TY - JOUR
T1 - Genetics of hand grip strength in mid to late life
AU - Chan, Jessica P. L.
AU - Thalamuthu, Anbupalam
AU - Oldmeadow, Christopher
AU - Armstrong, Nicola J.
AU - Holliday, Elizabeth G.
AU - McEvoy, Mark
AU - Kwok, John B.
AU - Assareh, Amelia A.
AU - Peel, Rosanne
AU - Hancock, Stephen J.
AU - Reppermund, Simone
AU - Menant, Jasmine
AU - Trollor, Julian N.
AU - Brodaty, Henry
AU - Schofield, Peter R.
AU - Attia, John R.
AU - Sachdev, Perminder S.
AU - Scott, Rodney J.
AU - Mather, Karen A.
PY - 2015/2
Y1 - 2015/2
N2 - Hand grip strength (GS) is a predictor of mortality in older adults and is moderately to highly heritable, but no genetic variants have been consistently identified. We aimed to identify single nucleotide polymorphisms (SNPs) associated with GS in middle-aged to older adults using a genome-wide association study (GWAS). GS was measured using handheld dynamometry in community-dwelling men and women aged 55-85 from the Hunter Community Study (HCS, N = 2088) and the Sydney Memory and Ageing Study (Sydney MAS, N = 541). Genotyping was undertaken using Affymetrix microarrays with imputation to HapMap2. Analyses were performed using linear regression. No genome-wide significant results were observed in HCS nor were any of the top signals replicated in Sydney MAS. Gene-based analyses in HCS identified two significant genes (ZNF295, C2CD2), but these results were not replicated in Sydney MAS. One out of eight SNPs previously associated with GS, rs550942, located near the CNTF gene, was significantly associated with GS (p = 0.005) in the HCS cohort only. Study differences may explain the lack of consistent results between the studies, including the smaller sample size of the Sydney MAS cohort. Our modest sample size also had limited power to identify variants of small effect. Our results suggest that similar to various other complex traits, many genetic variants of small effect size may influence GS. Future GWAS using larger samples and consistent measures may prove more fruitful at identifying genetic contributors for GS in middle-aged to older adults.
AB - Hand grip strength (GS) is a predictor of mortality in older adults and is moderately to highly heritable, but no genetic variants have been consistently identified. We aimed to identify single nucleotide polymorphisms (SNPs) associated with GS in middle-aged to older adults using a genome-wide association study (GWAS). GS was measured using handheld dynamometry in community-dwelling men and women aged 55-85 from the Hunter Community Study (HCS, N = 2088) and the Sydney Memory and Ageing Study (Sydney MAS, N = 541). Genotyping was undertaken using Affymetrix microarrays with imputation to HapMap2. Analyses were performed using linear regression. No genome-wide significant results were observed in HCS nor were any of the top signals replicated in Sydney MAS. Gene-based analyses in HCS identified two significant genes (ZNF295, C2CD2), but these results were not replicated in Sydney MAS. One out of eight SNPs previously associated with GS, rs550942, located near the CNTF gene, was significantly associated with GS (p = 0.005) in the HCS cohort only. Study differences may explain the lack of consistent results between the studies, including the smaller sample size of the Sydney MAS cohort. Our modest sample size also had limited power to identify variants of small effect. Our results suggest that similar to various other complex traits, many genetic variants of small effect size may influence GS. Future GWAS using larger samples and consistent measures may prove more fruitful at identifying genetic contributors for GS in middle-aged to older adults.
KW - hand grip strength
KW - genetics
KW - GWAS
KW - ageing
UR - http://www.scopus.com/inward/record.url?scp=84922221828&partnerID=8YFLogxK
U2 - 10.1007/s11357-015-9745-5
DO - 10.1007/s11357-015-9745-5
M3 - Article
C2 - 25637336
AN - SCOPUS:84922221828
SN - 0161-9152
VL - 37
SP - 1
EP - 10
JO - Age (Dordrecht, Netherlands)
JF - Age (Dordrecht, Netherlands)
IS - 1
M1 - 3
ER -