A Genome-Wide Association Study Identifies <i>GRK5</i> and <i>RASGRP1</i> as Type 2 Diabetes Loci in Chinese Hans

Li, Huaixing; Gan, Wei; Lu, Ling; Dong, Xiao; Han, Xueyao; Hu, Cheng; Yang, Zhen; Sun, Liang; Bao, Wei; Li, Pengtao; He, Meian; Sun, Liangdan; Wang, Yiqin; Zhu, Jingwen; Ning, Qianqian; Tang, Yong; Zhang, Rong; Wen, Jie; Wang, Di; Zhu, Xilin; Guo, Kunquan; Zuo, Xianbo; X, Guo; Yang, Handong; Zhou, Xianghai; Zhang, Xuejun; Qi, Lü; Loos, Ruth J.F.; Hu, Frank B.; Wu, Tangchun; Liu, Ying; Liu, Liegang; Yang, Ze; Hu, Renming; Jia, Weiping; Ji, Linong; Li, Yixue; Lin, Xu

doi:10.2337/db12-0454

Cited by 162 publications

(131 citation statements)

References 49 publications

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“…Full details of study populations, design, protocols and biochemical measurements have been described previously [6]. BMI was calculated as weight/height 2 (kg/m 2 ).…”

Section: Methodsmentioning

confidence: 99%

Association of genetic predisposition to obesity with type 2 diabetes risk in Han Chinese individuals

Zhu

Zong

et al. 2014

Diabetologia

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Aims/hypothesis Obesity is a major risk factor for type 2 diabetes, but little is known about the contribution of BMIassociated loci to type 2 diabetes risk in East Asian populations. Methods In this study, 30 known BMI-associated variants and a genetic risk score (GRS) calculated by summing the BMIincreasing 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. ) 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/interpretation Our 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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“…Full details of study populations, design, protocols and biochemical measurements have been described previously [6]. BMI was calculated as weight/height 2 (kg/m 2 ).…”

Section: Methodsmentioning

confidence: 99%

Association of genetic predisposition to obesity with type 2 diabetes risk in Han Chinese individuals

Zhu

Zong

et al. 2014

Diabetologia

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“…[35][36][37][38][39][40][41][42][43][44][45][46][47]. The majority of SNPs that associated with T2D in one ethnic group showed some evidence of association in other ethnic groups as well.…”

Section: Gwas Imputation and Meta-analysis In Diverse Ethnic Groupsmentioning

confidence: 94%

Complex Genetics of Type 2 Diabetes and Effect Size: What have We Learned from Isolated Populations?

Nair

Baier

2015

Rev Diabet Stud

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■ AbstractGenetic studies in large outbred populations have documented a complex, highly polygenic basis for type 2 diabetes (T2D). Most of the variants currently known to be associated with T2D risk have been identified in large studies that included tens of thousands of individuals who are representative of a single major ethnic group such as European, Asian, or African. However, most of these variants have only modest effects on the risk for T2D; identification of definitive 'causal variant' or 'causative loci' is typically lacking. Studies in isolated populations offer several advantages over outbred populations despite being, on average, much smaller in sample size. For example, reduced genetic variability, enrichment of rare variants, and a more uniform environment and lifestyle, which are hallmarks of isolated populations, can reduce the complexity of identifying disease-associated genes. To date, studies in isolated populations have provided valuable insight into the genetic basis of T2D by providing both a deeper understanding of previously identified T2D-associated variants (e.g. demonstrating that variants in KCNQ1 have a strong parent-of-origin effect) or providing novel variants (e.g. ABCC8 in Pima Indians, TBC1D4 in the Greenlandic population, HNF1A in Canadian Oji-Cree). This review summarizes advancements in genetic studies of T2D in outbred and isolated populations, and provides information on whether the difference in the prevalence of T2D in different populations (Pima Indians vs. non-Hispanic Whites and non-Hispanic Whites vs. non-Hispanic Blacks) can be explained by the difference in risk allele frequencies of established T2D variants.

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“…In addition, two other GLIS3 variants, rs7041847 and rs10814916, were reported to confer the susceptibility to T2D in East Asians (Cho et al 2012, Sakai et al 2013 and in Chinese (Li et al 2013), respectively. In contrast to GLIS3 rs7034200, a risk SNP for T2D in multi-ethnic populations, GLIS3 rs7041847, appears to confer T2D susceptibility only in East Asians.…”

Section: Glis3 and Type 2 Diabetesmentioning

confidence: 99%

Emerging roles of GLIS3 in neonatal diabetes, type 1 and type 2 diabetes

Wen

Yang

2017

Journal of Molecular Endocrinology

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GLI-similar 3 (GLIS3), a member of the Krüppel-like zinc finger protein subfamily, is predominantly expressed in the pancreas, thyroid and kidney. Glis3 mRNA can be initially detected in mouse pancreas at embryonic day 11.5 and is largely restricted to β cells, pancreatic polypeptide-expressing cells, as well as ductal cells at later stage of pancreas development. Mutations in GLIS3 cause a neonatal diabetes syndrome, characterized by neonatal diabetes, congenital hypothyroidism and polycystic kidney.

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A Genome-Wide Association Study Identifies GRK5 and RASGRP1 as Type 2 Diabetes Loci in Chinese Hans

Cited by 162 publications

References 49 publications

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

Complex Genetics of Type 2 Diabetes and Effect Size: What have We Learned from Isolated Populations?

Emerging roles of GLIS3 in neonatal diabetes, type 1 and type 2 diabetes

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