期刊
DIABETES
卷 59, 期 7, 页码 1667-1673出版社
AMER DIABETES ASSOC
DOI: 10.2337/db09-1042
关键词
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资金
- Lundbeck Foundation Centre for Applied Medical Genomics in Personalized Disease Prediction, Prevention and Care (LuCAMP)
- Danish Health Research Council
- FOOD Study Group/the Danish Ministry of Food
- Agriculture and Fisheries and the Ministry of Family and Consumer Affairs [2101-05-0044]
- Novo Nordisk A/S Research & Development Corporate Research Affairs
- Danish Ministry of Science Technology and Innovation
- Faculty of Health Sciences of Aarhus University
- Danish Clinical Intervention Research Academy
- Danish Diabetes Association
- European Commission [LSHM-CT-2005-018734]
- Danish Obesity Research Center (DanORC)
- Danish Council for Strategic Research [2101-06-0005]
- Danish Research Counsil
- Danish Centre for Health Technology Assessment
- Novo Nordisk
- Research Foundation of Copenhagen County
- Ministry of Internal Affaires and Health
- Danish Heart Foundation
- Danish Pharmaceutical Association
- Augustinus Foundation
- Ib Henriksen Foundation
- Becket Foundation
OBJECTIVE-Genome-wide association studies and linkage studies have identified 20 validated genetic variants associated with obesity and/or related phenotypes. The variants are common, and they individually exhibit small-to-modest effect sizes. RESEARCH DESIGN AND METHODS-In this study we investigate the combined effect of these variants and their ability to discriminate between normal weight and overweight/obese individuals. We applied receiver operating characteristics (ROC) curves, and estimated the area under the ROC curve (AUC) as a measure of the discriminatory ability. The analyses were performed cross-sectionally in the population-based Inter99 cohort: where 1,725 normal weight, 1,519 overweight, and 681 obese individuals were successfully genotyped for all 20 variants. RESULTS-When combining all variants, the 10% of the study participants who carried more than 22 risk-alleles showed a significant increase in probability of being both overweight with an odds ratio of 2.00 (1.47-2.72), P = 4.0 x 10(-5), and obese with an OR of 2.62 (1.76-3.92), P = 6.4 x 10(-7), compared with the 10% of the study participants who carried less than 14 risk-alleles. Discrimination ability for overweight and obesity, using the 20 single nucleotide polymorphisms (SNPs), was determined to AUCs of 0.53 and 0.58, respectively. When combining SNP data with conventional nongenetic risk factors of obesity, the discrimination ability increased to 0.64 for overweight and 0.69 for obesity. The latter is significantly higher (P < 0.001) than for the nongenetic factors alone (AUG = 0.67). CONCLUSIONS-The discriminative value of the 20 validated common obesity variants is at present time sparse and too weak for clinical utility, however, they add to increase the discrimination ability of conventional nongenetic risk factors. Diabetes 59:1667-1673, 2010
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