New Crohn's disease susceptibility gene discovered

January 4, 2007

The following recent study represents a significant new discovery

which helps clarify the genetic basis of Crohn's disease. The new

gene identified seems to play a role in defense against bacteria, and

seems to interact with the CARD15 gene previously found to be a

Crohn's disease susceptibility gene.

Nat Genet. 2006 Dec 31; [Epub ahead of print]

A genome-wide association scan of nonsynonymous SNPs identifies a

susceptibility variant for Crohn disease in ATG16L1.

Hampe J, e A, Rosenstiel P, Till A, Teuber M, Huse K, Albrecht

M, Mayr G, De La Vega FM, Briggs J, Gunther S, Prescott NJ, Onnie CM,

Hasler R, Sipos B, Folsch UR, Lengauer T, Platzer M, Mathew CG,

Krawczak M, Schreiber S

[1] Institute for Clinical Molecular Biology, Christian-Albrechts

University Kiel, University Hospital Schleswig-Holstein, 24105 Kiel,

Germany. [2] First Department of Medicine, Christian-Albrechts

University Kiel, University Hospital Schleswig-Holstein, 24105 Kiel,

Germany. [3] These authors contributed equally to this work.

We performed a genome-wide association study of 19,779 nonsynonymous

SNPs in 735 individuals with Crohn disease and 368 controls. A total

of 7,159 of these SNPs were informative. We followed up on all 72

SNPs with P </= 0.01 with an allele-based disease association test in

380 independent Crohn disease trios, 498 Crohn disease singleton

cases and 1,032 controls. Disease association of rs2241880 in the

autophagy-related 16-like 1 gene (ATG16L1) was replicated in these

samples (P = 4.0 x 10(-8)) and confirmed in a UK case-control sample

(P = 0.0004). By haplotype and regression analysis, we found that

marker rs2241880, a coding SNP (T300A), carries virtually all the

disease risk exerted by the ATG16L1 locus. The ATG16L1 gene encodes a

protein in the autophagosome pathway that processes intracellular

bacteria. We found a statistically significant interaction with

respect to Crohn disease risk between rs2241880 and the established

CARD15 susceptibility variants (P = 0.039). Together with the lack of

association between rs2241880 and ulcerative colitis (P > 0.4), these

data suggest that the underlying biological process may be specific

to Crohn disease. PMID: 17200669.

SNPs = single nucleotide polymorphisms

Best regards,

Dave

(father of (21); PSC 07/03; UC 08/03)

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