Re: Genome-Wide Association Study Identifies African-Specific Susceptibility Loci in African Americans With Inflammatory Bowel Disease

Abstract

We read with great interest the original article by Brant et al.1Brant S.R. et al.Gastroenterology. 2017; 152: 206-217Abstract Full Text Full Text PDF PubMed Scopus (86) Google Scholar The discovery of African American (AA)-specific loci and loci that are shared between ethnic groups highlight the importance of studying inflammatory bowel disease in other populations apart from Europeans for a unique insight into the pathogenesis of inflammatory bowel disease. The challenges with studying populations of non-European ancestry remains one of terminology. The main drawback is that the difference between race and ethnicity is not clearly defined in most studies. Further discrepancies arise when considering the genetic background. For instance the African American race, is collectively grouped as one, irrespective of the country of origin reflecting different genetic backgrounds. It is not surprising that phenotype studies in Hispanic2Damas O.M. et al.Am J Gastroenterol. 2013; 108: 231-239Crossref PubMed Scopus (50) Google Scholar and South Asians populations3Jayanthi V. et al.Digestion. 1992; 52: 34-42Crossref PubMed Scopus (24) Google Scholar have previously shown discordant results as the groups consist of a heterogenous population. “Hispanics” refers to people from Mexico, Cuba, and Puerto Rico and reflects a social construct rather than common genetic background. Similarly, South Asians encompass a broad population from different genetic backgrounds to include India, Pakistan, Bangladesh, and Sri Lanka. Clearer descriptors are needed to incorporate genetic as well as ethnic aspects of these groups as both influence disease expression. So although the authors describe the potential for identifying risk prediction for AA, this may not be applicable to all patients as the term reflects a broad racial group and ignores genetic origin and ethnic factors. The South Asian (SA) population draws parallels with the AA population. Juyal et al4Juyal G. et al.Gut. 2015; 64: 571-579Crossref PubMed Scopus (43) Google Scholar reported the first genome-wide association study of ulcerative colitis (UC) in a genetically distinct north Indian population. They identified novel UC risk loci specific to the North Indian population as well as a shared contribution of a proportion of UC susceptibility genes with the European population. An additional dimension to race and ethnicity is the relationship to migration. Migrants settling in a new country may be construed as a race when they integrate with the indigenous population, but where they converge and create into their own social communities they are referred to as by ethnic group. The UK experienced large-scale migration from South Asia in the 1960s and 1970s with the establishment of a mature population of first and second generation SA migrants. Migration offers a unique opportunity to examine how environmental factors impinge on new migrants resulting in disease presentation. A higher incidence of UC was observed in the SA population with differences in disease phenotype, whereby second-generation migrants showed more pancolonic disease.5Probert CS, et al. Gut 1992;33:687–693.Google Scholar, 6Carr I. et al.Am J Gastroenterol. 1999; 94: 2918-2922Crossref PubMed Google Scholar, 7Carroll M.W. et al.Inflamm Bowel Dis. 2016; 22: 387-396Crossref PubMed Scopus (13) Google Scholar The latter observation would indicate an environmental influence on a genetically susceptible group and yet the genetics of the wider SA group differ. Although there are several challenges and caveats with migrant, race, and ethnic studies, it would be interesting to explore further whether dispersed migrants who are defined as a race differ from the migrants who cluster in ethnic groups and whether the difference are captured in pathophysiology. Although this may not apply to AAs, it maybe easier to study in the SA communities living in the United Kingdom and Canada. Aligning the differences with a molecular signature for ethnic groups has a tremendous potential to discover unique markers for disease triggers, diagnosis, prognosis, and prediction of therapeutic response for personalized medicine. Genome-Wide Association Study Identifies African-Specific Susceptibility Loci in African Americans With Inflammatory Bowel DiseaseGastroenterologyVol. 152Issue 1PreviewThe 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. Full-Text PDF ReplyGastroenterologyVol. 152Issue 8PreviewWe thank the authors for their interest in our original article.1 We have read their argument and we offer responses on 2 main points: (1) “The challenges with studying populations of non-European ancestry remains one of terminology” and (2) “So although the authors describe the potential for identifying risk prediction for AA [African Americans], this may not be applicable to all patients as the term reflects a broad racial group and ignores genetic origin and ethnic factors.” Full-Text PDF