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A genome-wide scan of ashkenazi jewish crohn's disease suggests novel susceptibility loci

Kenny, EE and Pe'er, I and Karban, A and Ozelius, L and Mitchell, AA and Ng, SM and Erazo, M and Ostrer, H and Abraham, C and Abreu, MT and Atzmon, G and Barzilai, N and Brant, SR and Bressman, S and Burns, ER and Chowers, Y and Clark, LN and Darvasi, A and Doheny, D and Duerr, RH and Eliakim, R and Giladi, N and Gregersen, PK and Hakonarson, H and Jones, MR and Marder, K and McGovern, DPB and Mulle, J and Orr-Urtreger, A and Proctor, DD and Pulver, A and Rotter, JI and Silverberg, MS and Ullman, T and Warren, ST and Waterman, M and Zhang, W and Bergman, A and Mayer, L and Katz, S and Desnick, RJ and Cho, JH and Peter, I (2012) A genome-wide scan of ashkenazi jewish crohn's disease suggests novel susceptibility loci. PLoS Genetics, 8 (3). ISSN 1553-7390

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Abstract

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<5×10 -6). Novel signals detected among AJs were mapped to chromosomes 5q21.1 (rs7705924, combined p = 2×10 -8; combined odds ratio OR = 1.48), 2p15 (rs6545946, p = 7×10 -9; OR = 1.16), 8q21.11 (rs12677663, p = 2×10 -8; OR = 1.15), 10q26.3 (rs10734105, p = 3×10 -8; OR = 1.27), and 11q12.1 (rs11229030, p = 8×10 -9; OR = 1.15), implicating biologically plausible candidate genes, including RPL7, CPAMD8, PRG2, and PRG3. In all, the 16 replicated and newly discovered loci, in addition to the three coding NOD2 variants, accounted for 11.2% of the total genetic variance for CD risk in the AJ population. This study demonstrates the complementary value of genetic studies in the Ashkenazim. © 2012 Kenny et al.


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Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Kenny, EE
Pe'er, I
Karban, A
Ozelius, L
Mitchell, AA
Ng, SM
Erazo, M
Ostrer, H
Abraham, C
Abreu, MT
Atzmon, G
Barzilai, N
Brant, SR
Bressman, S
Burns, ER
Chowers, Y
Clark, LN
Darvasi, A
Doheny, D
Duerr, RHduerr@pitt.eduDUERR
Eliakim, R
Giladi, N
Gregersen, PK
Hakonarson, H
Jones, MR
Marder, K
McGovern, DPB
Mulle, J
Orr-Urtreger, A
Proctor, DD
Pulver, A
Rotter, JI
Silverberg, MS
Ullman, T
Warren, ST
Waterman, M
Zhang, W
Bergman, A
Mayer, L
Katz, S
Desnick, RJ
Cho, JH
Peter, I
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorAbecasis, Goncalo R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Date: 1 March 2012
Date Type: Publication
Journal or Publication Title: PLoS Genetics
Volume: 8
Number: 3
DOI or Unique Handle: 10.1371/journal.pgen.1002559
Schools and Programs: Graduate School of Public Health > Human Genetics
Refereed: Yes
ISSN: 1553-7390
MeSH Headings: Chromosomes, Human, Pair 5--genetics; Cohort Studies; Crohn Disease--genetics; European Continental Ancestry Group; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Jews--genetics; Linkage Disequilibrium
Other ID: NLM PMC3297573
PubMed Central ID: PMC3297573
PubMed ID: 22412388
Date Deposited: 13 Sep 2012 18:29
Last Modified: 22 Dec 2019 06:55
URI: http://d-scholarship.pitt.edu/id/eprint/14151

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