (GH1) and the exon-3 deletion of GHR. The polymorphisms have previously been robustly associated with age-related traits or are potentially functional. Meta-analysis was used to pool within-study genotypic effects of the associations between the polymorphisms and four measures of physical capability: grip strength, timed walk or get up and go, chair rises and standing balance.ResultsFew important associations were observed among the several tests. We found evidence that rs2665802 in GH1 was associated with inability to balance for 5 s (pooled odds ratio per minor allele = 0.90, 95{\%} CI: 0.82–0.98, p-value = 0.01, n = 10,748), after adjusting for age and sex. We found no evidence for other associations between the polymorphisms and physical capability traits.ConclusionOur findings do not provide evidence for a substantial influence of these common polymorphisms in the GH/IGF axis on objectively measured physical capability levels in older adults.",
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T1 - A multi-cohort study of polymorphisms in the GH/IGF axis and physical capability

T2 - the HALCyon programme

AU - Alfred, Tamuno

AU - Ben-Shlomo, Yoav

AU - Cooper, Rachel

AU - Hardy, Rebecca

AU - Cooper, Cyrus

AU - Deary, Ian J

AU - Gaunt, Tom R

AU - Gunnell, David

AU - Harris, Sarah E

AU - Kumari, Meena

AU - Martin, Richard M

AU - Sayer, Avan Aihie

AU - Starr, John M

AU - Kuh, Diana

AU - Day, Ian N M

AU - HALCyon Study Team

AU - Craig, Leone

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N2 - BackgroundLow muscle mass and function have been associated with poorer indicators of physical capability in older people, which are in-turn associated with increased mortality rates. The growth hormone/insulin-like growth factor (GH/IGF) axis is involved in muscle function and genetic variants in genes in the axis may influence measures of physical capability.MethodsAs part of the Healthy Ageing across the Life Course (HALCyon) programme, men and women from seven UK cohorts aged between 52 and 90 years old were genotyped for six polymorphisms: rs35767 (IGF1), rs7127900 (IGF2), rs2854744 (IGFBP3), rs2943641 (IRS1), rs2665802 (GH1) and the exon-3 deletion of GHR. The polymorphisms have previously been robustly associated with age-related traits or are potentially functional. Meta-analysis was used to pool within-study genotypic effects of the associations between the polymorphisms and four measures of physical capability: grip strength, timed walk or get up and go, chair rises and standing balance.ResultsFew important associations were observed among the several tests. We found evidence that rs2665802 in GH1 was associated with inability to balance for 5 s (pooled odds ratio per minor allele = 0.90, 95% CI: 0.82–0.98, p-value = 0.01, n = 10,748), after adjusting for age and sex. We found no evidence for other associations between the polymorphisms and physical capability traits.ConclusionOur findings do not provide evidence for a substantial influence of these common polymorphisms in the GH/IGF axis on objectively measured physical capability levels in older adults.

AB - BackgroundLow muscle mass and function have been associated with poorer indicators of physical capability in older people, which are in-turn associated with increased mortality rates. The growth hormone/insulin-like growth factor (GH/IGF) axis is involved in muscle function and genetic variants in genes in the axis may influence measures of physical capability.MethodsAs part of the Healthy Ageing across the Life Course (HALCyon) programme, men and women from seven UK cohorts aged between 52 and 90 years old were genotyped for six polymorphisms: rs35767 (IGF1), rs7127900 (IGF2), rs2854744 (IGFBP3), rs2943641 (IRS1), rs2665802 (GH1) and the exon-3 deletion of GHR. The polymorphisms have previously been robustly associated with age-related traits or are potentially functional. Meta-analysis was used to pool within-study genotypic effects of the associations between the polymorphisms and four measures of physical capability: grip strength, timed walk or get up and go, chair rises and standing balance.ResultsFew important associations were observed among the several tests. We found evidence that rs2665802 in GH1 was associated with inability to balance for 5 s (pooled odds ratio per minor allele = 0.90, 95% CI: 0.82–0.98, p-value = 0.01, n = 10,748), after adjusting for age and sex. We found no evidence for other associations between the polymorphisms and physical capability traits.ConclusionOur findings do not provide evidence for a substantial influence of these common polymorphisms in the GH/IGF axis on objectively measured physical capability levels in older adults.

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KW - aged

KW - aged, 80 and over

KW - aging

KW - anthropometry

KW - cohort studies

KW - female

KW - gene frequency

KW - genetic association studies

KW - genotyping techniques

KW - Great Britain

KW - hand strength

KW - health

KW - human growth hormone

KW - humans

KW - insulin-like growth factor I

KW - insulin-like growth factor II

KW - male

KW - middle aged

KW - motor activity

KW - polymorphism, single nucleotide

KW - postural balance

KW - sex characteristics

KW - signal transduction

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DO - 10.1371/journal.pone.0029883

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