Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Liu, Xuanshi, Hinney, Anke, Scholz, Markus, Scherag, André, Tönjes, Anke, Stumvoll, Michael, Stadler, Peter F., Hebebrand, Johannes, Böttcher, Yvonne
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4368796/
https://www.ncbi.nlm.nih.gov/pubmed/25793382
http://dx.doi.org/10.1371/journal.pone.0119206
_version_ 1782362689419345920
author Liu, Xuanshi
Hinney, Anke
Scholz, Markus
Scherag, André
Tönjes, Anke
Stumvoll, Michael
Stadler, Peter F.
Hebebrand, Johannes
Böttcher, Yvonne
author_facet Liu, Xuanshi
Hinney, Anke
Scholz, Markus
Scherag, André
Tönjes, Anke
Stumvoll, Michael
Stadler, Peter F.
Hebebrand, Johannes
Böttcher, Yvonne
author_sort Liu, Xuanshi
collection PubMed
description 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.
format Online
Article
Text
id pubmed-4368796
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-43687962015-03-27 Indications for Potential Parent-of-Origin Effects within the FTO Gene Liu, Xuanshi Hinney, Anke Scholz, Markus Scherag, André Tönjes, Anke Stumvoll, Michael Stadler, Peter F. Hebebrand, Johannes Böttcher, Yvonne PLoS One Research Article 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. Public Library of Science 2015-03-20 /pmc/articles/PMC4368796/ /pubmed/25793382 http://dx.doi.org/10.1371/journal.pone.0119206 Text en © 2015 Liu et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Liu, Xuanshi
Hinney, Anke
Scholz, Markus
Scherag, André
Tönjes, Anke
Stumvoll, Michael
Stadler, Peter F.
Hebebrand, Johannes
Böttcher, Yvonne
Indications for Potential Parent-of-Origin Effects within the FTO Gene
title Indications for Potential Parent-of-Origin Effects within the FTO Gene
title_full Indications for Potential Parent-of-Origin Effects within the FTO Gene
title_fullStr Indications for Potential Parent-of-Origin Effects within the FTO Gene
title_full_unstemmed Indications for Potential Parent-of-Origin Effects within the FTO Gene
title_short Indications for Potential Parent-of-Origin Effects within the FTO Gene
title_sort indications for potential parent-of-origin effects within the fto gene
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4368796/
https://www.ncbi.nlm.nih.gov/pubmed/25793382
http://dx.doi.org/10.1371/journal.pone.0119206
work_keys_str_mv AT liuxuanshi indicationsforpotentialparentoforigineffectswithintheftogene
AT hinneyanke indicationsforpotentialparentoforigineffectswithintheftogene
AT scholzmarkus indicationsforpotentialparentoforigineffectswithintheftogene
AT scheragandre indicationsforpotentialparentoforigineffectswithintheftogene
AT tonjesanke indicationsforpotentialparentoforigineffectswithintheftogene
AT stumvollmichael indicationsforpotentialparentoforigineffectswithintheftogene
AT stadlerpeterf indicationsforpotentialparentoforigineffectswithintheftogene
AT hebebrandjohannes indicationsforpotentialparentoforigineffectswithintheftogene
AT bottcheryvonne indicationsforpotentialparentoforigineffectswithintheftogene