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

• Published in: Journal of epidemiology 2018-01, Vol.28 (1), p.3-18
• Main Authors: Kodama, Satoru, Fujihara, Kazuya, Ishiguro, Hajime, Horikawa, Chika, Ohara, Nobumasa, Yachi, Yoko, Tanaka, Shiro, Shimano, Hitoshi, Kato, Kiminori, Hanyu, Osamu, Sone, Hirohito
• Format: Article
• Language: English
• Subjects: Alleles; Clinical Epidemiology; Confidence intervals; Correlation analysis; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Epidemiology; Genes; Genome-wide association studies; Genomes; Heterogeneity; Literature reviews; Longitudinal studies; Meta-analysis; Morbidity; Review; risk allele; Single-nucleotide polymorphism; Systematic review; type 2 diabetes mellitus
• ISSN: 0917-5040; 1349-9092
• DOI: 10.2188/jea.JE20160151

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.