Genetics of hand grip strength in mid to late life
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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.
KeywordsHand grip strength Genetics GWAS Ageing
We would like to acknowledge and thank the HCS and Sydney MAS participants, their supporters and their research teams. This work was supported by various agencies. Sydney MAS is supported by the Australian National Health and Medical Research Council (NHMRC) Program Grants 350833 and 568969. For Sydney MAS, DNA was extracted by Genetic Repositories Australia, an Enabling Facility supported by the NHMRC Grant 401184. The HCS is supported by the University of Newcastle, the Gladys M Brawn Senior Research Fellowship Scheme and the Fairfax Family Foundation. Henry Brodaty is partly supported by the NHMRC-funded Dementia Collaborative Research Centre at the University of New South Wales. Nicola Armstrong is supported by the NHMRC Project Grant 525453, and Karen Mather is supported by an Alzheimer’s Australia Dementia Research Foundation Postdoctoral Fellowship and NHMRC Capacity Building Grant 568940. Amelia Assareh was supported by a PhD scholarship from the Dementia Collaborative Research Centre, UNSW. Elizabeth Holliday is supported by the Australian Heart Foundation and National Stroke Foundation (100071).
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