title: Indications for potential parent-of-origin effects within the FTO gene.
abstract: Genome-Wide Association Studies (GWAS) were successfully applied to discover associations 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 account 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 depending on transmission from mother or father. Genome-wide genotypes and pedigree information 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. Interestingly, we identified several SNPs conferring different genetic effects (P≤0.05) 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 comprising an (extremely) obese child or adolescent and both parents. Again, we observed evidence for POE effects in intron 2 and 3 (P≤0.05) as indicated by the parental asymmetry test. Our results suggest that the obesity risk transmitted by several FTO variants may depend on the parental origin of the allele. Larger family-based studies are warranted to replicate our findings.
authors: IFB Adiposity Diseases, University of Leipzig, Leipzig, Germany; Bioinformatics Group, Department of Computer Science, University of Leipzig, Leipzig, Germany.
authors: Xuanshi
authors: X
authors: Liu
authors: Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy Universitätsklinikum Essen, University of Duisburg-Essen, Essen, Germany.
authors: Anke
authors: A
authors: Hinney
authors: Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.
authors: Markus
authors: M
authors: Scholz
authors: Clinical Epidemiology, Integrated Research and Treatment Center (IFB) Center for Sepsis Control and Care (CSCC), Jena University Hospital, Jena, Germany.
authors: André
authors: A
authors: Scherag
authors: Department of Medicine, University of Leipzig, Leipzig, Germany.
authors: Anke
authors: A
authors: Tönjes
authors: IFB Adiposity Diseases, University of Leipzig, Leipzig, Germany; Department of Medicine, University of Leipzig, Leipzig, Germany.
authors: Michael
authors: M
authors: Stumvoll
authors: Fraunhofer Institute for Cell Therapy and Immunology, AG RNomics, Leipzig, Germany; Interdisciplinary Center of Bioinformatics, University of Leipzig, Leipzig, Germany; Institute for Theoretical Chemistry, University of Vienna, Vienna, Austria; Sante Fe Institute, Santa Fe, New Mexico, United States of America.
authors: Peter F
authors: PF
authors: Stadler
authors: Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy Universitätsklinikum Essen, University of Duisburg-Essen, Essen, Germany.
authors: Johannes
authors: J
authors: Hebebrand
authors: IFB Adiposity Diseases, University of Leipzig, Leipzig, Germany.
authors: Yvonne
authors: Y
authors: Böttcher
mesh_terms: D000328:Adult; D000483:Alleles; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D015992:Body Mass Index; D015897:Comorbidity; D005190:Family; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D005858:Germany; D006801:Humans; D007438:Introns; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000453:epidemiology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics*
chemical_list: D011506:Proteins; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human