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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DOI：
10.2188/jea.je20160151
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发表时间：
2018-01-05
影响因子：
4.7
通讯作者：
Sone H
中科院分区：
文献类型：
--
作者：
Kodama S;Fujihara K;Ishiguro H;Horikawa C;Ohara N;Yachi Y;Tanaka S;Shimano H;Kato K;Hanyu O;Sone H
许多流行病学研究已经基于全基因组关联研究（GWAS）的发现，使用几种单核苷酸多态性（SNP）来评估患有未诊断或发展为2型糖尿病（T2 DM）的遗传风险。然而，这种SNP的累积风险等位基因（RA）与T2 DM风险的定量关联尚不清楚。本荟萃分析的目的是审查累积RA与T2 DM风险之间的关联强度。对横断面或纵向研究进行了系统性文献检索，这些研究检查了T2 DM与遗传特征相关的比值比（OR）。使用随机效应模型汇总每项研究中携带RA（1-ΔRA）1个增量的T2 DM估计OR（log OR）的对数。共有46项合格研究，包括249，365名参与者中的74，880例病例。在32项采用横断面设计的研究中，1-ΔRA的T2 DM发病率合并OR为1.16（95%置信区间[CI]，1.13-1.19）。在15项纵向设计的研究中，T2 DM事件的OR为1.10（95% CI，1.08-1.13）。log OR的大小存在很大的异质性（横断面研究和纵向研究均P < 0.001）。前10个常用基因显著解释了log OR的方差（横断面研究P = 0.04;纵向研究P = 0.006）。目前的荟萃分析表明，在T2 DM相关SNP中携带1-ΔRA与流行或偶发T2 DM的适度风险相关，尽管研究中所用基因的异质性要求我们谨慎解释结果。
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.