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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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.


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.


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.


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
Issue number1
Publication statusPublished - 10 Jan 2012


  • 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


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