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Backgrounds: Recent studies have identified the role of serologic markers in characterizing disease phenotype, location, complications, and severity among Northern Europeans (NE) with Crohn's disease (CD). However, very little is known about the role of serology in CD among African Americans (AA). Our study explored the relationship between serology and disease phenotype in AA with CD, while controlling for genetic ancestry., Methods: AAs with CD were enrolled as participants through multicenter collaborative efforts. Serological levels of IgA anti-Saccharomyces cervisiae antibody (ASCA), IgG ASCA, E. coli outermembrane porin C, anti-CBir1, and ANCA were measured using enzyme-linked immunosorbent assays. Genotyping was performed using Illumina immunochip technology; an admixture rate was calculated for each subject. Multiple imputation by chained equations was performed to account for data missing at random. Logistic regression was used to calculate adjusted odds ratio (OR) for associations between serological markers and both complicated disease and disease requiring surgery., Results: A total of 358 patients were included in the analysis. The majority of our patients had inflammatory, noncomplicated disease (58.4%), perianal disease (55.7%), and documented colonic inflammation (86.8%). On multivariable analysis, both IgG ASCA and OmpC were associated with complicated disease (OR, 2.67; 95% CI, 1.67-4.28; OR, 2.23; 95% CI, 1.41-3.53, respectively) and disease requiring surgery (OR, 2.51; 95% CI, 1.49-4.22; OR, 3.57; 95% CI, 2.12-6.00). NE admixture to the African genome did not have any associations or interactions in relation to clinical outcome., Conclusions: Our study comprises the largest cohort of AAs with CD. The utility of serological markers for the prognosis of CD in NE applies equally to AA populations., (© 2017 Crohn’s & Colitis Foundation of America. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com)

Background & Aims: The inflammatory bowel diseases (IBD) ulcerative colitis (UC) and Crohn's disease (CD) cause significant morbidity and are increasing in prevalence among all populations, including African Americans. More than 200 susceptibility loci have been identified in populations of predominantly European ancestry, but few loci have been associated with IBD in other ethnicities., Methods: We performed 2 high-density, genome-wide scans comprising 2345 cases of African Americans with IBD (1646 with CD, 583 with UC, and 116 inflammatory bowel disease unclassified) and 5002 individuals without IBD (controls, identified from the Health Retirement Study and Kaiser Permanente database). Single-nucleotide polymorphisms (SNPs) associated at P < 5.0 × 10 -8 in meta-analysis with a nominal evidence (P < .05) in each scan were considered to have genome-wide significance., Results: We detected SNPs at HLA-DRB1, and African-specific SNPs at ZNF649 and LSAMP, with associations of genome-wide significance for UC. We detected SNPs at USP25 with associations of genome-wide significance for IBD. No associations of genome-wide significance were detected for CD. In addition, 9 genes previously associated with IBD contained SNPs with significant evidence for replication (P < 1.6 × 10 -6 ): ADCY3, CXCR6, HLA-DRB1 to HLA-DQA1 (genome-wide significance on conditioning), IL12B,PTGER4, and TNC for IBD; IL23R, PTGER4, and SNX20 (in strong linkage disequilibrium with NOD2) for CD; and KCNQ2 (near TNFRSF6B) for UC. Several of these genes, such as TNC (near TNFSF15), CXCR6, and genes associated with IBD at the HLA locus, contained SNPs with unique association patterns with African-specific alleles., Conclusions: We performed a genome-wide association study of African Americans with IBD and identified loci associated with UC in only this population; we also replicated IBD, CD, and UC loci identified in European populations. The detection of variants associated with IBD risk in only people of African descent demonstrates the importance of studying the genetics of IBD and other complex diseases in populations beyond those of European ancestry., Competing Interests: The authors have no conflicts to declare., (Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background and Objective: Whether race affects the natural history of Crohn's disease is a matter of debate. The aim of the current study was to evaluate the differences in surgical outcomes between African-American (AA) and Caucasian (C) Crohn's patients undergoing surgery at a tertiary care referral center., Methods: With Institutional Review Board approval, the medical records of our institution were queried to identify consecutive AA and C patients who underwent surgery for Crohn's disease from December 1, 2009 to December 15, 2011. A retrospective chart review was performed using electronic medical records., Results: A total of 77 patients were included in this study, including 32 AA (41 %) and 45 C (59 %). No significant differences were seen with respect to age, gender, type of insurance, preoperative exposure to immunosuppressives, body mass index, or smoking history between the two populations (p > 0.05). There was a trend toward lower albumin in AAs (p = 0.09). AA and C patients who underwent their first Crohn's disease (CD)-related surgery had similar lag periods between diagnosis and surgery. No significant differences were seen in location of disease, indication for operation, and need for open laparotomy over laparoscopy. No significant differences were seen in need for a repeat operation within 90 days of the original surgery or major postoperative complications. There was a trend toward higher rate of minor complications in the AA group (p = 0.07)., Conclusion: No significant differences were noted in the current study in several preoperative variables and surgical outcomes between AA and C.

