A genome-wide scan of Ashkenazi Jewish Crohn's disease suggests novel susceptibility loci

Crohn's disease (CD) is a complex disorder resulting from the interaction of intestinal microbiota with the host immune system in genetically susceptible individuals. The largest meta-analysis of genome-wide association to date identified 71 CD-susceptibility loci in individuals of European anc...

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Bibliographic Details
Published in:PLoS genetics 2012-03, Vol.8 (3), p.e1002559-e1002559
Main Authors: Kenny, Eimear E, Pe'er, Itsik, Karban, Amir, Ozelius, Laurie, Mitchell, Adele A, Ng, Sok Meng, Erazo, Monica, Ostrer, Harry, Abraham, Clara, Abreu, Maria T, Atzmon, Gil, Barzilai, Nir, Brant, Steven R, Bressman, Susan, Burns, Edward R, Chowers, Yehuda, Clark, Lorraine N, Darvasi, Ariel, Doheny, Dana, Duerr, Richard H, Eliakim, Rami, Giladi, Nir, Gregersen, Peter K, Hakonarson, Hakon, Jones, Michelle R, Marder, Karen, McGovern, Dermot P B, Mulle, Jennifer, Orr-Urtreger, Avi, Proctor, Deborah D, Pulver, Ann, Rotter, Jerome I, Silverberg, Mark S, Ullman, Thomas, Warren, Stephen T, Waterman, Matti, Zhang, Wei, Bergman, Aviv, Mayer, Lloyd, Katz, Seymour, Desnick, Robert J, Cho, Judy H, Peter, Inga
Format: Article
Language:English
Subjects:
Bowel disease
Chromosomes
Chromosomes, Human, Pair 5 - genetics
Cohort Studies
Crohn Disease - genetics
Crohn's disease
Development and progression
Disease susceptibility
European Continental Ancestry Group
Genealogy
Genetic aspects
Genetic Predisposition to Disease
Genetics
Genome-Wide Association Study
Genomes
Humans
Immune system
Jewish people
Jews - genetics
Linkage Disequilibrium
Medicine
Meta-analysis
Parkinson's disease
Physiological aspects
Population
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Summary:Crohn's disease (CD) is a complex disorder resulting from the interaction of intestinal microbiota with the host immune system in genetically susceptible individuals. The largest meta-analysis of genome-wide association to date identified 71 CD-susceptibility loci in individuals of European ancestry. An important epidemiological feature of CD is that it is 2-4 times more prevalent among individuals of Ashkenazi Jewish (AJ) descent compared to non-Jewish Europeans (NJ). To explore genetic variation associated with CD in AJs, we conducted a genome-wide association study (GWAS) by combining raw genotype data across 10 AJ cohorts consisting of 907 cases and 2,345 controls in the discovery stage, followed up by a replication study in 971 cases and 2,124 controls. We confirmed genome-wide significant associations of 9 known CD loci in AJs and replicated 3 additional loci with strong signal (p
ISSN:1553-7404
1553-7390
1553-7404
DOI:10.1371/journal.pgen.1002559