Genomics and phenomics of body mass index reveals a complex disease network.
Genomics and phenomics of body mass index reveals a complex disease network.
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DOI：
10.1038/s41467-022-35553-2
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发表时间：
2022-12-29
影响因子：
16.6
通讯作者：
O'Donnell, Christopher J.
中科院分区：
文献类型：
--
作者：
Huang, Jie;Huffman, Jennifer E.;Huang, Yunfeng;Do Valle, Italo;Assimes, Themistocles L.;Raghavan, Sridharan;Voight, Benjamin F.;Liu, Chang;Barabasi, Albert-Laszlo;Huang, Rose D. L.;Hui, Qin;Nguyen, Xuan-Mai T.;Ho, Yuk-Lam;Djousse, Luc;Lynch, Julie A.;Vujkovic, Marijana;Tcheandjieu, Catherine;Tang, Hua;Damrauer, Scott M.;Reaven, Peter D.;Miller, Donald;Phillips, Lawrence S.;Ng, Maggie C. Y.;Graff, Mariaelisa;Haiman, Christopher A.;Loos, Ruth J. F.;North, Kari E.;Yengo, Loic;Smith, George Davey;Saleheen, Danish;Gaziano, J. Michael;Rader, Daniel J.;Tsao, Philip S.;Cho, Kelly;Chang, Kyong-Mi;Wilson, Peter W. F.;Sun, Yan, V;O'Donnell, Christopher J.
身体质量指数（BMI）升高是可遗传的，与许多影响发病率和死亡率的健康状况有关。在广泛的常见疾病条件下研究BMI的遗传关联提供了扩展当前关于肥胖相关疾病的广度和深度的知识的机会。我们在欧洲（N~ 110万）和非洲（N~ 10万）血统的参与者中分别确定了906个（364个新的）和41个（6个新的）全基因组BMI显著位点。使用包括2446种变异的BMI遗传风险评分，在百万退伍军人计划中有316种诊断相关，其中96.5%显示风险增加。共病网络分析揭示了7个疾病社区，其中包含与BMI相关的多种相互关联的疾病以及社区之间的广泛联系。孟德尔随机化分析证实了广泛的器官系统中的许多表型，包括循环系统（心力衰竭，缺血性心脏病，心房颤动），泌尿生殖系统（慢性肾衰竭），呼吸系统（呼吸衰竭，哮喘），肌肉骨骼和皮肤系统的疾病，这些疾病在疾病群体内部和之间相互联系。这项工作表明，BMI的复杂遗传结构与广泛的主要健康状况有关，支持了预防和治疗肥胖的综合方法的必要性。体重指数升高是可遗传的，与许多影响发病率和死亡率的健康状况有关。在这里，作者确定了超过900个身体质量指数（BMI）的遗传位点，并发现了300多个与BMI增加相关的诊断。
Elevated body mass index (BMI) is heritable and associated with many health conditions that impact morbidity and mortality. The study of the genetic association of BMI across a broad range of common disease conditions offers the opportunity to extend current knowledge regarding the breadth and depth of adiposity-related diseases. We identify 906 (364 novel) and 41 (6 novel) genome-wide significant loci for BMI among participants of European (N~1.1 million) and African (N~100,000) ancestry, respectively. Using a BMI genetic risk score including 2446 variants, 316 diagnoses are associated in the Million Veteran Program, with 96.5% showing increased risk. A co-morbidity network analysis reveals seven disease communities containing multiple interconnected diseases associated with BMI as well as extensive connections across communities. Mendelian randomization analysis confirms numerous phenotypes across a breadth of organ systems, including conditions of the circulatory (heart failure, ischemic heart disease, atrial fibrillation), genitourinary (chronic renal failure), respiratory (respiratory failure, asthma), musculoskeletal and dermatologic systems that are deeply interconnected within and across the disease communities. This work shows that the complex genetic architecture of BMI associates with a broad range of major health conditions, supporting the need for comprehensive approaches to prevent and treat obesity. Elevated body mass index is heritable and associated with many health conditions that impact morbidity and mortality. Here, the authors identify greater than 900 genetic loci for body mass index (BMI) and find over 300 diagnoses associated with increasing BMI.
