Sep 24, 2015

Variants in the FTO and CDKAL1 loci have recessive effects on risk of obesity and type 2 diabetes respectively

BioRxiv : the Preprint Server for Biology
Andrew R WoodMichael N Weedon

Abstract

Genome-wide association studies have identified hundreds of common genetic variants associated with obesity and Type 2 diabetes. These studies have focused on additive association tests. Identifying deviations from additivity may provide new biological insights and explain some of the missing heritability for these diseases. To identify non-additive associations we performed a genome-wide association study using a dominance deviation model for BMI, obesity and Type 2 diabetes (4,040 cases) in 120,286 individuals of British ancestry from the UK Biobank study. Known obesity-associated variants in FTO showed strong evidence for deviation from additivity (P=3x10-5) through a recessive effect of the BMI-increasing allele. The average BMI of individuals carrying 0, 1 or 2 BMI-raising alleles was 27.27kg/m2 (95% CI:27.22-27.31), 27.54kg/m2 (95% CI:27.50-27.58), and 28.07kg/m2 (95% CI:28.0-28.14), respectively. A similar effect was observed in 105,643 individuals from the GIANT consortium (P=0.003; Pmeta-analysis=1x10-7). We also detected a recessive effect (Pdomdev=5x10-4) at CDKAL1 for Type 2 diabetes risk. Homozygous risk allele carriers had an OR=1.48 (95% CI:1.32-1.65) in comparison to the heterozygous group that had an OR=1.06 (9...Continue Reading

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Mentioned in this Paper

CDKAL1 gene
Genome-Wide Association Study
Diabetes Mellitus, Non-Insulin-Dependent
Study
Genome
Obesity
FTO
FTO gene
Widespread
CDKAL1

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