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  • 标题:Quantitative Relationship Between Cumulative Risk Alleles Based on Genome-Wide Association Studies and Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis
  • 本地全文:下载
  • 作者:Satoru Kodama ; Kazuya Fujihara ; Hajime Ishiguro
  • 期刊名称:Journal of Epidemiology
  • 印刷版ISSN:0917-5040
  • 电子版ISSN:1349-9092
  • 出版年度:2018
  • 卷号:28
  • 期号:1
  • 页码:3-18
  • DOI:10.2188/jea.JE20160151
  • 语种:English
  • 出版社:Japan Epidemiological Association
  • 摘要:

    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.

  • 关键词:genome-wide association studies;risk allele;type 2 diabetes mellitus;meta-analysis
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