2009 Vienna - European Society of Human Genetics

Genetic analysis, linkage ans association
P17.12
Analysis of the combined discriminative value of 11 validated
obesity genetic variants
C. H. Andreasen 1 , T. Sparsø 1 , N. Grarup 1 , A. Albrechtsen 2 , K. Borch-Johnsen
3,4 , A. Sandbæk 5 , T. Lauritzen 5 , T. Jørgensen 6,7 , O. Pedersen 1,8 , T. Hansen 1,9 ;
1 Steno Diabetes Center & Hagedorn Research Institute, Gentofte, Denmark,
2 Department of Biostatistics, University of Copenhagen, Copenhagen, Denmark,
3 Steno Diabetes Center, Gentofte, Denmark, 4 Faculty of Health Science,
University of Aarhus, Aarhus, Denmark, 5 Department of General Practice, Institute
of Public Health, Aarhus University, Aarhus, Denmark, 6 Research Centre
for Prevention and Health, Glostrup University Hospital, Glostrup, Denmark,
7 Faculty of Health Science, University of Copenhagen, Copenhagen, Denmark,
8 Faculty of Health Science, University of Copenhagen, Copenhagen, Copenhagen,
Denmark, 9 Faculty of Health Sciences, University of Southern Denmark,
Denmark.
Background: Within the last years, GWA studies have identified 20
genetic variants associating with obesity or related phenotypes. The
variants are common and exhibit moderate effect sizes in the general
population. The aim of this study is to investigate the combined effect
of these variants and their ability to discriminate between normal
weight and overweight/obese individuals in a cross-sectional population
of Danes, by applying receiver operating characteristics (ROC).
Methods: 11 variants were genotyped in 3 study groups: the population-based
Inter99 study, the ADDITION Denmark screening study
cohort, and a type 2 diabetic patient group sampled at Steno Diabetes
Center. The combined study population included 5,512 normal weight,
7,458 overweight and 5,044 obese individuals. For the remaining 9
variants genotyping is still ongoing.
Results: Individual variant analyses demonstrated per allele odds ratios
for the 11 variants ranging from 1.04(0.98-1.08) to 1.21(1.14-1.27).
When combining the variants, individuals with extreme risk profile (≥15
risk alleles) showed a significant increase in risk of both overweight
1.61(1.42-1.82), p=4.1×10 -14 and obesity 1.68 (1.49-1.89), p=2.2×10 -
16 , compared to individuals with minimal risk profile (