학술논문
Pervasive sharing of genetic effects in autoimmune disease.
Document Type
article
Author
Chris Cotsapas; Benjamin F Voight; Elizabeth Rossin; Kasper Lage; Benjamin M Neale; Chris Wallace; Gonçalo R Abecasis; Jeffrey C Barrett; Timothy Behrens; Judy Cho; Philip L De Jager; James T Elder; Robert R Graham; Peter Gregersen; Lars Klareskog; Katherine A Siminovitch; David A van Heel; Cisca Wijmenga; Jane Worthington; John A Todd; David A Hafler; Stephen S Rich; Mark J Daly; FOCiS Network of Consortia
Source
PLoS Genetics, Vol 7, Iss 8, p e1002254 (2011)
Subject
Language
English
ISSN
1553-7390
1553-7404
1553-7404
Abstract
Genome-wide association (GWA) studies have identified numerous, replicable, genetic associations between common single nucleotide polymorphisms (SNPs) and risk of common autoimmune and inflammatory (immune-mediated) diseases, some of which are shared between two diseases. Along with epidemiological and clinical evidence, this suggests that some genetic risk factors may be shared across diseases-as is the case with alleles in the Major Histocompatibility Locus. In this work we evaluate the extent of this sharing for 107 immune disease-risk SNPs in seven diseases: celiac disease, Crohn's disease, multiple sclerosis, psoriasis, rheumatoid arthritis, systemic lupus erythematosus, and type 1 diabetes. We have developed a novel statistic for Cross Phenotype Meta-Analysis (CPMA) which detects association of a SNP to multiple, but not necessarily all, phenotypes. With it, we find evidence that 47/107 (44%) immune-mediated disease risk SNPs are associated to multiple-but not all-immune-mediated diseases (SNP-wise P(CPMA)