title: Association of NOD2 and IL23R with inflammatory bowel disease in Puerto Rico.
abstract: The Puerto Rico population may be modeled as an admixed population with contributions from three continents: Sub-Saharan Africa, Ancient America, and Europe. Extending the study of the genetics of inflammatory bowel disease (IBD) to an admixed population such as Puerto Rico has the potential to shed light on IBD genes identified in studies of European populations, find new genes contributing to IBD susceptibility, and provide basic information on IBD for the care of US patients of Puerto Rican and Latino descent. In order to study the association between immune-related genes and Crohn's disease (CD) and ulcerative colitis (UC) in Puerto Rico, we genotyped 1159 Puerto Rican cases, controls, and family members with the ImmunoChip. We also genotyped 832 subjects from the Human Genome Diversity Panel to provide data for estimation of global and local continental ancestry. Association of SNPs was tested by logistic regression corrected for global continental descent and family structure. We observed the association between Crohn's disease and NOD2 (rs17313265, 0.28 in CD, 0.19 in controls, OR 1.5, p = 9×10-6) and IL23R (rs11209026, 0.026 in CD, 0.0.071 in controls, OR 0.4, p = 3.8×10-4). The haplotype structure of both regions resembled that reported for European populations and "local" continental ancestry of the IL23R gene was almost entirely of European descent. We also observed suggestive evidence for the association of the BAZ1A promoter SNP with CD (rs1200332, 0.45 in CD, 0.35 in controls, OR 1.5, p = 2×10-6). Our estimate of continental ancestry surrounding this SNP suggested an origin in Ancient America for this putative susceptibility region. Our observations underscored the great difference between global continental ancestry and local continental ancestry at the level of the individual gene, particularly for immune-related loci.
authors.affiliation: Department of Medicine, Division of Gastroenterology, School of Medicine, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico.
authors.forename: Veroushka
authors.initials: V
authors.lastname: Ballester
authors.affiliation: Institute of Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor/UCLA Medical Center, Torrance, California, United States of America.
authors.forename: Xiuqing
authors.initials: X
authors.lastname: Guo
authors.affiliation: Department of Medicine, Division of Gastroenterology, School of Medicine, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico.
authors.forename: Roberto
authors.initials: R
authors.lastname: Vendrell
authors.affiliation: Medical Genetics Institute & Inflammatory Bowel Disease Center, Cedars-Sinai Medical Center, Los Angeles, California, United States of America.
authors.forename: Talin
authors.initials: T
authors.lastname: Haritunians
authors.affiliation: Institute of Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor/UCLA Medical Center, Torrance, California, United States of America.
authors.forename: Alexandra M
authors.initials: AM
authors.lastname: Klomhaus
authors.affiliation: Medical Genetics Institute & Inflammatory Bowel Disease Center, Cedars-Sinai Medical Center, Los Angeles, California, United States of America.
authors.forename: Dalin
authors.initials: D
authors.lastname: Li
authors.affiliation: Medical Genetics Institute & Inflammatory Bowel Disease Center, Cedars-Sinai Medical Center, Los Angeles, California, United States of America.
authors.forename: Dermot P B
authors.initials: DP
authors.lastname: McGovern
authors.affiliation: Institute of Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor/UCLA Medical Center, Torrance, California, United States of America.
authors.forename: Jerome I
authors.initials: JI
authors.lastname: Rotter
authors.affiliation: Department of Medicine, Division of Gastroenterology, School of Medicine, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico.
authors.forename: Esther A
authors.initials: EA
authors.lastname: Torres
authors.affiliation: Institute of Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor/UCLA Medical Center, Torrance, California, United States of America.
authors.forename: Kent D
authors.initials: KD
authors.lastname: Taylor
mesh_terms: D000328:Adult; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006239:Haplotypes; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011647:Puerto Rico; D040641:Quantitative Trait Loci; D018123:Receptors, Interleukin / Q000235:genetics*; D012307:Risk Factors; D055815:Young Adult
chemical_list: C515500:IL23R protein, human; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D018123:Receptors, Interleukin