Combined analyses of 20 common obesity susceptibility variants.

  1. Camilla Helene Sandholt (cila{at}novonordisk.com)a,b,
  2. Thomas Sparsøa,
  3. Niels Grarupa,
  4. Anders Albrechtsenc,
  5. Katrine Almindb,
  6. Lars Hansend,
  7. Ulla Tofte,
  8. Torben Jørgensene,f,
  9. Torben Hansena,g and
  10. Oluf Pedersena,h,i
  1. aHagedorn Research Institute, Gentofte, Denmark
  2. bNovo Nordisk A/S, Medical and Science, Development Projects, Bagsværd, Denmark
  3. cDepartment of Biostatistics, University of Copenhagen, Copenhagen, Denmark
  4. dBristol-Meyers Squibb & Co., Discovery Medicine and Clinical Pharmacology, CV Metabolic Diseases, Princeton NJ, USA
  5. eResearch Centre for Prevention and Health, Glostrup University Hospital, Glostrup, Denmark
  6. fFaculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
  7. gFaculty of Health Sciences, University of Southern Denmark, Odense, Denmark
  8. hFaculty of Health Science, University of Aarhus, Aarhus, Denmark
  9. iInstitute of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark

Abstract

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 individually they exhibit small-to-modest effect sizes.

Research Design and Methods: Here 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 OR of 2.00 [1.47-2.72], p=4.0×10−5, and obese, with an OR of 2.62 [1.76-3.92], p=6.4×10−7, compared to the 10% of the study participants who carried less than 14 risk-alleles. Discrimination ability for overweight and obesity, using the 20 SNPs, was determined to AUCs of 0.53 and 0.58, respectively. When combining SNP data with conventional non-genetic 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 non-genetic factors alone (AUC=0.67).

Conclusion: 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 non-genetic risk factors.

Footnotes

    • Received July 16, 2009.
    • Accepted January 20, 2010.