Admixture Mapping of Total Serum IgE in African American subjects from CAAPA
Sunday, March 4, 2018
South Hall A2 (Convention Center)
Michelle Daya, Aniket Shetty, Nicholas M Rafaels, Victor E Ortega, Eugene R Bleecker, Deborah A Meyers, Carole Ober, L. Keoki Williams, MD MPH FAAAAI, Margaret A Taub, Terri H Beaty, Ingo Ruczinski, Rasika A Mathias, Kathleen C Barnes
RATIONALE: Asthmatics of African descent have more severe asthma and higher total serum IgE (tIgE) levels compared to asthmatics of European ancestry. Admixture mapping is a powerful technique that leverages local ancestry to identify regions of the genome in admixed subjects where ancestry inherited from a particular ancestral population is associated with the phenotype of interest. Admixture mapping has not yet been used to map genetic loci influencing tIgE levels in African Americans.

METHODS: Local ancestry was estimated using RFMix. The analysis was then stratified by asthma case-control status and the originating study (5 studies from CAAPA, the Consortium on Asthma among African-ancestry Populations in the Americas) with 1,182 cases and 816 controls in total. Linear mixed effect models were used to test for association between the number of copies of African ancestry at each local ancestry segment and Studentized residuals of log10 transformed tIgE (adjusted for age and sex). Association test statistics from the stratified analysis were combined in an inverse-variance meta-analysis.

RESULTS: African ancestry was negatively correlated with tIgE at 8 local ancestry segments on chromosome 10p13-12.2, spanning 1,466,445 base pairs (P<1.9e-4, correcting for 262 independent tests). The CUBN gene in this region plays a role in Vitamin B12 absorption and is the only gene found in the peak segment (hg19 positions 16,948,177-17,055,370). It has been hypothesized Vitamin B12 deficiency plays a role in both asthma and atopic disease.

CONCLUSIONS: Our results suggest the CUBN gene affects tIgE levels in African Americans. Future work will include replication and fine-mapping.