Meta-analytic research on the relationship between cumulative risk alleles and risk of type 2 diabetes mellitus.
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 (RAtotal ) 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 RAtotal (ΔRAtotal ) 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 ΔRAtotal 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 ΔRAtotal were almost identical.


CONCLUSIONS
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.
Department of Laboratory Medicine and Clinical Epidemiology for Prevention of Noncommunicable Diseases, Niigata University Faculty of Medicine, Niigata, Japan.
Satoru
S
Kodama
Department of Internal Medicine, University of Tsukuba Institute of Clinical Medicine, Ibaraki, Japan.
Kazuya
K
Fujihara
Department of Hematology, Endocrinology and Metabolism, Niigata University Faculty of Medicine, Niigata, Japan.
Hajime
H
Ishiguro
Department of Health and Nutrition, Faculty of Human Life Studies, University of Niigata Prefecture, Niigata, Japan.
Chika
C
Horikawa
Department of Laboratory Medicine and Clinical Epidemiology for Prevention of Noncommunicable Diseases, Niigata University Faculty of Medicine, Niigata, Japan.|Department of Hematology, Endocrinology and Metabolism, Niigata University Faculty of Medicine, Niigata, Japan.
Nobumasa
N
Ohara
Department of Administrative Dietetics, Faculty of Health and Nutrition, Yamanashi Gakuin University, Yamanashi, Japan.
Yoko
Y
Yachi
Department of Clinical Trial, Design and Management, Translational Research Center, Kyoto University Hospital, Kyoto, Japan.
Shiro
S
Tanaka
Department of Internal Medicine, University of Tsukuba Institute of Clinical Medicine, Ibaraki, Japan.
Hitoshi
H
Shimano
Department of Laboratory Medicine and Clinical Epidemiology for Prevention of Noncommunicable Diseases, Niigata University Faculty of Medicine, Niigata, Japan.
Kiminori
K
Kato
Department of Hematology, Endocrinology and Metabolism, Niigata University Faculty of Medicine, Niigata, Japan.
Osamu
O
Hanyu
Department of Hematology, Endocrinology and Metabolism, Niigata University Faculty of Medicine, Niigata, Japan.
Hirohito
H
Sone
D015415:Biomarkers / Q000032:analysis*; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors
D015415:Biomarkers
correlation study; genetic polymorphisms; genetic susceptibility; meta-analysis as topic; type 2 diabetes mellitus