biostudies-literatureZhang WNIDDK NIH HHSNCRR NIH HHSCrohn's & Colitis FoundationNIGMS NIH HHS310-6https://www.ebi.ac.uk/biostudies/studies/S-EPMC3785105biostudies-literatureUnknown14(5)The Ashkenazi Jewish population has a several-fold higher prevalence of Crohn's disease (CD) compared with non-Jewish European ancestry populations and has a unique genetic history. Haplotype association is critical to CD etiology in this population, most notably at NOD2, in which three causal, uncommon and conditionally independent NOD2 variants reside on a shared background haplotype. We present an analysis of extended haplotypes that showed significantly greater association to CD in the Ashkenazi Jewish population compared with a non-Jewish population (145 haplotypes and no haplotypes with P-value <10(-3), respectively). Two haplotype regions, one each on chromosomes 16 and 21, conferred increased disease risk within established CD loci. We performed exome sequencing of 55 Ashkenazi JewGenes and immunityExtended haplotype association study in Crohn's disease identifies a novel, Ashkenazi Jewish-specific missense mutation in the NF-κB pathway gene, HEATR3.PMC3785105U01 DK062431R01 DK77905KL2 RR024138R01 DK061707RC1 DK086800T32 GM007205F30 DK098927U01 DK062423U01 DK0624222229P01 DK072201R01 DK077905R01 DK092235U01 DK062429KL2RR024138Abraham CMayer LDesnick RJCardinale CJWaterman MWarner NNunez GPeter IBurberry AChoi MHui KYCho JHFerguson JChowers YZhao HGregersen PKSilverberg MSKatz SPe'er IZhang WGusev AHakonarson HBrant SRNg SMKarban ALifton RPfalseExtended haplotype association study in Crohn's disease identifies a novel, Ashkenazi Jewish-specific missense mutation in the NF-κB pathway gene, HEATR3.The Ashkenazi Jewish population has a several-fold higher prevalence of Crohn's disease (CD) compared with non-Jewish European ancestry populations and has a unique genetic history. Haplotype association is critical to CD etiology in this population, most notably at NOD2, in which three causal, uncommon and conditionally independent NOD2 variants reside on a shared background haplotype. We present an analysis of extended haplotypes that showed significantly greater association to CD in the Ashkenazi Jewish population compared with a non-Jewish population (145 haplotypes and no haplotypes with P-value <10(-3), respectively). Two haplotype regions, one each on chromosomes 16 and 21, conferred increased disease risk within established CD loci. We performed exome sequencing of 55 Ashkenazi Jew2013-01-01T00:00:00Z2013 Jul-Aug2026-04-08T01:19:21.83Z2019-03-27T01:16:37ZS-EPMC37851052361507210.1038/gene.2013.19