Genome-wide association study of height-adjusted BMI in childhood identifies functional variant in ADCY3.
Bottom Line: SNPs in ADCY3 (adenylate cyclase 3) were associated at genome-wide significance level (rs11676272 (0.28 kg/m(3.1) change per allele G (0.19, 0.38), P = 6 × 10(-9) ).The association signal at ADCY3 appeared to be driven by a missense variant and it was strongly correlated with expression of this gene.Our work highlights the importance of well understood phenotype use (and the danger of convention) in characterising genetic contributions to complex traits.
Affiliation: MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK.Show MeSH
Mentions: For variation at SNPs across the ADCY3 locus and conventional BMI there was not genome-wide significant evidence for association (Figure 2b) [rs11676272 (0.25 kg/m2 (0.15, 0.35), P = 6 × 10−7)]. zBMI (BMI standardised for age) was not associated with rs11676272 [0.022 change in zBMI per allele G (−0.01 to 0.06), P = 0.224)]. In contrast, the association of rs1558902 in FTO remained genome-wide significant [0.33 kg/m2 (0.23, 0.43), P = 1 × 10−10]. Evidence for association at the ADCY3 locus and rs11676272 [0.28 kg/m2 (0.19, 0.38), P = 6 × 10−9] remained genome-wide significant, as expected, when performing a GWAS on conventional BMI adjusted for height (Figure 2c). Furthermore, in sensitivity analyses performing regional single marker association analyses with BMI adjusted for height conditional on rs11676272 dose, all evidence for association across the ADCY3 region was lost (Figure 3).
Affiliation: MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK.