GWAS analysis of handgrip and lower body strength in older adults in the CHARGE consortium.
GWAS analysis of handgrip and lower body strength in older adults in the CHARGE consortium.
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DOI：
10.1111/acel.12468
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发表时间：
2016-10
期刊：
影响因子：
7.8
通讯作者：
Murabito JM
中科院分区：
文献类型：
--
作者：
Matteini AM;Tanaka T;Karasik D;Atzmon G;Chou WC;Eicher JD;Johnson AD;Arnold AM;Callisaya ML;Davies G;Evans DS;Holtfreter B;Lohman K;Lunetta KL;Mangino M;Smith AV;Smith JA;Teumer A;Yu L;Arking DE;Buchman AS;Chibinik LB;De Jager PL;Evans DA;Faul JD;Garcia ME;Gillham-Nasenya I;Gudnason V;Hofman A;Hsu YH;Ittermann T;Lahousse L;Liewald DC;Liu Y;Lopez L;Rivadeneira F;Rotter JI;Siggeirsdottir K;Starr JM;Thomson R;Tranah GJ;Uitterlinden AG;Völker U;Völzke H;Weir DR;Yaffe K;Zhao W;Zhuang WV;Zmuda JM;Bennett DA;Cummings SR;Deary IJ;Ferrucci L;Harris TB;Kardia SL;Kocher T;Kritchevsky SB;Psaty BM;Seshadri S;Spector TD;Srikanth VK;Windham BG;Zillikens MC;Newman AB;Walston JD;Kiel DP;Murabito JM
随着年龄的增长，肌肉力量的下降是老年人健康轨迹的重要预测指标。包括遗传在内的几个因素被认为是肌肉力量变化的原因。为了确定肌肉力量的遗传因素，对握力的全基因组关联研究进行了荟萃分析。握力测量使用手持式测力仪测量了来自14个队列研究的27581名65岁以上欧洲血统的个体。对约270万个输入和基因型变异（snp）进行了全基因组关联分析。使用来自三个队列的6393个人的数据进行了最重要的发现的复制。下体力量的GWAS在一个子集队列中也具有特征。从发现队列的荟萃分析中观察到2个全基因组显著（P值< 5 × 10−8）和39个提示（P值< 5 × 10−5）关联。与复制队列进行meta分析后，8号染色体上rs752045基因在全基因组范围内显著相关（β = 0.47, SE = 0.08， P值= 5.20 × 10−10）。该SNP被定位到一个基因间区域，位于从人类骨骼肌成肌细胞系分化的骨骼肌肌管中一个可接近的染色质区域（dna酶超敏位点）。该位点改变了与肌肉修复机制有关的CCAAT/增强子结合蛋白β (CEBPB)的结合基序。下肢力量的GWAS没有产生显著的结果。调节肌管分化和肌肉修复的染色体区域的常见遗传变异可能导致老年人握力的变化。需要进一步的研究来揭示这种基因变异与肌肉力量之间的联系机制。
Decline in muscle strength with aging is an important predictor of health trajectory in the elderly. Several factors, including genetics, are proposed contributors to variability in muscle strength. To identify genetic contributors to muscle strength, a meta‐analysis of genomewide association studies of handgrip was conducted. Grip strength was measured using a handheld dynamometer in 27 581 individuals of European descent over 65 years of age from 14 cohort studies. Genomewide association analysis was conducted on ~2.7 million imputed and genotyped variants (SNPs). Replication of the most significant findings was conducted using data from 6393 individuals from three cohorts. GWAS of lower body strength was also characterized in a subset of cohorts. Two genomewide significant (P‐value< 5 × 10−8) and 39 suggestive (P‐value< 5 × 10−5) associations were observed from meta‐analysis of the discovery cohorts. After meta‐analysis with replication cohorts, genomewide significant association was observed for rs752045 on chromosome 8 (β = 0.47, SE = 0.08, P‐value = 5.20 × 10−10). This SNP is mapped to an intergenic region and is located within an accessible chromatin region (DNase hypersensitivity site) in skeletal muscle myotubes differentiated from the human skeletal muscle myoblasts cell line. This locus alters a binding motif of the CCAAT/enhancer‐binding protein‐β (CEBPB) that is implicated in muscle repair mechanisms. GWAS of lower body strength did not yield significant results. A common genetic variant in a chromosomal region that regulates myotube differentiation and muscle repair may contribute to variability in grip strength in the elderly. Further studies are needed to uncover the mechanisms that link this genetic variant with muscle strength.
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影响因子：
9.8
作者：
ENCODE Project Consortium
通讯作者：
ENCODE Project Consortium
遗传多态性对非常老年功能状态的贡献：基于基因的氧化应激途径中38个基因（311 SNP）的分析。
影响因子：
3.9
作者：
Dato, S.;Soerensen, M.;Lagani, V.;Montesanto, A.;Passarino, G.;Christensen, K.;Tan, Q.;Christiansen, L.
通讯作者：
Christiansen, L.
影响因子：
14.9
作者：
Ward LD;Kellis M
通讯作者：
Kellis M
影响因子：
120.7
作者：
Willcox, Bradley J.;He, Qimei;Curb, J. David
通讯作者：
Curb, J. David
影响因子：
120.7
作者：
Rantanen, T;Guralnik, JM;White, L
通讯作者：
White, L