RESEARCH ARTICLE Indications for Potential Parent-of-Origin Effects within the FTO Gene

Genome-Wide Association Studies (GWAS) were successfully applied to discover associa-tions with obesity. However, the GWAS design is usually based on unrelated individuals and inheritance information on the parental origin of the alleles is missing. Taking into ac-count parent-of-origin may provide further insights into the genetic mechanisms contributing to obesity. We hypothesized that there may be variants within the robustly replicated fat mass and obesity associated (FTO) gene that may confer different risk for obesity depend-ing on transmission from mother or father. Genome-wide genotypes and pedigree informa-tion from the Sorbs population were used. Phased genotypes among 525 individuals were generated by AlphaImpute. Subsequently, 22 SNPs within FTO introns 1 to 3 were selected and parent-of-origin specific association analyses were performed using PLINK. Interest-ingly, we identified several SNPs conferring different genetic effects (P0.05) depending on parental origin—among them, rs1861868, rs1121980 and rs9939973 (all in intron 1). To confirm our findings, we investigated the selected variants in 705 German trios comprisin