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Statistical colocalization of genetic risk variants for related autoimmune diseases in the context of common controls.

Fortune, Mary D; Guo, Hui; Burren, Oliver; Schofield, Ellen; Walker, Neil M; Ban, Maria; Sawcer, Stephen J; Bowes, John; Worthington, Jane; Barton, Anne; Eyre, Steve; Todd, John A; Wallace, Chris

Nature genetics. 2015;47(7):839-46.

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Abstract

Determining whether potential causal variants for related diseases are shared can identify overlapping etiologies of multifactorial disorders. Colocalization methods disentangle shared and distinct causal variants. However, existing approaches require independent data sets. Here we extend two colocalization methods to allow for the shared-control design commonly used in comparison of genome-wide association study results across diseases. Our analysis of four autoimmune diseases-type 1 diabetes (T1D), rheumatoid arthritis, celiac disease and multiple sclerosis-identified 90 regions that were associated with at least one disease, 33 (37%) of which were associated with 2 or more disorders. Nevertheless, for 14 of these 33 shared regions, there was evidence that the causal variants differed. We identified new disease associations in 11 regions previously associated with one or more of the other 3 disorders. Four of eight T1D-specific regions contained known type 2 diabetes (T2D) candidate genes (COBL, GLIS3, RNLS and BCAR1), suggesting a shared cellular etiology.

Bibliographic metadata

Type of resource:
Content type:
Publication status:
Accepted
Publication type:
Publication form:
Published date:
Language:
eng
Journal title:
Abbreviated journal title:
ISSN:
Place of publication:
United States
Volume:
47
Issue:
7
Pagination:
839-46
Digital Object Identifier:
10.1038/ng.3330
Pubmed Identifier:
26053495
Pii Identifier:
ng.3330
Attached files embargo period:
Immediate release
Attached files release date:
29th June, 2015
Access state:
Active

Institutional metadata

Academic department(s):

Record metadata

Manchester eScholar ID:
uk-ac-man-scw:267503
Created by:
Ingram, Mary
Created:
29th June, 2015, 10:02:09
Last modified by:
Ingram, Mary
Last modified:
12th December, 2015, 08:14:46

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