Prevalence of Celiac Disease-Compatible Human Leukocyte Antigen Haplotypes Across Ethnicities and Regions in the United States: 1181

INTRODUCTION: The prevalence of celiac disease (CD) is widely variable throughout the United States (US), with a higher prevalence of disease in the Northeast. The reasons for this variability are unknown. In a prior study, we detected ethnic differences within the US, using a name-based algorithm, with prevalence in patients of Jewish ethnicity similar to the overall population, and lower in persons of East Asian ethnicity. CD etiology is dependent on human leukocyte antigen (HLA) haplotype. Typically, either HLA DQ2.5 or DQ8 is required (but not sufficient) for the development of CD, with DQ2.5 being the highest-risk haplotype. To date, no study has characterized regional or ethnic differences in the frequency of CD-compatible HLA haplotypes. Thus, we aimed to measure the frequencies of DQ2.5 and DQ8 across regions and ethnicities in the US. METHODS: We assessed the frequencies of HLA DQ2.5 (DQA1*05:DQB1*02) and DQ8 (DQA1*03:DQB1*03) in an unselected group of genotyped individuals who have used direct-to-consumer genetic testing between 2013 and 2017. Eligible participants were 23andMe customers who consented to participate in research. We assayed two SNPs to classify individuals as DQ2.5 homozygous, DQ2.5 heterozygous, DQ2.5/DQ8, DQ8 homozygous, DQ8 heterozygous, and 0 detected variants. We compared the frequency of each haplotype across four regions of the US. Additionally, we used genome-wide array data to cluster participants into 8 categories that correlate highly with self-reported race and ethnicity, and compared the frequencies of these haplotypes across these ethnic categories (Table 1). RESULTS: Of 1,290,668 individuals studied, at least one CD-compatible haplotype was present in 38.7% of individuals, and this frequency was similar across the four US regions. The frequencies of DQ2.5 homozygotes were also similar across the Northeast, Midwest, South, and West (1.25%, 1.43%, 1.38%, and 1.37%, respectively). In contrast, frequencies differ across ethnic groups: the highest DQ2.5 and DQ8 frequencies were observed in European (12.01%) and Ashkenazi Jewish (16.39%) participants, respectively. CONCLUSION: Previously reported regional variability in CD prevalence in the US may not be due to differences in HLA-based susceptibility; rather, other genetic or environmental factors likely play a role in disease pathogenesis. In addition, these differences carry great significance in view of the development of HLA haplotype-specific non-dietary therapies for CD.