Background: Vitamin D deficiency and low bone mineral density (BMD) are complications of inflammatory bowel disease. Vitamin D deficiency is more prevalent among African Americans compared with whites. There are little data comparing differences in serum 25-hydroxyvitamin D (25OHD) concentrations and BMD between African American and white children with Crohn disease (CD)., Methods: We compared serum 25OHD concentrations of African American children with CD (n = 52) to white children with CD (n = 64) and healthy African American controls (n = 40). We also analyzed BMD using dual-energy x-ray absorptiometry results from our pediatric CD population., Results: African American children with CD had lower serum 25OHD concentrations (16.1 [95% confidence interval, CI 14.5-17.9] ng/mL) than whites with CD (22.3 [95% CI 20.2-24.6] ng/mL; P < 0.001). African Americans with CD and controls exhibited similar serum 25OHD concentration (16.1 [95% CI 14.5-17.9] vs 16.3 [95% CI 14.4-18.4] ng/mL; NS). African Americans with CD exhibited no difference in serum 25OHD concentration when controlling for seasonality, disease severity, and surgical history, although serum 25OHD concentration was significantly decreased in overweight children (body mass index ≥85%, P = 0.003). Multiple regression analysis demonstrated that obese African American girls with CD had the lowest serum 25OHD concentrations (9.6 [95% CI 6.8-13.5] ng/mL). BMD was comparable between African American and white children with CD (z score -0.4 ± 0.9 vs -0.7 ± 1.2; NS)., Conclusions: African American children with CD are more likely to have vitamin D deficiency compared with white children with CD, but have similar BMD. CD disease severity and history of surgery do not affect serum 25OHD concentrations among African American children with CD. African American children have low serum 25OHD concentrations, independent of CD, compared with white children. Future research should focus on how race affects vitamin D status and BMD in children with CD.

Background: Crohn's disease (CD) is highly heritable. NOD2 has emerged as the main susceptibility gene among individuals of European ancestry; however, NOD2 does not appear to contribute to CD susceptibility among many non-European populations. Today's African American (AA) population represents an admixture of West African (80%) and European (20%) ancestry. Since genotype-based tools are becoming increasingly available for CD, it is important that we validate the risk variants in different populations, such as admixed AAs., Methods: We analyzed the NOD2 variants among admixed AAs (n = 321, 240 with CD and 111 healthy controls [HCs]) and nonadmixed West Africans (n = 40) by genotyping four known disease-causing NOD variants. We extracted the publicly available 1000 Genomes data on NOD2 variants from 500 subjects of West African origin. Association with disease was evaluated by logistic regression., Results: An association with CD was found for the classical single nucleotide polymorphism (SNP) 1007fs (2.6% CD, 0% HC, P = 0.012); there was no association when the genotypic and allelic frequencies of the risk alleles were compared for SNPs R702W and G908R. No known NOD2 risk alleles were seen in either the West African cohort or in subjects of African ancestry from the 1000 Genomes project., Conclusions: The NOD2 gene is a risk for CD in AAs, although the allele frequencies and the attributable risk are much lower compared with Caucasians. The risk alleles are not seen in the West African population, suggesting that the risk for CD contributed by NOD2 among AAs is due exclusively to recent European admixture., (Copyright © 2012 Crohn's & Colitis Foundation of America, Inc.)

