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Genomics. 2019 Jan;111(1):34-42. doi: 10.1016/j.ygeno.2017.12.010. Epub 2017 Dec 19.

Two novel susceptibility loci for type 2 diabetes mellitus identified by longitudinal exome-wide association studies in a Japanese population.

Author information

1
Department of Human Functional Genomics, Advanced Science Research Promotion Center, Mie University, Tsu 514-8507, Japan; CREST, Japan Science and Technology Agency, Kawaguchi 332-0012, Japan. Electronic address: hyasukou@proof.ocn.ne.jp.
2
CREST, Japan Science and Technology Agency, Kawaguchi 332-0012, Japan; Computer Science Department, College of Information Science, University of Tsukuba, Tsukuba 305-8573, Japan; RIKEN Center for Advanced Intelligence Project, Tokyo 103-0027, Japan.
3
CREST, Japan Science and Technology Agency, Kawaguchi 332-0012, Japan; RIKEN Center for Advanced Intelligence Project, Tokyo 103-0027, Japan; Department of Computer Science, Nagoya Institute of Technology, Nagoya 466-8555, Japan.
4
Department of Human Functional Genomics, Advanced Science Research Promotion Center, Mie University, Tsu 514-8507, Japan; Department of Internal Medicine, Meitoh Hospital, Nagoya 465-0025, Japan.
5
Department of Human Functional Genomics, Advanced Science Research Promotion Center, Mie University, Tsu 514-8507, Japan; Department of Cardiology, Kasugai Municipal Hospital, Kasugai 486-8510, Japan.
6
Department of Cardiovascular Medicine, Inabe General Hospital, Inabe 511-0428, Japan.
7
Department of Cardiovascular Medicine, Gifu Prefectural Tajimi Hospital, Tajimi 507-8522, Japan.
8
Department of Human Functional Genomics, Advanced Science Research Promotion Center, Mie University, Tsu 514-8507, Japan; CREST, Japan Science and Technology Agency, Kawaguchi 332-0012, Japan.

Abstract

Recent genome-wide association studies identified genetic variants that confer susceptibility to type 2 diabetes mellitus (T2DM). However, few longitudinal genome-wide association studies of this metabolic disorder have been reported to date. Therefore, we performed a longitudinal exome-wide association study of T2DM, using 24,579 single nucleotide polymorphisms (SNPs) and repeated measurements from 6022 Japanese individuals. The generalized estimating equation model was applied to test relations of SNPs to three T2DM-related parameters: prevalence of T2DM, fasting plasma glucose level, and blood glycosylated hemoglobin content. Three SNPs that passed quality control were significantly (P<2.26×10-7) associated with two of the three T2DM-related parameters in additive and recessive models. Of the three SNPs, rs6414624 in EVC and rs78338345 in GGA3 were novel susceptibility loci for T2DM. In the present study, the SNP of GGA3 was predicted to be a genetic variant whose minor allele frequency has recently increased in East Asia.

KEYWORDS:

Blood glycosylated hemoglobin; Exome-wide association study; Fasting plasma glucose; Generalized estimating equation; Longitudinal data; Type 2 diabetes mellitus

PMID:
29273463
DOI:
10.1016/j.ygeno.2017.12.010
[Indexed for MEDLINE]
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