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Meta-analysis of genome-wide association studies identifies eight new loci for type 2 diabetes in east Asians
Authors: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
Institution:Center for Genome Science, National Institute of Health, Osong Health Technology Administration Complex, Chungcheongbuk-do, Cheongwon-gun, Gangoe-myeon, Yeonje-ri, Korea. yooncho33@korea.kr
Abstract:We conducted a three-stage genetic study to identify susceptibility loci for type 2 diabetes (T2D) in east Asian populations. We followed our stage 1 meta-analysis of eight T2D genome-wide association studies (6,952 cases with T2D and 11,865 controls) with a stage 2 in silico replication analysis (5,843 cases and 4,574 controls) and a stage 3 de novo replication analysis (12,284 cases and 13,172 controls). The combined analysis identified eight new T2D loci reaching genome-wide significance, which mapped in or near GLIS3, PEPD, FITM2-R3HDML-HNF4A, KCNK16, MAEA, GCC1-PAX4, PSMD6 and ZFAND3. GLIS3, which is involved in pancreatic beta cell development and insulin gene expression, is known for its association with fasting glucose levels. The evidence of an association with T2D for PEPD and HNF4A has been shown in previous studies. KCNK16 may regulate glucose-dependent insulin secretion in the pancreas. These findings, derived from an east Asian population, provide new perspectives on the etiology of T2D.
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