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影响因子：
46.9
作者：
通讯作者：
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影响因子：
30.8
作者：
Monda, Keri L.;Chen, Gary K.;Taylor, Kira C.;Palmer, Cameron;Edwards, Todd L.;Lange, Leslie A.;Ng, Maggie C. Y.;Adeyemo, Adebowale A.;Allison, Matthew A.;Bielak, Lawrence F.;Chen, Guanjie;Graff, Mariaelisa;Irvin, Marguerite R.;Rhie, Suhn K.;Li, Guo;Liu, Yongmei;Liu, Youfang;Lu, Yingchang;Nalls, Michael A.;Sun, Yan V.;Wojczynski, Mary K.;Yanek, Lisa R.;Aldrich, Melinda C.;Ademola, Adeyinka;Amos, Christopher I.;Bandera, Elisa V.;Bock, Cathryn H.;Britton, Angela;Broeckel, Ulrich;Cai, Quiyin;Caporaso, Neil E.;Carlson, Chris S.;Carpten, John;Casey, Graham;Chen, Wei-Min;Chen, Fang;Chen, Yii-Der I.;Chiang, Charleston W. K.;Coetzee, Gerhard A.;Demerath, Ellen;Deming-Halverson, Sandra L.;Driver, Ryan W.;Dubbert, Patricia;Feitosa, Mary F.;Feng, Ye;Freedman, Barry I.;Gillanders, Elizabeth M.;Gottesman, Omri;Guo, Xiuqing;Haritunians, Talin;Harris, Tamara;Harris, Curtis C.;Hennis, Anselm J. M.;Hernandez, Dena G.;McNeill, Lorna H.;Howard, Timothy D.;Howard, Barbara V.;Howard, Virginia J.;Johnson, Karen C.;Kang, Sun J.;Keating, Brendan J.;Kolb, Suzanne;Kuller, Lewis H.;Kutlar, Abdullah;Langefeld, Carl D.;Lettre, Guillaume;Lohman, Kurt;Lotay, Vaneet;Lyon, Helen;Manson, Joann E.;Maixner, William;Meng, Yan A.;Monroe, Kristine R.;Morhason-Bello, Imran;Murphy, Adam B.;Mychaleckyj, Josyf C.;Nadukuru, Rajiv;Nathanson, Katherine L.;Nayak, Uma;N'Diaye, Amidou;Nemesure, Barbara;Wu, Suh-Yuh;Leske, M. Cristina;Neslund-Dudas, Christine;Neuhouser, Marian;Nyante, Sarah;Ochs-Balcom, Heather;Ogunniyi, Adesola;Ogundiran, Temidayo O.;Ojengbede, Oladosu;Olopade, Olufunmilayo I.;Palmer, Julie R.;Ruiz-Narvaez, Edward A.;Palmer, Nicholette D.;Press, Michael F.;Rampersaud, Evandine;Rasmussen-Torvik, Laura J.;Rodriguez-Gil, Jorge L.;Salako, Babatunde;Schadt, Eric E.;Schwartz, Ann G.;Shriner, Daniel A.;Siscovick, David;Smith, Shad B.;Wassertheil-Smoller, Sylvia;Speliotes, Elizabeth K.;Spitz, Margaret R.;Sucheston, Lara;Taylor, Herman;Tayo, Bamidele O.;Tucker, Margaret A.;Van Den Berg, David J.;Edwards, Digna R. Velez;Wang, Zhaoming;Wiencke, John K.;Winkler, Thomas W.;Witte, John S.;Wrensch, Margaret;Wu, Xifeng;Yang, James J.;Levin, Albert M.;Young, Taylor R.;Zakai, Neil A.;Cushman, Mary;Zanetti, Krista A.;Zhao, Jing Hua;Zhao, Wei;Zheng, Yonglan;Zhou, Jie;Ziegler, Regina G.;Zmuda, Joseph M.;Fernandes, Jyotika K.;Gilkeson, Gary S.;Kamen, Diane L.;Hunt, Kelly J.;Spruill, Ida J.;Ambrosone, Christine B.;Ambs, Stefan;Arnett, Donna K.;Atwood, Larry;Becker, Diane M.;Berndt, Sonja I.;Bernstein, Leslie;Blot, William J.;Borecki, Ingrid B.;Bottinger, Erwin P.;Bowden, Donald W.;Burke, Gregory;Chanock, Stephen J.;Cooper, Richard S.;Ding, Jingzhong;Duggan, David;Evans, Michele K.;Fox, Caroline;Garvey, W. Timothy;Bradfield, Jonathan P.;Hakonarson, Hakon;Grant, Struan F. A.;Hsing, Ann;Chu, Lisa;Hu, Jennifer J.;Huo, Dezheng;Ingles, Sue A.;John, Esther M.;Jordan, Joanne M.;Kabagambe, Edmond K.;Kardia, Sharon L. R.;Kittles, Rick A.;Goodman, Phyllis J.;Klein, Eric A.;Kolonel, Laurence N.;Le Marchand, Loic;Liu, Simin;McKnight, Barbara;Millikan, Robert C.;Mosley, Thomas H.;Padhukasahasram, Badri;Williams, L. Keoki;Patel, Sanjay R.;Peters, Ulrike;Pettaway, Curtis A.;Peyser, Patricia A.;Psaty, Bruce M.;Redline, Susan;Rotimi, Charles N.;Rybicki, Benjamin A.;Sale, Michele M.;Schreiner, Pamela J.;Signorello, Lisa B.;Singleton, Andrew B.;Stanford, Janet L.;Strom, Sara S.;Thun, Michael J.;Vitolins, Mara;Zheng, Wei;Moore, Jason H.;Williams, Scott M.;Ketkar, Shamika;Zhu, Xiaofeng;Zonderman, Alan B.;Kooperberg, Charles;Papanicolaou, George J.;Henderson, Brian E.;Reiner, Alex P.;Hirschhorn, Joel N.;Loos, Ruth J. F.;North, Kari E.;Haiman, Christopher A.
通讯作者：
Haiman, Christopher A.
影响因子：
37.8
作者：
Dale CE;Fatemifar G;Palmer TM;White J;Prieto-Merino D;Zabaneh D;Engmann JEL;Shah T;Wong A;Warren HR;McLachlan S;Trompet S;Moldovan M;Morris RW;Sofat R;Kumari M;Hyppönen E;Jefferis BJ;Gaunt TR;Ben-Shlomo Y;Zhou A;Gentry-Maharaj A;Ryan A;UCLEB Consortium; METASTROKE Consortium;Mutsert R;Noordam R;Caulfield MJ;Jukema JW;Worrall BB;Munroe PB;Menon U;Power C;Kuh D;Lawlor DA;Humphries SE;Mook-Kanamori DO;Sattar N;Kivimaki M;Price JF;Davey Smith G;Dudbridge F;Hingorani AD;Holmes MV;Casas JP
通讯作者：
Casas JP
影响因子：
5.7
作者：
Breland, Jessica Y.;Phibbs, Ciaran S.;Frayne, SusanM.
通讯作者：
Frayne, SusanM.
影响因子：
3.8
作者：
de Goede, Barry;Timmermans, Lucas;Jeekel, Johannes
通讯作者：
Jeekel, Johannes