Genome-wide meta-analysis associates HLA-DQA1/DRB1 and LPA and lifestyle factors with human longevity.
Genome-wide meta-analysis associates HLA-DQA1/DRB1 and LPA and lifestyle factors with human longevity.
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DOI：
10.1038/s41467-017-00934-5
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发表时间：
2017-10-13
影响因子：
16.6
通讯作者：
Wilson JF
中科院分区：
文献类型：
--
作者：
Joshi PK;Pirastu N;Kentistou KA;Fischer K;Hofer E;Schraut KE;Clark DW;Nutile T;Barnes CLK;Timmers PRHJ;Shen X;Gandin I;McDaid AF;Hansen TF;Gordon SD;Giulianini F;Boutin TS;Abdellaoui A;Zhao W;Medina-Gomez C;Bartz TM;Trompet S;Lange LA;Raffield L;van der Spek A;Galesloot TE;Proitsi P;Yanek LR;Bielak LF;Payton A;Murgia F;Concas MP;Biino G;Tajuddin SM;Seppälä I;Amin N;Boerwinkle E;Børglum AD;Campbell A;Demerath EW;Demuth I;Faul JD;Ford I;Gialluisi A;Gögele M;Graff M;Hingorani A;Hottenga JJ;Hougaard DM;Hurme MA;Ikram MA;Jylhä M;Kuh D;Ligthart L;Lill CM;Lindenberger U;Lumley T;Mägi R;Marques-Vidal P;Medland SE;Milani L;Nagy R;Ollier WER;Peyser PA;Pramstaller PP;Ridker PM;Rivadeneira F;Ruggiero D;Saba Y;Schmidt R;Schmidt H;Slagboom PE;Smith BH;Smith JA;Sotoodehnia N;Steinhagen-Thiessen E;van Rooij FJA;Verbeek AL;Vermeulen SH;Vollenweider P;Wang Y;Werge T;Whitfield JB;Zonderman AB;Lehtimäki T;Evans MK;Pirastu M;Fuchsberger C;Bertram L;Pendleton N;Kardia SLR;Ciullo M;Becker DM;Wong A;Psaty BM;van Duijn CM;Wilson JG;Jukema JW;Kiemeney L;Uitterlinden AG;Franceschini N;North KE;Weir DR;Metspalu A;Boomsma DI;Hayward C;Chasman D;Martin NG;Sattar N;Campbell H;Esko T;Kutalik Z;Wilson JF
长寿的基因组分析提供了阐明人类衰老生物学的潜力。通过对606059名父母的全基因组关联荟萃分析，我们发现了两个与寿命相关的区域（HLA-DQA1/DRB1和LPA）。我们也验证了先前关于APOE、CHRNA3/5、CDKN2A/B、SH2B3和FOXO3A影响寿命的建议。接下来，我们表明戒烟、受教育程度、对新体验的开放程度和高密度脂蛋白（HDL）胆固醇水平与寿命呈正相关，而冠状动脉疾病（CAD）易感性、每天吸烟、肺癌、胰岛素抵抗和体脂的负相关程度最大。我们认为教育对寿命的影响主要是通过吸烟介导的，而肥胖的影响似乎是通过CAD起作用的。使用工具变量，我们认为身体质量指数增加一个单位会减少寿命7个月，而一年的教育会使预期寿命增加11个月。人类寿命的变化受到基因的影响。利用父母寿命的遗传数据，作者确定了HLA-DQA/DRB1和LPA的关联，并发现增加受教育程度的遗传变异对寿命有积极影响，而增加BMI对寿命有负面影响。
Genomic analysis of longevity offers the potential to illuminate the biology of human aging. Here, using genome-wide association meta-analysis of 606,059 parents’ survival, we discover two regions associated with longevity (HLA-DQA1/DRB1 and LPA). We also validate previous suggestions that APOE, CHRNA3/5, CDKN2A/B, SH2B3 and FOXO3A influence longevity. Next we show that giving up smoking, educational attainment, openness to new experience and high-density lipoprotein (HDL) cholesterol levels are most positively genetically correlated with lifespan while susceptibility to coronary artery disease (CAD), cigarettes smoked per day, lung cancer, insulin resistance and body fat are most negatively correlated. We suggest that the effect of education on lifespan is principally mediated through smoking while the effect of obesity appears to act via CAD. Using instrumental variables, we suggest that an increase of one body mass index unit reduces lifespan by 7 months while 1 year of education adds 11 months to expected lifespan. Variability in human longevity is genetically influenced. Using genetic data of parental lifespan, the authors identify associations at HLA-DQA/DRB1 and LPA and find that genetic variants that increase educational attainment have a positive effect on lifespan whereas increasing BMI negatively affects lifespan.
