An admixture mapping meta-analysis implicates genetic variation at 18q21 with asthma susceptibility in Latinos
Gignoux CR, Torgerson DG, Pino-Yanes M, Uricchio LH, Galanter J, Roth LA, Eng C, Hu D, Nguyen EA, Huntsman S, Mathias RA, Kumar R, Rodriguez-Santana J, Thakur N, Oh SS, McGarry M, Moreno-Estrada A, Sandoval K, Winkler CA, Seibold MA, Padhukasahasram B, Conti DV, Farber HJ, Avila P, Brigino-Buenaventura E, Lenoir M, Meade K, Serebrisky D, Borrell LN, Rodriguez-Cintron W, Thyne S, Joubert BR, Romieu I, Levin AM, Sienra-Monge JJ, Del Rio-Navarro BE, Gan W, Raby BA, Weiss ST, Bleecker E, Meyers DA, Martinez FJ, Gauderman WJ, Gilliland F, London SJ, Bustamante CD, Nicolae DL, Ober C, Sen S, Barnes K, Williams LK, Hernandez RD, Burchard EG. An admixture mapping meta-analysis implicates genetic variation at 18q21 with asthma susceptibility in Latinos. J Allergy Clin Immunol. 2019 Mar;143(3):957-969
The Journal of allergy and clinical immunology
BACKGROUND: Asthma is a common but complex disease with racial/ethnic differences in prevalence, morbidity, and response to therapies.
OBJECTIVE: We sought to perform an analysis of genetic ancestry to identify new loci that contribute to asthma susceptibility.
METHODS: We leveraged the mixed ancestry of 3902 Latinos and performed an admixture mapping meta-analysis for asthma susceptibility. We replicated associations in an independent study of 3774 Latinos, performed targeted sequencing for fine mapping, and tested for disease correlations with gene expression in the whole blood of more than 500 subjects from 3 racial/ethnic groups.
RESULTS: We identified a genome-wide significant admixture mapping peak at 18q21 in Latinos (P = 6.8 × 10
CONCLUSION: Ancestry at 18q21 was significantly associated with asthma in Latinos and implicated multiple ancestry-informative noncoding variants upstream of SMAD2 with asthma susceptibility. Furthermore, decreased SMAD2 expression in blood was strongly associated with increased asthma risk and increased exacerbations.