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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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2015
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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 |
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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 |
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