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影响因子：
37.8
作者：
Dehghan A;Dupuis J;Barbalic M;Bis JC;Eiriksdottir G;Lu C;Pellikka N;Wallaschofski H;Kettunen J;Henneman P;Baumert J;Strachan DP;Fuchsberger C;Vitart V;Wilson JF;Paré G;Naitza S;Rudock ME;Surakka I;de Geus EJ;Alizadeh BZ;Guralnik J;Shuldiner A;Tanaka T;Zee RY;Schnabel RB;Nambi V;Kavousi M;Ripatti S;Nauck M;Smith NL;Smith AV;Sundvall J;Scheet P;Liu Y;Ruokonen A;Rose LM;Larson MG;Hoogeveen RC;Freimer NB;Teumer A;Tracy RP;Launer LJ;Buring JE;Yamamoto JF;Folsom AR;Sijbrands EJ;Pankow J;Elliott P;Keaney JF;Sun W;Sarin AP;Fontes JD;Badola S;Astor BC;Hofman A;Pouta A;Werdan K;Greiser KH;Kuss O;Meyer zu Schwabedissen HE;Thiery J;Jamshidi Y;Nolte IM;Soranzo N;Spector TD;Völzke H;Parker AN;Aspelund T;Bates D;Young L;Tsui K;Siscovick DS;Guo X;Rotter JI;Uda M;Schlessinger D;Rudan I;Hicks AA;Penninx BW;Thorand B;Gieger C;Coresh J;Willemsen G;Harris TB;Uitterlinden AG;Järvelin MR;Rice K;Radke D;Salomaa V;Willems van Dijk K;Boerwinkle E;Vasan RS;Ferrucci L;Gibson QD;Bandinelli S;Snieder H;Boomsma DI;Xiao X;Campbell H;Hayward C;Pramstaller PP;van Duijn CM;Peltonen L;Psaty BM;Gudnason V;Ridker PM;Homuth G;Koenig W;Ballantyne CM;Witteman JC;Benjamin EJ;Perola M;Chasman DI
通讯作者：
Chasman DI
影响因子：
30.8
作者：
Barrett, Jeffrey C.;Clayton, David G.;Concannon, Patrick;Akolkar, Beena;Cooper, Jason D.;Erlich, Henry A.;Julier, Cecile;Morahan, Grant;Nerup, Jorn;Nierras, Concepcion;Plagnol, Vincent;Pociot, Flemming;Schuilenburg, Helen;Smyth, Deborah J.;Stevens, Helen;Todd, John A.;Walker, Neil M.;Rich, Stephen S.
通讯作者：
Rich, Stephen S.
影响因子：
64.8
作者：
Ehret, Georg B.;Munroe, Patricia B.;Rice, Kenneth M.;Bochud, Murielle;Johnson, Andrew D.;Chasman, Daniel I.;Smith, Albert V.;Tobin, Martin D.;Verwoert, Germaine C.;Hwang, Shih-Jen;Pihur, Vasyl;Vollenweider, Peter;O'Reilly, Paul F.;Amin, Najaf;Bragg-Gresham, Jennifer L.;Teumer, Alexander;Glazer, Nicole L.;Launer, Lenore;Zhao, Jing Hua;Aulchenko, Yurii;Heath, Simon;Sober, Siim;Parsa, Afshin;Luan, Jian'an;Arora, Pankaj;Dehghan, Abbas;Zhang, Feng;Lucas, Gavin;Hicks, Andrew A.;Jackson, Anne U.;Peden, John F.;Tanaka, Toshiko;Wild, Sarah H.;Rudan, Igor;Igl, Wilmar;Milaneschi, Yuri;Parker, Alex N.;Fava, Cristiano;Chambers, John C.;Fox, Ervin R.;Kumari, Meena;Go, Min Jin;van der Harst, Pim;Kao, Wen Hong Linda;Sjogren, Marketa;Vinay, D. G.;Alexander, Myriam;Tabara, Yasuharu;Shaw-Hawkins, Sue;Whincup, Peter H.;Liu, Yongmei;Shi, Gang;Kuusisto, Johanna;Tayo, Bamidele;Seielstad, Mark;Sim, Xueling;Khanh-Dung Hoang Nguyen;Lehtimaki, Terho;Matullo, Giuseppe;Wu, Ying;Gaunt, Tom