Quantitative Relationship Between Cumulative Risk Alleles Based on Genome-Wide Association Studies and Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis
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- Kodama Satoru
- Department of Laboratory Medicine and Clinical Epidemiology for Prevention of Noncommunicable Niigata University Graduate School of Medical and Dental Sciences
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- Fujihara Kazuya
- Department of Hematology, Endocrinology and Metabolism, Niigata University Faculty of Medicine
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- Ishiguro Hajime
- Department of Hematology, Endocrinology and Metabolism, Niigata University Faculty of Medicine
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- Horikawa Chika
- Department of Health and Nutrition, Faculty of Human Life Studies, University of Niigata Prefecture
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- Ohara Nobumasa
- Department of Hematology, Endocrinology and Metabolism, Niigata University Faculty of Medicine
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- Yachi Yoko
- Department of Administrative Dietetics, Faculty of Health and Nutrition, Yamanashi Gakuin University
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- Tanaka Shiro
- Department of Clinical Trial, Design & Management, Translational Research Center, Kyoto University Hospital
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- Shimano Hitoshi
- Department of Internal Medicine, University of Tsukuba Institute of Clinical Medicine
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- Kato Kiminori
- Department of Laboratory Medicine and Clinical Epidemiology for Prevention of Noncommunicable Niigata University Graduate School of Medical and Dental Sciences
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- Hanyu Osamu
- Department of Hematology, Endocrinology and Metabolism, Niigata University Faculty of Medicine
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- Sone Hirohito
- Department of Hematology, Endocrinology and Metabolism, Niigata University Faculty of Medicine
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Abstract
<p>Many epidemiological studies have assessed the genetic risk of having undiagnosed or of developing type 2 diabetes mellitus (T2DM) using several single nucleotide polymorphisms (SNPs) based on findings of genome-wide association studies (GWAS). However, the quantitative association of cumulative risk alleles (RAs) of such SNPs with T2DM risk has been unclear. The aim of this meta-analysis is to review the strength of the association between cumulative RAs and T2DM risk. Systematic literature searches were conducted for cross-sectional or longitudinal studies that examined odds ratios (ORs) for T2DM in relation to genetic profiles. Logarithm of the estimated OR (log OR) of T2DM for 1 increment in RAs carried (1-ΔRA) in each study was pooled using a random-effects model. There were 46 eligible studies that included 74,880 cases among 249,365 participants. In 32 studies with a cross-sectional design, the pooled OR for T2DM morbidity for 1-ΔRA was 1.16 (95% confidence interval [CI], 1.13–1.19). In 15 studies that had a longitudinal design, the OR for incident T2DM was 1.10 (95% CI, 1.08–1.13). There was large heterogeneity in the magnitude of log OR (P < 0.001 for both cross-sectional studies and longitudinal studies). The top 10 commonly used genes significantly explained the variance in the log OR (P = 0.04 for cross-sectional studies; P = 0.006 for longitudinal studies). The current meta-analysis indicated that carrying 1-ΔRA in T2DM-associated SNPs was associated with a modest risk of prevalent or incident T2DM, although the heterogeneity in the used genes among studies requires us to interpret the results with caution.</p>
Journal
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- Journal of Epidemiology
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Journal of Epidemiology 28 (1), 3-18, 2018
Japan Epidemiological Association