The imprinted DLK1-MEG3 gene region on chromosome 14q32.2 alters susceptibility to type 1 diabetes

Genomewide association studies to map common disease susceptibility loci have been hugely successful with over 300 reproducibly associated loci reported to date,1 but, perhaps surprisingly, have not yet provided convincing evidence for any susceptibility locus subject to parent of origin effects. We...

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Autores principales: Wallace, Chris, Smyth, Deborah J, Maisuria-Armer, Meeta, Walker, Neil M, Todd, John A, Clayton, David G
Formato: Texto
Lenguaje:English
Publicado: 2009
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2820243/
https://www.ncbi.nlm.nih.gov/pubmed/19966805
http://dx.doi.org/10.1038/ng.493
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author Wallace, Chris
Smyth, Deborah J
Maisuria-Armer, Meeta
Walker, Neil M
Todd, John A
Clayton, David G
author_facet Wallace, Chris
Smyth, Deborah J
Maisuria-Armer, Meeta
Walker, Neil M
Todd, John A
Clayton, David G
author_sort Wallace, Chris
collection PubMed
description Genomewide association studies to map common disease susceptibility loci have been hugely successful with over 300 reproducibly associated loci reported to date,1 but, perhaps surprisingly, have not yet provided convincing evidence for any susceptibility locus subject to parent of origin effects. We used imputation to extend existing genomewide association datasets2, 3, 4 and here report robust evidence, at rs941576, for paternally inherited risk of type 1 diabetes (T1D, ratio of allelic effects for paternal vs maternal transmissions = 0.75, 95%CI=0.71–0.79), in the imprinted region of chromosome 14q32.2, which contains a functional candidate gene, DLK1. Our meta-analysis also provided support at genomewide significance for a T1D locus at chromosome 19p13.2, with the highest association at marker rs2304256 (OR=0.86, 95%CI=0.82–0.90) in the TYK2 gene, which has previously associated with systemic lupus erythematosus.5
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spelling pubmed-28202432010-07-01 The imprinted DLK1-MEG3 gene region on chromosome 14q32.2 alters susceptibility to type 1 diabetes Wallace, Chris Smyth, Deborah J Maisuria-Armer, Meeta Walker, Neil M Todd, John A Clayton, David G Nat Genet Article Genomewide association studies to map common disease susceptibility loci have been hugely successful with over 300 reproducibly associated loci reported to date,1 but, perhaps surprisingly, have not yet provided convincing evidence for any susceptibility locus subject to parent of origin effects. We used imputation to extend existing genomewide association datasets2, 3, 4 and here report robust evidence, at rs941576, for paternally inherited risk of type 1 diabetes (T1D, ratio of allelic effects for paternal vs maternal transmissions = 0.75, 95%CI=0.71–0.79), in the imprinted region of chromosome 14q32.2, which contains a functional candidate gene, DLK1. Our meta-analysis also provided support at genomewide significance for a T1D locus at chromosome 19p13.2, with the highest association at marker rs2304256 (OR=0.86, 95%CI=0.82–0.90) in the TYK2 gene, which has previously associated with systemic lupus erythematosus.5 2009-12-06 2010-01 /pmc/articles/PMC2820243/ /pubmed/19966805 http://dx.doi.org/10.1038/ng.493 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Wallace, Chris
Smyth, Deborah J
Maisuria-Armer, Meeta
Walker, Neil M
Todd, John A
Clayton, David G
The imprinted DLK1-MEG3 gene region on chromosome 14q32.2 alters susceptibility to type 1 diabetes
title The imprinted DLK1-MEG3 gene region on chromosome 14q32.2 alters susceptibility to type 1 diabetes
title_full The imprinted DLK1-MEG3 gene region on chromosome 14q32.2 alters susceptibility to type 1 diabetes
title_fullStr The imprinted DLK1-MEG3 gene region on chromosome 14q32.2 alters susceptibility to type 1 diabetes
title_full_unstemmed The imprinted DLK1-MEG3 gene region on chromosome 14q32.2 alters susceptibility to type 1 diabetes
title_short The imprinted DLK1-MEG3 gene region on chromosome 14q32.2 alters susceptibility to type 1 diabetes
title_sort imprinted dlk1-meg3 gene region on chromosome 14q32.2 alters susceptibility to type 1 diabetes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2820243/
https://www.ncbi.nlm.nih.gov/pubmed/19966805
http://dx.doi.org/10.1038/ng.493
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