Association study in African-admixed populations across the Americas recapitulates asthma risk loci in non-African populations
Daya M, Rafaels N, Brunetti TM, Chavan S, Levin AM, Shetty A, Gignoux CR, Boorgula MP, Wojcik G, Campbell M, Vergara C, Torgerson DG, Ortega VE, Doumatey A, Johnston HR, Acevedo N, Araujo MA, Avila PC, Belbin G, Bleecker ER, Bustamante C, Caraballo L, Cruz AA, Dunston GM, Eng C, Faruque MU, Ferguson TS, Figueiredo C, Ford JG, Gan W, Gourraud P, Hansel N, Hernandez R, Herrera-Paz EP, Jimenez S, Kenny EE, Knight-Madden J, Kumar R, Lange LE, Lange EM, Lizee A, Maul P, Maul T, Mayorga Sirera AJ, Meyers DA, Nicolae DL, Oliveira RR, Olopade CO, Olopade O, Qin ZS, Rotimi C, Vince N, Watson H, Wilks RJ, Wilson JG, Salzberg S, Ober C, Burchard EG, Williams KL, Beaty TH, Taub MA, Ruczinski I, Mathias RA, Barnes KC. Association study in African-admixed populations across the Americas recapitulates asthma risk loci in non-African populations. J Allergy Clin Immunol 2019; 143(2):AB296.
J Allergy Clin Immunol
Rationale: Asthma is a complex disease with striking disparities across racial and ethnic groups. Despite its high burden, representation of African ancestry individuals in asthma genome-wide association studies (GWAS) has been inadequate to date, and true associations in these underrepresented minority groups may have been missed. Here, we report the largest asthma GWAS to date from the Consortium on Asthma among African Ancestry Populations (CAAPA). Methods: CAAPA participants (7009 asthmatics, 7645 controls) were genotyped using the African Diaspora Power Chip (ADPC), an array designed to complement existing genome-wide array data, as well as Illumina’s Multi-Ethnic Genotyping array. Genotypes were imputed using the CAAPA whole genome-sequence reference panel. Logistic mixed effects models were used to test for association between allelic dosage and asthma, separately for each study. Results were meta-analyzed using a meta-regression approach that accounts for heterogeneity in allelic effects among ethnic groups. Results: We identified two novel loci that may be specific to asthma risk in African ancestry populations (lead SNP rs13277810, intronic to LOC101927815, p=3E-8; lead SNP rs114647118, intronic to TATDN1, p=3E-7). We found strong evidence for association at four previously reported asthma loci whose discovery was driven largely by non-African populations (p<0.05/810 candidate SNPs investigated), including the chr12q13 region, a novel locus identified by the Trans-National Asthma Genetic Consortium (TAGC) that has previously not been replicated. Conclusions: We report two associations that may bespecific to asthma risk in African ancestry populations. Our results also suggest some asthma risk loci discovered in non-African populations are relevant in African ancestry populations.