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

doi:10.1371/journal.pone.0029883

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

^*Corresponding author for this work

Research output: Contribution to journal › Article (Academic Journal) › peer-review

11 Citations (Scopus)

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% Cl: 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 language	English
Article number	e29883
Pages (from-to)	186-195
Number of pages	10
Journal	PLoS ONE
Volume	7
Issue number	1
DOIs	https://doi.org/10.1371/journal.pone.0029883
Publication status	Published - 10 Jan 2012

Keywords

GH1 GENE
PROSTATE-CANCER RISK
GENOME-WIDE ASSOCIATION
HUMAN GROWTH-HORMONE
INSULIN-RESISTANCE
SKELETAL-MUSCLE MASS
IGF-I
COMMON VARIATION
INSULIN-LIKE-GROWTH-FACTOR-2 GENE
ADULT HEIGHT

Access to Document

10.1371/journal.pone.0029883

Handle.net

Persistent link

Cite this

Alfred, T., Ben-Shlomo, Y., Cooper, R., Hardy, R., Cooper, C., Deary, I. J., Gaunt, T. R., Gunnell, D., Harris, S. E., Kumari, M., Martin, R. M., Sayer, A. A., Starr, J. M., Kuh, D., & Day, I. N. M. (2012). A multi-cohort study of polymorphisms in the GH/IGF axis and physical capability: The HALCyon programme. PLoS ONE, 7(1), 186-195. [e29883]. https://doi.org/10.1371/journal.pone.0029883

@article{c9d28ca23e73456ebedcc6b8879bfe3d,

title = "A multi-cohort study of polymorphisms in the GH/IGF axis and physical capability: The HALCyon programme",

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% Cl: 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.",

keywords = "GH1 GENE, PROSTATE-CANCER RISK, GENOME-WIDE ASSOCIATION, HUMAN GROWTH-HORMONE, INSULIN-RESISTANCE, SKELETAL-MUSCLE MASS, IGF-I, COMMON VARIATION, INSULIN-LIKE-GROWTH-FACTOR-2 GENE, ADULT HEIGHT",

author = "Tamuno Alfred and Yoav Ben-Shlomo and Rachel Cooper and Rebecca Hardy and Cyrus Cooper and Deary, {Ian J.} and Gaunt, {Tom R.} and David Gunnell and Harris, {Sarah E.} and Meena Kumari and Martin, {Richard M.} and Sayer, {Avan Aihie} and Starr, {John M.} and Diana Kuh and Day, {Ian N M}",

year = "2012",

month = jan,

day = "10",

doi = "10.1371/journal.pone.0029883",

language = "English",

volume = "7",

pages = "186--195",

journal = "PLoS ONE",

issn = "1932-6203",

publisher = "Public Library of Science",

number = "1",

}

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 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, pp. 186-195. https://doi.org/10.1371/journal.pone.0029883

TY - JOUR

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

PY - 2012/1/10

Y1 - 2012/1/10

N2 - 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% Cl: 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.

AB - 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% Cl: 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.

KW - GH1 GENE

KW - PROSTATE-CANCER RISK

KW - GENOME-WIDE ASSOCIATION

KW - HUMAN GROWTH-HORMONE

KW - INSULIN-RESISTANCE

KW - SKELETAL-MUSCLE MASS

KW - IGF-I

KW - COMMON VARIATION

KW - INSULIN-LIKE-GROWTH-FACTOR-2 GENE

KW - ADULT HEIGHT

UR - http://www.scopus.com/inward/record.url?scp=84855590669&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0029883

DO - 10.1371/journal.pone.0029883

M3 - Article (Academic Journal)

C2 - 22253814

VL - 7

SP - 186

EP - 195

JO - PLoS ONE

JF - PLoS ONE

SN - 1932-6203

IS - 1

M1 - e29883

ER -

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

Abstract

Keywords

Access to Document

Handle.net

Other files and links

Fingerprint

CENTRE FOR CASUAL ANALYSES IN TRANSLATIONAL EPIDEMIOLOGY (CAiTE)

Cite this

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

Abstract

Keywords

Access to Document

Handle.net

Other files and links

Fingerprint

Projects

CENTRE FOR CASUAL ANALYSES IN TRANSLATIONAL EPIDEMIOLOGY (CAiTE)

Cite this