Objective: African-Americans have been underrepresented in most large Crohn's disease (CD) trials. This study was undertaken to assess the course and character of CD in African-Americans in comparison with whites., Methods: We retrospectively compared the course and character of CD in African-American and white patients at 3 Atlanta hospitals. Ninety-nine patients (55 African-American, 44 whites) were enrolled. Telephone interviews and chart reviews were used to identify disease location, presence of fistulae and perirectal disease, surgical history, and medication use. Patients with ulcerative colitis or indeterminant colitis, and all non-African-Americans or whites, were excluded., Results: The numbers of male and female patients were similar (50 and 49). Overall, men comprised 54% of white patients and 47% of African-American patients. There were no significant differences in the setting in which CD were diagnosed, number of flares per year, or duration of symptoms before diagnosis. White patients were more likely to seek care for their CD in a clinic setting, both their primary care physicians (1.31 versus 0.21 visits/yr, P < 0.001) and their gastroenterologists (3.2 versus 2.3 visits/yr, P = 0.03). Small bowel (SB) disease was present more frequently in white patients, 84% versus 65% (P = 0.03), and SB resection was more common in this group, 59% versus 16% (P < 0.01). Colonic disease was more common in African-American patients, 89% versus 63% (P = 0.002). Perirectal fistulae were more frequent in African-American patients, 58% versus 22% (P < 0.001) white patients were more likely to report complete compliance with medical therapy, 77% versus 49% (P = 0.004). African-American patients more frequently discontinued medical therapy because they "felt better" (27% versus 9%, P = 0.02). Medication usage, including immunosuppressants, was similar in both groups, except that white patients were more likely to receive multiple doses of infliximab (34% versus 11%, P = 0.005). Both groups felt equally informed about CD, but white patients felt that their disease was under good control a greater percentage of the time, 71% versus 58% (P = 0.04)., Conclusions: These data lend credence to the suggestion that the nature of CD may be different in African-Americans compared with whites. However, despite this apparent difference in disease manifestation, the contribution of socioeconomic factors, access to health care, and understanding of the disease likely play a role as well.

Whether or not populations diverge with respect to the genetic contribution to risk of specific complex diseases is relevant to understanding the evolution of susceptibility and origins of health disparities. Here, we describe a large-scale whole-genome sequencing study of inflammatory bowel disease encompassing 1,774 affected individuals and 1,644 healthy control Americans with African ancestry (African Americans). Although no new loci for inflammatory bowel disease are discovered at genome-wide significance levels, we identify numerous instances of differential effect sizes in combination with divergent allele frequencies. For example, the major effect at PTGER4 fine maps to a single credible interval of 22 SNPs corresponding to one of four independent associations at the locus in European ancestry individuals but with an elevated odds ratio for Crohn disease in African Americans. A rare variant aggregate analysis implicates Ca2+-binding neuro-immunomodulator CALB2 in ulcerative colitis. Highly significant overall overlap of common variant risk for inflammatory bowel disease susceptibility between individuals with African and European ancestries was observed, with 41 of 241 previously known lead variants replicated and overall correlations in effect sizes of 0.68 for combined inflammatory bowel disease. Nevertheless, subtle differences influence the performance of polygenic risk scores, and we show that ancestry-appropriate weights significantly improve polygenic prediction in the highest percentiles of risk. The median amount of variance explained per locus remains the same in African and European cohorts, providing evidence for compensation of effect sizes as allele frequencies diverge, as expected under a highly polygenic model of disease.

Background & aimsInflammatory bowel disease (IBD) has familial aggregation in African Americans (AAs), but little is known about the molecular genetic susceptibility. Mapping studies using the Immunochip genotyping array expand the number of susceptibility loci for IBD in Caucasians to 163, but the contribution of the 163 loci and European admixture to IBD risk in AAs is unclear. We performed a genetic mapping study using the Immunochip to determine whether IBD susceptibility loci in Caucasians also affect risk in AAs and identify new associated loci.MethodsWe recruited AAs with IBD and without IBD (controls) from 34 IBD centers in the United States; additional controls were collected from 4 other Immunochip studies. Association and admixture loci were mapped for 1088 patients with Crohn's disease, 361 with ulcerative colitis, 62 with IBD type unknown, and 1797 controls; 130,241 autosomal single-nucleotide polymorphisms (SNPs) were analyzed.ResultsThe strongest associations were observed between ulcerative colitis and HLA rs9271366 (P = 7.5 × 10(-6)), Crohn's disease and 5p13.1 rs4286721 (P = 3.5 × 10(-6)), and IBD and KAT2A rs730086 (P = 2.3 × 10(-6)). Additional suggestive associations (P < 4.2 × 10(-5)) were observed between Crohn's disease and IBD and African-specific SNPs in STAT5A and STAT3; between IBD and SNPs in IL23R, IL12B, and C2orf43; and between ulcerative colitis and SNPs near HDAC11 and near LINC00994. The latter 3 loci have not been previously associated with IBD, but require replication. Established Caucasian associations were replicated in AAs (P < 3.1 × 10(-4)) at NOD2, IL23R, 5p15.3, and IKZF3. Significant admixture (P < 3.9 × 10(-4)) was observed for 17q12-17q21.31 (IZKF3 through STAT3), 10q11.23-10q21.2, 15q22.2-15q23, and 16p12.2-16p12.1. Network analyses showed significant enrichment (false discovery rate