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中老年握力的遗传学研究

Genetics of hand grip strength in mid to late life.

作者信息

Chan Jessica P L, Thalamuthu Anbupalam, Oldmeadow Christopher, Armstrong Nicola J, Holliday Elizabeth G, McEvoy Mark, Kwok John B, Assareh Amelia A, Peel Rosanne, Hancock Stephen J, Reppermund Simone, Menant Jasmine, Trollor Julian N, Brodaty Henry, Schofield Peter R, Attia John R, Sachdev Perminder S, Scott Rodney J, Mather Karen A

机构信息

Centre for Healthy Brain Ageing, Psychiatry, University of New South Wales (UNSW), NPI, Euroa Centre, Barker St, Randwick, Sydney, NSW, 2031, Australia.

出版信息

Age (Dordr). 2015 Feb;37(1):9745. doi: 10.1007/s11357-015-9745-5. Epub 2015 Feb 1.

Abstract

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.

摘要

握力(GS)是老年人死亡率的一个预测指标,具有中度到高度的遗传性,但尚未一致鉴定出相关基因变异。我们旨在通过全基因组关联研究(GWAS),在中年至老年人群中鉴定与握力相关的单核苷酸多态性(SNP)。采用手持测力计对来自亨特社区研究(HCS,N = 2088)和悉尼记忆与衰老研究(悉尼MAS,N = 541)的55 - 85岁社区居住男性和女性进行握力测量。使用Affymetrix微阵列进行基因分型,并推算至HapMap2。采用线性回归进行分析。在HCS中未观察到全基因组显著结果,悉尼MAS中也未重复出任何顶级信号。HCS中的基因分型分析鉴定出两个显著基因(ZNF295、C2CD2),但这些结果在悉尼MAS中未得到重复。先前与握力相关的8个SNP中的一个,rs550942,位于CNTF基因附近,仅在HCS队列中与握力显著相关(p = 0.005)。研究差异可能解释了各研究结果缺乏一致性的原因,包括悉尼MAS队列样本量较小。我们适度的样本量识别小效应变异的能力也有限。我们的结果表明,与其他各种复杂性状类似,许多小效应大小的基因变异可能影响握力。未来使用更大样本和一致测量方法的GWAS可能在鉴定中年至老年人群握力的遗传贡献因素方面更有成效。

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Genetics of hand grip strength in mid to late life.中老年握力的遗传学研究
Age (Dordr). 2015 Feb;37(1):9745. doi: 10.1007/s11357-015-9745-5. Epub 2015 Feb 1.

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