Genome-wide meta-analysis of muscle weakness identifies 15 susceptibility loci in older men and women
Genome-wide meta-analysis of muscle weakness identifies 15 susceptibility loci in older men and women
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肌肉无力的全基因组荟萃分析确定了老年男性和女性的 15 个易感位点
DOI：
10.1101/2020.05.14.20100354
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Jones G
中科院分区：
文献类型：
--
作者：
Jones G
肌肉力量低是与老年人发病率和死亡率有关的健康状况不佳的重要遗传指标。在一项来自22个队列的256523名60岁及以上欧洲人的全基因组关联研究荟萃分析中，我们确定了15个与肌肉无力相关的基因座（欧洲老年人肌肉减少症工作组定义：n= 48596例，占总数的18.9%），其中包括12个在之前的握力连续测量分析中未涉及的基因座。据报道，基因座包括参与自身免疫性疾病（HLA-DQA1p= 4 × 10−17）、关节炎（GDF5p= 4 × 10−13）、细胞周期控制和癌症保护、转录调节以及其他参与肌肉骨骼系统发育和维持的基因。使用孟德尔随机化，我们报告了可能重叠的因果通路，包括糖尿病易感性、血液学参数和免疫系统。我们的结论是，老年人的肌肉无力与持续的力量有不同的机制，包括几个被认为是衰老标志的途径。
Low muscle strength is an important heritable indicator of poor health linked to morbidity and mortality in older people. In a genome-wide association study meta-analysis of 256,523 Europeans aged 60 years and over from 22 cohorts we identify 15 loci associated with muscle weakness (European Working Group on Sarcopenia in Older People definition:n= 48,596 cases, 18.9% of total), including 12 loci not implicated in previous analyses of continuous measures of grip strength. Loci include genes reportedly involved in autoimmune disease (HLA-DQA1p= 4 × 10−17), arthritis (GDF5p= 4 × 10−13), cell cycle control and cancer protection, regulation of transcription, and others involved in the development and maintenance of the musculoskeletal system. Using Mendelian randomization we report possible overlapping causal pathways, including diabetes susceptibility, haematological parameters, and the immune system. We conclude that muscle weakness in older adults has distinct mechanisms from continuous strength, including several pathways considered to be hallmarks of ageing.
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影响因子：
30.8
作者：
Bulik-Sullivan, Brendan K.;Loh, Po-Ru;Finucane, Hilary K.;Ripke, Stephan;Yang, Jian;Patterson, Nick;Daly, Mark J.;Price, Alkes L.;Neale, Benjamin M.
通讯作者：
Neale, Benjamin M.
影响因子：
4.2
作者：
Rodriguez, Alexander J.;Lewis, Joshua R.;Prince, Richard L.
通讯作者：
Prince, Richard L.
基因组分析确定了数百种与初潮年龄相关的变异，并支持青春期时机在癌症风险中的作用
DOI：
10.17863/cam.9404
发表时间：
2017
期刊：
--
影响因子：
--
作者：
Day, FR
通讯作者：
Day, FR
影响因子：
4.6
作者：
Nakayama, N;Han, CYE;Zhang, K
通讯作者：
Zhang, K
影响因子：
16.6
作者：
Pattaro C;Teumer A;Gorski M;Chu AY;Li M;Mijatovic V;Garnaas M;Tin A;Sorice R;Li Y;Taliun D;Olden M;Foster M;Yang Q;Chen MH;Pers TH;Johnson AD;Ko YA;Fuchsberger C;Tayo B;Nalls M;Feitosa MF;Isaacs A;Dehghan A;d'Adamo P;Adeyemo A;Dieffenbach AK;Zonderman AB;Nolte IM;van der Most PJ;Wright AF;Shuldiner AR;Morrison AC;Hofman A;Smith AV;Dreisbach AW;Franke A;Uitterlinden AG;Metspalu A;Tonjes A;Lupo A;Robino A;Johansson Å;Demirkan A;Kollerits B;Freedman BI;Ponte B;Oostra BA;Paulweber B;Krämer BK;Mitchell BD;Buckley BM;Peralta CA;Hayward C;Helmer C;Rotimi CN;Shaffer CM;Müller C;Sala C;van Duijn CM;Saint-Pierre A;Ackermann D;Shriner D;Ruggiero D;Toniolo D;Lu Y;Cusi D;Czamara D;Ellinghaus D;Siscovick DS;Ruderfer D;Gieger C;Grallert H;Rochtchina E;Atkinson EJ;Holliday EG;Boerwinkle E;Salvi E;Bottinger EP;Murgia F;Rivadeneira F;Ernst F;Kronenberg F;Hu FB;Navis GJ;Curhan GC;Ehret GB;Homuth G;Coassin S;Thun GA;Pistis G;Gambaro G;Malerba G;Montgomery GW;Eiriksdottir G;Jacobs G;Li G;Wichmann HE;Campbell H;Schmidt H;Wallaschofski H;Völzke H;Brenner H;Kroemer HK;Kramer H;Lin H;Leach IM;Ford I;Guessous I;Rudan I;Prokopenko I;Borecki I;Heid IM;Kolcic I;Persico I;Jukema JW;Wilson JF;Felix JF;Divers J;Lambert JC;Stafford JM;Gaspoz JM;Smith JA;Faul JD;Wang JJ;Ding J;Hirschhorn JN;Attia J;Whitfield JB;Chalmers J;Viikari J;Coresh J;Denny JC;Karjalainen J;Fernandes JK;Endlich K;Butterbach K;Keene KL;Lohman K;Portas L;Launer LJ;Lyytikäinen LP;Yengo L;Franke L;Ferrucci L;Rose LM;Kedenko L;Rao M;Struchalin M;Kleber ME;Cavalieri M;Haun M;Cornelis MC;Ciullo M;Pirastu M;de Andrade M;McEvoy MA;Woodward M;Adam M;Cocca M;Nauck M;Imboden M;Waldenberger M;Pruijm M;Metzger M;Stumvoll M;Evans MK;Sale MM;Kähönen M;Boban M;Bochud M;Rheinberger M;Verweij N;Bouatia-Naji N;Martin NG;Hastie N;Probst-Hensch N;Soranzo N;Devuyst O;Raitakari O;Gottesman O;Franco OH;Polasek O;Gasparini P;Munroe PB;Ridker PM;Mitchell P;Muntner P;Meisinger C;Smit JH;ICBP Consortium;AGEN Consortium;CARDIOGRAM;CHARGe-Heart Failure Group;ECHOGen Consortium;Kovacs P;Wild PS;Froguel P;Rettig R;Mägi R;Biffar R;Schmidt R;Middelberg RP;Carroll RJ;Penninx BW;Scott RJ;Katz R;Sedaghat S;Wild SH;Kardia SL;Ulivi S;Hwang SJ;Enroth S;Kloiber S;Trompet S;Stengel B;Hancock SJ;Turner ST;Rosas SE;Stracke S;Harris TB;Zeller T;Zemunik T;Lehtimäki T;Illig T;Aspelund T;Nikopensius T;Esko T;Tanaka T;Gyllensten U;Völker U;Emilsson V;Vitart V;Aalto V;Gudnason V;Chouraki V;Chen WM;Igl W;März W;Koenig W;Lieb W;Loos RJ;Liu Y;Snieder H;Pramstaller PP;Parsa A;O'Connell JR;Susztak K;Hamet P;Tremblay J;de Boer IH;Böger CA;Goessling W;Chasman DI;Köttgen A;Kao WH;Fox CS
通讯作者：
Fox CS