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PMID: 19966805 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

Nature genetics ·Vol. 42 ·No. 1 ·2010-01-00 ·Pages 68-71

Wallace C, Smyth DJ, Maisuria-Armer M, Walker NM, Todd JA, Clayton DG

Abstract

Genome-wide association (GWA) studies to map common disease susceptibility loci have been hugely successful, with over 300 reproducibly associated loci reported to date. However, these studies have not yet provided convincing evidence for any susceptibility locus subject to parent-of-origin effects. Using imputation to extend existing GWA datasets, we have obtained robust evidence at rs941576 for paternally inherited risk of type 1 diabetes (T1D; ratio of allelic effects for paternal versus maternal transmissions = 0.75; 95% confidence interval (CI) = 0.71-0.79). This marker is in the imprinted region of chromosome 14q32.2, which contains the functional candidate gene DLK1. Our meta-analysis also provided support at genome-wide significance for a T1D locus at chromosome 19p13.2. The highest association was at marker rs2304256 (odds ratio (OR) = 0.86; 95%CI = 0.82-0.90) in the TYK2 gene, which has previously been associated with systemic lupus erythematosus and multiple sclerosis.

MeSH Terms
Calcium-Binding Proteins Chromosomes, Human, Pair 14/genetics Diabetes Mellitus, Type 1/genetics Family Health Female Genetic Predisposition to Disease Genome-Wide Association Study Genomic Imprinting Genotype Humans Intercellular Signaling Peptides and Proteins/genetics Linkage Disequilibrium Male Membrane Proteins/genetics Meta-Analysis as Topic Polymorphism, Single Nucleotide Proteins/genetics RNA, Long Noncoding
Chemicals
Calcium-Binding Proteins DLK1 protein, human Intercellular Signaling Peptides and Proteins MEG3 non-coding RNA, human Membrane Proteins Proteins RNA, Long Noncoding
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Wallace Chris
Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.
Smyth Deborah J
Maisuria-Armer Meeta
Walker Neil M
Todd John A
Clayton David G
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Article Info
Journal
Nature genetics
Abbr.
Nat Genet
ISSN
1546-1718
DOI
10.1038/ng.493
Published
2010-01-00
Epub
2009-00-06
Pages
68-71
Language
English
Region
United States
NLM ID
9216904
PMCID
PMC2820243
Subset
IM
Grants
Medical Research Council · G0000934 · United Kingdom
NIMH NIH HHS · MH059571 · United States
Wellcome Trust · 068545/Z/02 · United Kingdom
NIMH NIH HHS · MH067257 · United States
Wellcome Trust · 089989 · United Kingdom
Wellcome Trust · 076113 · United Kingdom
NIMH NIH HHS · R01 MH067257 · United States
NIMH NIH HHS · MH63420 · United States
NIMH NIH HHS · MH060879 · United States
NIMH NIH HHS · MH059588 · United States
Wellcome Trust · 076113/C/04/Z · United Kingdom
NIMH NIH HHS · R01 MH059566 · United States
NIMH NIH HHS · MH59566 · United States
Wellcome Trust · 061858 · United Kingdom
Medical Research Council · grant G0000934 · United Kingdom
NIMH NIH HHS · R01 MH060879 · United States
NIMH NIH HHS · MH59587 · United States
NIMH NIH HHS · R01 MH061675 · United States
NIMH NIH HHS · MH061675 · United States
Wellcome Trust · 079895 · United Kingdom
NIMH NIH HHS · MH60870 · United States
NIMH NIH HHS · MH59586 · United States
NIMH NIH HHS · R01 MH060870 · United States
NIDDK NIH HHS · U01 DK062418 · United States
NIMH NIH HHS · R01 MH059571 · United States
NIMH NIH HHS · R01 MH059565 · United States
NIMH NIH HHS · R01 MH059587 · United States
PHS HHS · U01 · United States
NIMH NIH HHS · MH059565 · United States
NIMH NIH HHS · R01 MH059586 · United States
NIMH NIH HHS · R01 MH063420 · United States
NIMH NIH HHS · R01 MH059588 · United States
External Links
PubMed source DOI: 10.1038/ng.493 PMC Full Text View journal details
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