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Meta‐analytic research on the relationship between cumulative risk alleles and risk of type 2 diabetes mellitus
Author(s) -
Kodama Satoru,
Fujihara Kazuya,
Ishiguro Hajime,
Horikawa Chika,
Ohara Nobumasa,
Yachi Yoko,
Tanaka Shiro,
Shimano Hitoshi,
Kato Kiminori,
Hanyu Osamu,
Sone Hirohito
Publication year - 2016
Publication title -
diabetes/metabolism research and reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.307
H-Index - 110
eISSN - 1520-7560
pISSN - 1520-7552
DOI - 10.1002/dmrr.2680
Subject(s) - odds ratio , confounding , medicine , type 2 diabetes mellitus , meta analysis , demography , confidence interval , body mass index , diabetes mellitus , endocrinology , sociology
Background Our aim is to examine the dose–response association between cumulative genetic risk and actual risk of type 2 diabetes mellitus (T2DM) and the influence of adjustment for covariates on T2DM risk through a comprehensive meta‐analysis of observational studies. Methods Electronic literature search using EMBASE and MEDLINE (from 2003 to 2014) was conducted for cross‐sectional or longitudinal studies that presented the odds ratio (OR) for T2DM in each group with categories based on the total number of risk alleles (RAs) carried (RA total ) using at least two single‐nucleotide polymorphisms. Spline regression model was used to determine the shape of the relationship between the difference from the referent group of each study in RA total ( Δ RA total ) and the natural logarithms of ORs (log OR) for T2DM. Results Sixty‐five eligible studies that included 68 267 cases among 182 603 participants were analysed. In both crude and adjusted ORs, defined by adjusting the risk for at least two confounders among age, gender and body mass index, the slope of the log OR for T2DM became less steep as the Δ RA total increased. In the analysis limited to 14 cross‐sectional and four longitudinal studies presenting both crude and adjusted ORs, regression curves of both ORs in relation to Δ RA total were almost identical. Conclusion Using only single‐nucleotide polymorphisms for T2DM screening was of limited value. However, when genotypic T2DM risk was considered independently from risk in relation to covariates, it was suggested that genetic profiles might have a supplementary role related to conventional T2DM risk factors in identifying individuals at high risk of T2DM. Copyright © 2015 John Wiley & Sons, Ltd.