R.;Onland-Moret, N. Charlotte;Cooper, Matthew N.;Platou, Carl G. P.;Org, Elin;Hardy, Rebecca;Dahgam, Santosh;Palmen, Jutta;Vitart, Veronique;Braund, Peter S.;Kuznetsova, Tatiana;Uiterwaal, Cuno S. P. M.;Adeyemo, Adebowale;Palmas, Walter;Campbell, Harry;Ludwig, Barbara;Tomaszewski, Maciej;Tzoulaki, Ioanna;Palmer, Nicholette D.;Aspelund, Thor;Garcia, Melissa;Chang, Yen-Pei C.;O'Connell, Jeffrey R.;Steinle, Nanette I.;Grobbee, Diederick E.;Arking, Dan E.;Kardia, Sharon L.;Morrison, Alanna C.;Hernandez, Dena;Najjar, Samer;McArdle, Wendy L.;Hadley, David;Brown, Morris J.;Connell, John M.;Hingorani, Aroon D.;Day, Ian N. M.;Lawlor, Debbie A.;Beilby, John P.;Lawrence, Robert W.;Clarke, Robert;Hopewell, Jemma C.;Ongen, Halit;Dreisbach, Albert W.;Li, Yali;Young, J. Hunter;Bis, Joshua C.;Kahonen, Mika;Viikari, Jorma;Adair, Linda S.;Lee, Nanette R.;Chen, Ming-Huei;Olden, Matthias;Pattaro, Cristian;Bolton, Judith A. Hoffman;Koettgen, Anna;Bergmann, Sven;Mooser, Vincent;Chaturvedi, Nish;Frayling, Timothy M.;Islam, Muhammad;Jafar, Tazeen H.;Erdmann, Jeanette;Kulkarni, Smita R.;Bornstein, Stefan R.;Graessler, Juergen;Groop, Leif;Voight, Benjamin F.;Kettunen, Johannes;Howard, Philip;Taylor, Andrew;Guarrera, Simonetta;Ricceri, Fulvio;Emilsson, Valur;Plump, Andrew;Barroso, Ine S.;Khaw, Kay-Tee;Weder, Alan B.;Hunt, Steven C.;Sun, Yan V.;Bergman, Richard N.;Collins, Francis S.;Bonnycastle, Lori L.;Scott, Laura J.;Stringham, Heather M.;Peltonen, Leena;Perola, Markus;Vartiainen, Erkki;Brand, Stefan-Martin;Staessen, Jan A.;Wang, Thomas J.;Burton, Paul R.;Artigas, Maria Soler;Dong, Yanbin;Snieder, Harold;Wang, Xiaoling;Zhu, Haidong;Lohman, Kurt K.;Rudock, Megan E.;Heckbert, Susan R.;Smith, Nicholas L.;Wiggins, Kerri L.;Doumatey, Ayo;Shriner, Daniel;Veldre, Gudrun;Viigimaa, Margus;Kinra, Sanjay;Prabhakaran, Dorairaj;Tripathy, Vikal;Langefeld, Carl D.;Rosengren, Annika;Thelle, Dag S.;Corsi, Anna Maria;Singleton, Andrew;Forrester, Terrence;Hilton, Gina;McKenzie, Colin A.;Salako, Tunde;Iwai, Naoharu;Kita, Yoshikuni;Ogihara, Toshio;Ohkubo, Takayoshi;Okamura, Tomonori;Ueshima, Hirotsugu;Umemura, Satoshi;Eyheramendy, Susana;Meitinger, Thomas;Wichmann, H. -Erich;Cho, Yoon Shin;Kim, Hyung-Lae;Lee, Jong-Young;Scott, James;Sehmi, Joban S.;Zhang, Weihua;Hedblad, Bo;Nilsson, Peter;Smith, George Davey;Wong, Andrew;Narisu, Narisu;Stancakova, Alena;Raffel, Leslie J.;Yao, Jie;Kathiresan, Sekar;O'Donnell, Christopher J.;Schwartz, Stephen M.;Ikram, M. Arfan;Longstreth, W. T., Jr.;Mosley, Thomas H.;Seshadri, Sudha;Shrine, Nick R. G.;Wain, Louise