A genome-wide association study of aging.
A genome-wide association study of aging.
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DOI：
10.1016/j.neurobiolaging.2011.05.026
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发表时间：
2011-11
影响因子：
4.2
通讯作者：
Franceschini N
中科院分区：
文献类型：
--
作者：
Walter S;Atzmon G;Demerath EW;Garcia ME;Kaplan RC;Kumari M;Lunetta KL;Milaneschi Y;Tanaka T;Tranah GJ;Völker U;Yu L;Arnold A;Benjamin EJ;Biffar R;Buchman AS;Boerwinkle E;Couper D;De Jager PL;Evans DA;Harris TB;Hoffmann W;Hofman A;Karasik D;Kiel DP;Kocher T;Kuningas M;Launer LJ;Lohman KK;Lutsey PL;Mackenbach J;Marciante K;Psaty BM;Reiman EM;Rotter JI;Seshadri S;Shardell MD;Smith AV;van Duijn C;Walston J;Zillikens MC;Bandinelli S;Baumeister SE;Bennett DA;Ferrucci L;Gudnason V;Kivimaki M;Liu Y;Murabito JM;Newman AB;Tiemeier H;Franceschini N
人类长寿和健康衰老表现出中等的遗传性（20-50%）。我们对来自基因组流行病学联盟心脏与衰老研究队列的9项全基因组关联研究进行了荟萃分析，得出两个结果：a)全因死亡率和b)无重大疾病或死亡的生存期。单核苷酸多态性（SNP）不是两种结果的全基因组显著预测因子（p < 5 × 10−8）。我们发现14个独立的snp预测死亡风险，8个snp预测无事件生存（p < 10−5）。这些snp位于或靠近大脑中高表达的基因（HECW2, HIP1, BIN2, GRIA1），参与神经发育和功能的基因（KCNQ4, LMO4, GRIA1, NETO1）和自噬（ATG4C），以及与包括癌症和阿尔茨海默病在内的各种疾病风险相关的基因中。除了性状之间有相当大的重叠外，通路和网络分析也证实了这些发现。这些发现表明，参与神经过程的基因变异可能是调节无重大疾病的衰老和实现长寿的重要因素。
Human longevity and healthy aging show moderate heritability (20–50%). We conducted a meta-analysis of genome-wide association studies from nine studies from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium for two outcomes: a) all-cause mortality and b) survival free of major disease or death. No single nucleotide polymorphism (SNP) was a genome-wide significant predictor of either outcome (p < 5 × 10−8). We found fourteen independent SNPs that predicted risk of death, and eight SNPs that predicted event-free survival (p < 10−5). These SNPs are in or near genes that are highly expressed in the brain (HECW2, HIP1, BIN2, GRIA1), genes involved in neural development and function (KCNQ4, LMO4, GRIA1, NETO1) and autophagy (ATG4C), and genes that are associated with risk of various diseases including cancer and Alzheimer’s disease. In addition to considerable overlap between the traits, pathway and network analysis corroborated these findings. These findings indicate that variation in genes involved in neurological processes may be an important factor in regulating aging free of major disease and achieving longevity.
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