A Genome-Wide Scan of Ashkenazi Jewish Crohn%26apos;s Disease Suggests Novel Susceptibility Loci

作者：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

来源：PLoS Genetics, 2012, 8(3): e1002559.

DOI：10.1371/journal.pgen.1002559

Crohn%26apos;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 %26lt; 5 x 10(-6)). Novel signals detected among AJs were mapped to chromosomes 5q21.1 (rs7705924, combined p = 2 x 10(-8); combined odds ratio OR = 1.48), 2p15 (rs6545946, p = 7 x 10(-9); OR = 1.16), 8q21.11 (rs12677663, p = 2 x 10(-8); OR = 1.15), 10q26.3 (rs10734105, p = 3 x 10(-8); OR = 1.27), and 11q12.1 (rs11229030, p = 8 x 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.

• 出版日期2012-3
• 单位河北医科大学