V.;Morken, Mario A.;Swift, Amy J.;Laitinen, Jaana;Prokopenko, Inga;Zitting, Paavo;Cooper, Jackie A.;Humphries, Steve E.;Danesh, John;Rasheed, Asif;Goel, Anuj;Hamsten, Anders;Watkins, Hugh;Bakker, Stephan J. L.;van Gilst, Wiek H.;Janipalli, Charles S.;Mani, K. Radha;Yajnik, Chittaranjan S.;Hofman, Albert;Mattace-Raso, Francesco U. S.;Oostra, Ben A.;Demirkan, Ayse;Isaacs, Aaron;Rivadeneira, Fernando;Lakatta, Edward G.;Orru, Marco;Scuteri, Angelo;Ala-Korpela, Mika;Kangas, Antti J.;Lyytikainen, Leo-Pekka;Soininen, Pasi;Tukiainen, Taru;Wurtz, Peter;Ong, Rick Twee-Hee;Doerr, Marcus;Kroemer, Heyo K.;Voelker, Uwe;Voelzke, Henry;Galan, Pilar;Hercberg, Serge;Lathrop, Mark;Zelenika, Diana;Deloukas, Panos;Mangino, Massimo;Spector, Tim D.;Zhai, Guangju;Meschia, James F.;Nalls, Michael A.;Sharma, Pankaj;Terzic, Janos;Kumar, M. V. Kranthi;Denniff, Matthew;Zukowska-Szczechowska, Ewa;Wagenknecht, Lynne E.;Fowkes, F. Gerald R.;Charchar, Fadi J.;Schwarz, Peter E. H.;Hayward, Caroline;Guo, Xiuqing;Rotimi, Charles;Bots, Michiel L.;Brand, Eva;Samani, Nilesh J.;Polasek, Ozren;Talmud, Philippa J.;Nyberg, Fredrik;Kuh, Diana;Laan, Maris;Hveem, Kristian;Palmer, Lyle J.;van der Schouw, Yvonne T.;Casas, Juan P.;Mohlke, Karen L.;Vineis, Paolo;Raitakari, Olli;Ganesh, Santhi K.;Wong, Tien Y.;Tai, E. Shyong;Cooper, Richard S.;Laakso, Markku;Rao, Dabeeru C.;Harris, Tamara B.;Morris, Richard W.;Dominiczak, Anna F.;Kivimaki, Mika;Marmot, Michael G.;Miki, Tetsuro;Saleheen, Danish;Chandak, Giriraj R.;Coresh, Josef;Navis, Gerjan;Salomaa, Veikko;Han, Bok-Ghee;Zhu, Xiaofeng;Kooner, Jaspal S.;Melander, Olle;Ridker, Paul M.;Bandinelli, Stefania;Gyllensten, Ulf B.;Wright, Alan F.;Wilson, James F.;Ferrucci, Luigi;Farrall, Martin;Tuomilehto, Jaakko;Pramstaller, Peter P.;Elosua, Roberto;Soranzo, Nicole;Sijbrands, Eric J. G.;Altshuler, David;Loos, Ruth J. F.;Shuldiner, Alan R.;Gieger, Christian;Meneton, Pierre;Uitterlinden, Andre G.;Wareham, Nicholas J.;Gudnason, Vilmundur;Rotter, Jerome I.;Rettig, Rainer;Uda, Manuela;Strachan, David P.;Witteman, Jacqueline C. M.;Hartikainen, Anna-Liisa;Beckmann, Jacques S.;Boerwinkle, Eric;Vasan, Ramachandran S.;Boehnke, Michael;Larson, Martin G.;Jarvelin, Marjo-Riitta;Psaty, Bruce M.;Abecasis, Goncalo R.;Chakravarti, Aravinda;Elliott, Paul;van Duijn, Cornelia M.;Newton-Cheh, Christopher;Levy, Daniel;Caulfield, Mark J.;Johnson, Toby
通讯作者：
Johnson, Toby
影响因子：
16.6
作者：
Joshi, Peter K.;Fischer, Krista;Wilson, James F.
通讯作者：
Wilson, James F.
影响因子：
30.8
作者：
Gudbjartsson, Daniel F.;Bjornsdottir, Unnur S.;Stefansson, Kari
通讯作者：
Stefansson, Kari