Indications for potential parent-of-origin effects within the FTO gene

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 fu...

Full description

Saved in:

Bibliographic Details
Published in:	PloS one 2015-03, Vol.10 (3), p.e0119206-e0119206
Main Authors:	Liu, Xuanshi, Hinney, Anke, Scholz, Markus, Scherag, André, Tönjes, Anke, Stumvoll, Michael, Stadler, Peter F, Hebebrand, Johannes, Böttcher, Yvonne
Format:	Article
Language:	eng
Subjects:	Adolescent obesity Adult Alleles Alpha-Ketoglutarate-Dependent Dioxygenase FTO Analysis Bioinformatics Body fat Body Mass Index Child & adolescent psychiatry Childhood obesity Comorbidity Epidemiology Family Family studies Female Fto gene Genes Genetic effects Genetic Predisposition to Disease Genome-wide association studies Genome-Wide Association Study Genomes Genomics Genotype Genotypes Germany Heredity Humans Introns Linkage Disequilibrium Male Middle Aged Obesity Obesity - epidemiology Obesity - genetics Obesity in adolescence Obesity in children Parents Pedigree Polymorphism, Single Nucleotide Population Proteins - genetics Psychotherapy Single nucleotide polymorphisms Single-nucleotide polymorphism Studies
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	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.
ISSN:	1932-6203 1932-6203