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Cross-sectional and longitudinal replication analyses of genome-wide association loci of type 2 diabetes in Han Chinese.

ABSTRACT: This study aimed to examine genomic loci of type 2 diabetes (T2D) initially identified by genome-wide association studies in populations of European ancestry for their associations with T2D and quantitative glycemic traits, as well as their effects on longitudinal change in fasting plasma glucose (FPG) and T2D development, in the Chinese population. Single nucleotide polymorphisms (SNP) from 25 loci were genotyped in a large case-control sample of 10,001 subjects (5,338 T2D cases and 4,663 controls) and a prospective cohort of 1,881 Chinese. In the case-control sample, 8 SNPs in or near WFS1, CDKAL1, CDKN2A/2B, CDC123, HHEX, TCF7L2, KCNQ1, and MTNR1B were significantly associated with T2D (P<0.05). Thirteen SNPs were associated with quantitative glycemic traits. For example, the most significant SNP, rs10811661 near CDKN2A/2B (P?=?1.11×10(-8) for T2D), was also associated with 2-h glucose level of an oral glucose tolerance test (P?=?9.11×10(-3)) and insulinogenic index (P?=?2.71×10(-2)). In the cohort study, individuals carrying more risk alleles of the replicated SNPs had greater FPG increase and T2D incidence in a 7.5-year follow-up period, with each quartile increase in the number of risk alleles being associated with a 0.06 mmol/l greater increase in FPG (P?=?0.03) and 19% higher odds of developing T2D (P?=?0.058). Our study identified the associations of several established T2D-loci in Europeans with T2D and quantitative glycemic traits in the Chinese population. The prospective data also suggest their potential role in the risk prediction of T2D in the Chinese population.

SUBMITTER: Zhao Q

PROVIDER: S-EPMC3956742 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Cross-sectional and longitudinal replication analyses of genome-wide association loci of type 2 diabetes in Han Chinese.

Zhao Qi Q Xiao Jianzhong J He Jiang J Zhang Xuelian X Hong Jing J Kong Xiaomu X Mills Katherine T KT Weng Jianping J Jia Weiping W Yang Wenying W

PloS one 20140317 3

This study aimed to examine genomic loci of type 2 diabetes (T2D) initially identified by genome-wide association studies in populations of European ancestry for their associations with T2D and quantitative glycemic traits, as well as their effects on longitudinal change in fasting plasma glucose (FPG) and T2D development, in the Chinese population. Single nucleotide polymorphisms (SNP) from 25 loci were genotyped in a large case-control sample of 10,001 subjects (5,338 T2D cases and 4,663 contr ...[more]

PMID: 24637646

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Project description:BackgroundCluster headache is a highly debilitating neurological disorder with considerable inter-ethnic differences. Genome-wide association studies (GWAS) recently identified replicable genomic loci for cluster headache in Europeans, but the genetic underpinnings for cluster headache in Asians remain unclear. The objective of this study is to investigate the genetic architecture and susceptibility loci of cluster headache in Han Chinese resided in Taiwan.MethodsWe conducted a two-stage genome-wide association study in a Taiwanese cohort enrolled from 2007 through 2022 to identify the genetic variants associated with cluster headache. Diagnosis of cluster headache was retrospectively ascertained with the criteria of International Classification of Headache Disorders, third edition. Control subjects were enrolled from the Taiwan Biobank. Genotyping was conducted with the Axiom Genome-Wide Array TWB chip, followed by whole genome imputation. A polygenic risk score was developed to differentiate patients from controls. Downstream analyses including gene-set and tissue enrichment, linkage disequilibrium score regression, and pathway analyses were performed.ResultsWe enrolled 734 patients with cluster headache and 9,846 population-based controls. We identified three replicable loci, with the lead SNPs being rs1556780 in CAPN2 (odds ratio = 1.59, 95% CI 1.42‒1.78, p = 7.61 × 10-16), rs10188640 in MERTK (odds ratio = 1.52, 95% CI 1.33‒1.73, p = 8.58 × 10-13), and rs13028839 in STAB2 (odds ratio = 0.63, 95% CI 0.52‒0.78, p = 2.81 × 10-8), with the latter two replicating the findings in European populations. Several previously reported genes also showed significant associations with cluster headache in our samples. Polygenic risk score differentiated patients from controls with an area under the receiver operating characteristic curve of 0.77. Downstream analyses implicated circadian regulation and immunological processes in the pathogenesis of cluster headache.ConclusionsThis study revealed the genetic architecture and novel susceptible loci of cluster headache in Han Chinese residing in Taiwan. Our findings support the common genetic contributions of cluster headache across ethnicities and provide novel mechanistic insights into the pathogenesis of cluster headache.

Dataset Information

Cross-sectional and longitudinal replication analyses of genome-wide association loci of type 2 diabetes in Han Chinese.

Publications

Cross-sectional and longitudinal replication analyses of genome-wide association loci of type 2 diabetes in Han Chinese.

Similar Datasets

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