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A Multi-Cohort Study of Polymorphisms in the GH/IGF Axis and Physical Capability: The HALCyon Programme

Alfred, T; Ben-Shlomo, Y; Cooper, R; Hardy, R; Cooper, C; Deary, IJ; Gaunt, TR; ... Team, HS; + view all (2012) A Multi-Cohort Study of Polymorphisms in the GH/IGF Axis and Physical Capability: The HALCyon Programme. PLOS ONE , 7 (1) , Article e29883. 10.1371/journal.pone.0029883. Green open access

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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.

Type: Article
Title: A Multi-Cohort Study of Polymorphisms in the GH/IGF Axis and Physical Capability: The HALCyon Programme
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pone.0029883
Publisher version: http://dx.doi.org/10.1371/journal.pone.0029883
Language: English
Additional information: © 2012 Alfred et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The authors acknowledge the support of Medical Research Council (MRC) and Arthritis Research (United Kingdom). Boyd Orr Funding: The Boyd Orr DNA bank was funded by the Wellcome Trust (Grant number: GR068468MA). Follow-up of the Boyd Orr cohort was supported by grants from the Wellcome Trust, World Cancer Research Fund, Research into Ageing and the British Heart Foundation. The Caerphilly Prospective study was funded by the MRC of the United Kingdom. Samples from the English Longitudinal Study of Ageing DNA Repository, received support under a grant (AG1764406S1) awarded by the National Institute on Ageing (NIA). The Hertfordshire Cohort Study and the Hertfordshire Ageing Study were funded by the MRC and the University of Southampton. Lothian Birth Cohort 1921: The Biotechnology and Biological Sciences Research Council (BBSRC) funded the phenotypic data collection and DNA preparation (project grant 15/SAG09977) and genome-wide association study (project grant BB/F019394/1). The work was undertaken by The University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, part of the cross council Lifelong Health a'd Wellbeing Initiative (Centre grant G0700704/84698). Funding from the BBSRC, Engineering and Physical Sciences Research Council, Economic and Social Research Council (ESRC) and MRC is gratefully acknowledged. The MRC National Survey of Health and development is funded by the United Kingdom MRC. HALCyon is funded by the New Dynamics of Ageing cross council research programme. DG is a National Institute of Health Research Senior Investigator. RC receives support from the HALCyon programme funded by the New Dynamics of Ageing (RES-353-25-0001). DK and RH are supported by the United Kingdom MRC. MK is supported by NIA, National Institutes of Health (AG1764406S1). TA is an ESRC PhD student. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Education
UCL > Provost and Vice Provost Offices > School of Education > UCL Institute of Education
UCL > Provost and Vice Provost Offices > School of Education > UCL Institute of Education > IOE - Social Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute of Cardiovascular Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute of Epidemiology and Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute of Epidemiology and Health > Epidemiology and Public Health
URI: https://discovery.ucl.ac.uk/id/eprint/1342992
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