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.
Highlights
IntroductionMeta-analyses of genome-wide association studies (GWAS) by an international effort have identified over 160 genomic regions contributing to the inflammatory bowel diseases (IBD), Crohn’s disease (CD) and ulcerative colitis (UC) in populations of European descent.[1,2,3] Many of these genes overlap with genes for other immune-related traits such as psoriasis and ankylosing spondylitis.Studies of populations of African and Asian descent suggest that the study of IBD genetics in non-European populations may show: 1) same gene, same SNPs, but stronger effects than what has been observed in populations of European descent, for example TNFSF15; [4,5] 2) same gene, different SNPs than what has been observed in populations of European descent, for example NOD2; [6] as well as 3) different gene, different SNPs contributing to susceptibility. [7] When taken together with the large number of mouse models of intestinal inflammation, these human results support the concept that multiple pathways lead to intestinal inflammation, and that, just as in different mouse strains, different combinations of susceptibility loci may act in different human populations. [8,9].Populations from three continents have contributed to the current genetic composition of Puerto Rico
Studies of populations of African and Asian descent suggest that the study of inflammatory bowel disease (IBD) genetics in non-European populations may show: 1) same gene, same SNPs, but stronger effects than what has been observed in populations of European descent, for example TNFSF15; [4,5] 2) same gene, different SNPs than what has been observed in populations of European descent, for example NOD2; [6] as well as 3) different gene, different SNPs contributing to susceptibility
Note that in this paper, ‘‘America’’ is an abbreviation to refer to the terms ‘‘Ancient Americans,’’ ‘‘Native Americans’’ or ‘‘Meso-Americans.’’ The estimates for African and American continental proportions were used as covariates to correct for global admixture in the analyses described below
Summary
Meta-analyses of genome-wide association studies (GWAS) by an international effort have identified over 160 genomic regions contributing to the inflammatory bowel diseases (IBD), Crohn’s disease (CD) and ulcerative colitis (UC) in populations of European descent.[1,2,3] Many of these genes overlap with genes for other immune-related traits such as psoriasis and ankylosing spondylitis.Studies of populations of African and Asian descent suggest that the study of IBD genetics in non-European populations may show: 1) same gene, same SNPs, but stronger effects than what has been observed in populations of European descent, for example TNFSF15; [4,5] 2) same gene, different SNPs than what has been observed in populations of European descent, for example NOD2; [6] as well as 3) different gene, different SNPs contributing to susceptibility. [7] When taken together with the large number of mouse models of intestinal inflammation, these human results support the concept that multiple pathways lead to intestinal inflammation, and that, just as in different mouse strains, different combinations of susceptibility loci may act in different human populations. [8,9].Populations from three continents have contributed to the current genetic composition of Puerto Rico. [11] Import of slaves from West Africa began in 1513 in order to keep the sugar industry economically viable; in the same year Spanish citizens were granted the right to marry Taıno by the Spanish crown. Multiple migrations of both Puerto Ricans and of Africans have occurred back and forth across the Caribbean up to the present day.
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