Quantitative Relationship Between Cumulative Risk Alleles Based on Genome-Wide Association Studies and Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis 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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Author(s)

    • Kodama Satoru
    • Department of Laboratory Medicine and Clinical Epidemiology for Prevention of Noncommunicable Niigata University Graduate School of Medical and Dental Sciences
    • Hanyu Osamu
    • Department of Hematology, Endocrinology and Metabolism, Niigata University Faculty of Medicine
    • Sone Hirohito
    • Department of Hematology, Endocrinology and Metabolism, Niigata University Faculty of Medicine
    • Fujihara Kazuya
    • Department of Hematology, Endocrinology and Metabolism, Niigata University Faculty of Medicine
    • Ishiguro Hajime
    • Department of Hematology, Endocrinology and Metabolism, Niigata University Faculty of Medicine
    • Horikawa Chika
    • Department of Health and Nutrition, Faculty of Human Life Studies, University of Niigata Prefecture
    • Ohara Nobumasa
    • Department of Hematology, Endocrinology and Metabolism, Niigata University Faculty of Medicine
    • Yachi Yoko
    • Department of Administrative Dietetics, Faculty of Health and Nutrition, Yamanashi Gakuin University
    • Tanaka Shiro
    • Department of Clinical Trial, Design & Management, Translational Research Center, Kyoto University Hospital
    • Shimano Hitoshi
    • Department of Internal Medicine, University of Tsukuba Institute of Clinical Medicine
    • Kato Kiminori
    • Department of Laboratory Medicine and Clinical Epidemiology for Prevention of Noncommunicable Niigata University Graduate School of Medical and Dental Sciences

Abstract

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>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 (<i>P</i> < 0.001 for both cross-sectional studies and longitudinal studies). The top 10 commonly used genes significantly explained the variance in the log OR (<i>P</i> = 0.04 for cross-sectional studies; <i>P</i> = 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

  • Journal of Epidemiology

    Journal of Epidemiology 28(1), 3-18, 2018

    Japan Epidemiological Association

Codes

  • NII Article ID (NAID)
    130006301960
  • NII NACSIS-CAT ID (NCID)
    AA10952696
  • Text Lang
    ENG
  • Article Type
    journal article
  • ISSN
    0917-5040
  • Data Source
    IR  J-STAGE 
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