Insights into the genetic basis of type 2 diabetes.
Insights into the genetic basis of type 2 diabetes.
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DOI：
10.1111/jdi.12067
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发表时间：
2013-05-06
影响因子：
3.2
通讯作者：
Kato N
中科院分区：
文献类型：
--
作者：
Kato N
2型糖尿病是最常见的复杂疾病之一，已经做出相当大的努力来阐明其病理生理机制。最近，大规模的全基因组关联（GWA）研究通过以无偏、无假设的方式在整个基因组中搜索易感性变体，成功地鉴定了与2型糖尿病密切相关的遗传位点。基因座的数量从2006年的3个上升到今天的70个左右。对于常见的2型糖尿病相关变异，注意到三个特征。首先，个体变异的遗传影响通常是适度的;大多数情况下，等位基因比值比在1.06和1.20之间。第二，大多数的基因座确定的日期是不明显的候选基因或附近，但有些往往位于基因间区域。第三，虽然基因座的数量有限，但2型糖尿病相关性可能存在一定的人群特异性。虽然我们可以通过参考体外实验的数据来估计GWA研究中检测到的单个基因座的单个或几个靶基因，但这些靶基因的相当大一部分的生物学功能仍然是未知的。然而，新的生物学是从GWA研究发现中产生的;例如，涉及β细胞功能障碍的基因在2型糖尿病相关区域中过度表达。对于翻译的进步，我们刚刚开始面临新的挑战-阐明多方面的（即，分子、细胞和生理学）机制的见解疾病生物学通过考虑与环境的相互作用。本文综述了2型糖尿病遗传学的最新进展及其现实潜力。
Type 2 diabetes is one of the most common complex diseases, of which considerable efforts have been made to unravel the pathophysiological mechanisms. Recently, large‐scale genome‐wide association (GWA) studies have successfully identified genetic loci robustly associated with type 2 diabetes by searching susceptibility variants across the entire genome in an unbiased, hypothesis‐free manner. The number of loci has climbed from just three in 2006 to approximately 70 today. For the common type 2 diabetes‐associated variants, three features have been noted. First, genetic impacts of individual variants are generally modest; mostly, allelic odds ratios range between 1.06 and 1.20. Second, most of the loci identified to date are not in or near obvious candidate genes, but some are often located in the intergenic regions. Third, although the number of loci is limited, there might be some population specificity in type 2 diabetes association. Although we can estimate a single or a few target genes for individual loci detected in GWA studies by referring to the data for experiments in vitro, biological function remains largely unknown for a substantial part of such target genes. Nevertheless, new biology is arising from GWA study discoveries; for example, genes implicated in β‐cell dysfunction are over‐represented within type 2 diabetes‐associated regions. Toward translational advances, we have just begun to face new challenges – elucidation of multifaceted (i.e., molecular, cellular and physiological) mechanistic insights into disease biology by considering interaction with the environment. The present review summarizes recent advances in the genetics of type 2 diabetes, together with its realistic potential.
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全基因组关联研究的荟萃分析确定了东亚人 2 型糖尿病的 8 个新位点
影响因子：
30.8
作者：
Cho, Yoon Shin;Chen, Chien-Hsiun;Hu, Cheng;Long, Jirong;Ong, Rick Twee Hee;Sim, Xueling;Takeuchi, Fumihiko;Wu, Ying;Go, Min Jin;Yamauchi, Toshimasa;Chang, Yi-Cheng;Kwak, Soo Heon;Ma, Ronald C. W.;Yamamoto, Ken;Adair, Linda S.;Aung, Tin;Cai, Qiuyin;Chang, Li-Ching;Chen, Yuan-Tsong;Gao, Yutang;Hu, Frank B.;Kim, Hyung-Lae;Kim, Sangsoo;Kim, Young Jin;Lee, Jeannette Jen-Mai;Lee, Nanette R.;Li, Yun;Liu, Jian Jun;Lu, Wei;Nakamura, Jiro;Nakashima, Eitaro;Ng, Daniel Peng-Keat;Tay, Wan Ting;Tsai, Fuu-Jen;Wong, Tien Yin;Yokota, Mitsuhiro;Zheng, Wei;Zhang, Rong;Wang, Congrong;So, Wing Yee;Ohnaka, Keizo;Ikegami, Hiroshi;Hara, Kazuo;Cho, Young Min;Cho, Nam H.;Chang, Tien-Jyun;Bao, Yuqian;Hedman, Asa K.;Morris, Andrew P.;McCarthy, Mark I.;Takayanagi, Ryoichi;Park, Kyong Soo;Jia, Weiping;Chuang, Lee-Ming;Chan, Juliana C. N.;Maeda, Shiro;Kadowaki, Takashi;Lee, Jong-Young;Wu, Jer-Yuarn;Teo, Yik Ying;Tai, E. Shyong;Shu, Xiao Ou;Mohlke, Karen L.;Kato, Norihiro;Han, Bok-Ghee;Seielstad, Mark
通讯作者：
Seielstad, Mark
影响因子：
16.2
作者：
de Miguel-Yanes JM;Shrader P;Pencina MJ;Fox CS;Manning AK;Grant RW;Dupuis J;Florez JC;D'Agostino RB Sr;Cupples LA;Meigs JB;MAGIC Investigators;DIAGRAM+ Investigators
通讯作者：
DIAGRAM+ Investigators
DOI：
10.1126/science.1183621
发表时间：
2010-04-09
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Kasowski M;Grubert F;Heffelfinger C;Hariharan M;Asabere A;Waszak SM;Habegger L;Rozowsky J;Shi M;Urban AE;Hong MY;Karczewski KJ;Huber W;Weissman SM;Gerstein MB;Korbel JO;Snyder M
通讯作者：
Snyder M
影响因子：
7.7
作者：
Gloyn, AL;Weedon, MN;Frayling, TM
通讯作者：
Frayling, TM
影响因子：
158.5
作者：
Florez, Jose C.;Jablonski, Kathleen A.;Altshuler, David
通讯作者：
Altshuler, David