Association of genetic predisposition to obesity with type 2 diabetes risk in Han Chinese individuals
Association of genetic predisposition to obesity with type 2 diabetes risk in Han Chinese individuals
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中国汉族人群肥胖遗传倾向与 2 型糖尿病风险的关系
DOI：
10.1007/s00125-014-3308-7
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发表时间：
2014-06
期刊：
影响因子：
8.2
通讯作者：
X.
中科院分区：
文献类型：
--
作者：
Li;H.;Lin;X.
目的/假设肥胖是2型糖尿病的主要危险因素，但对东亚人群中bmi相关基因座对2型糖尿病风险的贡献知之甚少。方法在本研究中，对1873例2型糖尿病患者和1839例对照汉族人群的30种已知bmi相关变异和遗传风险评分（GRS）进行检测，以确定这些变异的bmi增加等位基因与2型糖尿病和相关血糖特征的相关性。在有或没有调整BMI的加性模型下，分别进行Logistic和线性回归分析，以确定与2型糖尿病风险或相关血糖特征的关联。结果总体人群中，GRS与BMI升高呈显著相关（β [SE] 0.070 [0.016];p= 1.33 × 10−5）。在不调整BMI的情况下，GRS中每增加一个增加BMI的等位基因，使2型糖尿病的风险增加1.029倍（95% CI 1.008, 1.050;p= 0.0056），调整BMI后，这种关联略有减弱（OR 1.022; 95% CI 1.002, 1.043;p= 0.035）。在非糖尿病对照组中，GRS也与BMI调整后的β细胞功能HOMA （HOMA- b）相关（β [SE]−0.876 [0.345];p= 0.011）。值得注意的是，经HOMA-B校正后，GRS与2型糖尿病的相关性被消除（OR 1.012; 95% CI 0.986, 1.039;p= 0.380）。结论/解释：我们的研究结果表明，肥胖的遗传易感性会导致2型糖尿病的风险增加，与BMI无关，部分原因是β细胞功能受损。
Aims/hypothesisObesity is a major risk factor for type 2 diabetes, but little is known about the contribution of BMI-associated loci to type 2 diabetes risk in East Asian populations.MethodsIn this study, 30 known BMI-associated variants and a genetic risk score (GRS) calculated by summing the BMI-increasing alleles of these variants were tested for associations with type 2 diabetes and related glycaemic traits in 1,873 cases of type 2 diabetes and 1,839 controls in Han Chinese individuals. Logistic and linear regression analyses were performed to determine the association with type 2 diabetes risk or related glycaemic traits, respectively, under an additive model with or without adjustment for BMI.ResultsThe GRS was significantly associated with increased BMI (β [SE] 0.070 [0.016];p= 1.33 × 10−5) in the overall population. Each additional BMI-increasing allele in the GRS increased type 2 diabetes risk by 1.029-fold (95% CI 1.008, 1.050;p= 0.0056) without adjustment for BMI, and the association was slightly attenuated after adjustment for BMI (OR 1.022; 95% CI 1.002, 1.043;p= 0.035). In non-diabetic controls, the GRS was also associated with HOMA of beta cell function (HOMA-B) with adjustment for BMI (β [SE] −0.876 [0.345];p= 0.011). Notably, the association of GRS with type 2 diabetes was abolished after adjusting for HOMA-B (OR 1.012; 95% CI 0.986, 1.039;p= 0.380).Conclusions/interpretationOur results suggested that genetic predisposition to obesity leads to increased risk of type 2 diabetes, independent of BMI and partly through impaired beta cell function.
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全基因组关联研究确定 GRK5 和 RASGRP1 为中国汉族 2 型糖尿病基因座
影响因子：
7.7
作者：
Li H;Gan W;Lu L;Dong X;Han X;Hu C;Yang Z;Sun L;Bao W;Li P;He M;Sun L;Wang Y;Zhu J;Ning Q;Tang Y;Zhang R;Wen J;Wang D;Zhu X;Guo K;Zuo X;Guo X;Yang H;Zhou X;DIAGRAM Consortium;AGEN-T2D Consortium;Zhang X;Qi L;Loos RJ;Hu FB;Wu T;Liu Y;Liu L;Yang Z;Hu R;Jia W;Ji L;Li Y;Lin X
通讯作者：
Lin X
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：
16.2
作者：
Meier JJ;Bonadonna RC
通讯作者：
Bonadonna RC
影响因子：
30.8
作者：
Okada, Yukinori;Kubo, Michiaki;Ohmiya, Hiroko;Takahashi, Atsushi;Kumasaka, Natsuhiko;Hosono, Naoya;Maeda, Shiro;Wen, Wanqing;Dorajoo, Rajkumar;Go, Min Jin;Zheng, Wei;Kato, Norihiro;Wu, Jer-Yuarn;Lu, Qi;Tsunoda, Tatsuhiko;Yamamoto, Kazuhiko;Nakamura, Yusuke;Kamatani, Naoyuki;Tanaka, Toshihiro
通讯作者：
Tanaka, Toshihiro
影响因子：
4.9
作者：
Robiou-du-Pont, S.;Bonnefond, A.;Meyre, D.
通讯作者：
Meyre, D.