Integrated genetic analyses revealed novel human longevity loci and reduced risks of multiple diseases in a cohort study of 15,651 Chinese individuals.
Integrated genetic analyses revealed novel human longevity loci and reduced risks of multiple diseases in a cohort study of 15,651 Chinese individuals.
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一项针对 15,651 名中国人的队列研究揭示了新的人类长寿基因座并降低了多种疾病的风险
DOI：
10.1111/acel.13323
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发表时间：
2021-03
期刊：
影响因子：
7.8
通讯作者：
Zeng Y
中科院分区：
文献类型：
--
作者：
Liu X;Song Z;Li Y;Yao Y;Fang M;Bai C;An P;Chen H;Chen Z;Tang B;Shen J;Gao X;Zhang M;Chen P;Zhang T;Jia H;Liu X;Hou Y;Yang H;Wang J;Wang F;Xu X;Min J;Nie C;Zeng Y
人们对研究长寿的遗传贡献越来越感兴趣，但已确定的相关基因有限。在这项研究中，我们对15,651名中国人进行了长寿的遗传关联研究。在对11，045名个体的病例对照分析中确定了新的长寿基因座BMPER（rs 17169634; p = 7.91 × 10−15）和TMEM 43/XPC（rs 1043943; p = 3.59 × 10−8）。BRAF（rs 1267601; p = 8.33 × 10−15）和BMPER（rs 17169634; p = 1.45 × 10−10）与12,664名有生存状态记录的个体的预期寿命显著相关。额外的性别分层分析确定了性别特异性长寿基因。值得注意的是，在TOMM 40/APOE区域的两个连锁不平衡区组中鉴定出了性别差异关联，表明雄性和雌性之间减数分裂期间存在潜在差异。此外，多基因风险评分和孟德尔随机化分析显示，长寿与多种疾病（如2型糖尿病、心血管疾病和关节炎）的风险降低存在遗传因果关系。最后，我们结合了遗传标记、疾病状态和生活方式来对长寿或非长寿人群进行分类，并预测寿命。我们的预测模型表现出良好的性能（AUC = 0.86的寿命分类和解释19.8%的寿命方差），并提出了一个更大的预测效率在女性比男性。总之，我们的发现不仅揭示了遗传对长寿的贡献，而且阐明了疾病与长寿之间的相关性。
There is growing interest in studying the genetic contributions to longevity, but limited relevant genes have been identified. In this study, we performed a genetic association study of longevity in a total of 15,651 Chinese individuals. Novel longevity loci, BMPER (rs17169634; p = 7.91 × 10−15) and TMEM43/XPC (rs1043943; p = 3.59 × 10−8), were identified in a case–control analysis of 11,045 individuals. BRAF (rs1267601; p = 8.33 × 10−15) and BMPER (rs17169634; p = 1.45 × 10−10) were significantly associated with life expectancy in 12,664 individuals who had survival status records. Additional sex‐stratified analyses identified sex‐specific longevity genes. Notably, sex‐differential associations were identified in two linkage disequilibrium blocks in the TOMM40/APOE region, indicating potential differences during meiosis between males and females. Moreover, polygenic risk scores and Mendelian randomization analyses revealed that longevity was genetically causally correlated with reduced risks of multiple diseases, such as type 2 diabetes, cardiovascular diseases, and arthritis. Finally, we incorporated genetic markers, disease status, and lifestyles to classify longevity or not‐longevity groups and predict life span. Our predictive models showed good performance (AUC = 0.86 for longevity classification and explained 19.8% variance of life span) and presented a greater predictive efficiency in females than in males. Taken together, our findings not only shed light on the genetic contributions to longevity but also elucidate correlations between diseases and longevity.
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DOI：
10.1093/bioinformatics/btu848
发表时间：
2015-05-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Euesden J;Lewis CM;O'Reilly PF
通讯作者：
O'Reilly PF
影响因子：
11
作者：
Davies G;Harris SE;Reynolds CA;Payton A;Knight HM;Liewald DC;Lopez LM;Luciano M;Gow AJ;Corley J;Henderson R;Murray C;Pattie A;Fox HC;Redmond P;Lutz MW;Chiba-Falek O;Linnertz C;Saith S;Haggarty P;McNeill G;Ke X;Ollier W;Horan M;Roses AD;Ponting CP;Porteous DJ;Tenesa A;Pickles A;Starr JM;Whalley LJ;Pedersen NL;Pendleton N;Visscher PM;Deary IJ
通讯作者：
Deary IJ
DOI：
10.1073/pnas.0400848101
发表时间：
2004-05-25
影响因子：
11.1
作者：
Huang, C;Xiong, CJ;Kornfeld, K
通讯作者：
Kornfeld, K
DOI：
10.1093/gerona/glr223
发表时间：
2012-04-01
影响因子：
5.1
作者：
Andersen, Stacy L.;Sebastiani, Paola;Perls, Thomas T.
通讯作者：
Perls, Thomas T.
DOI：
10.1196/annals.1386.051
发表时间：
2006-01-01
期刊：
ESTROGENS AND HUMAN DISEASES
影响因子：
--
作者：
Candore, Giuseppina;Balistreri, Carmela R.;Caruso, Calogero
通讯作者：
Caruso, Calogero