An admixture mapping meta-analysis implicates genetic variation at 18q21 with asthma susceptibility in Latinos

Authors

Christopher R. Gignoux
Dara G. Torgerson
Maria Pino-Yanes
Lawrence H. Uricchio
Joshua Galanter
Lindsey A. Roth
Celeste Eng
Donglei Hu
Elizabeth A. Nguyen
Scott Huntsman
Rasika A. Mathias
Rajesh Kumar
Jose Rodriguez-Santana
Neeta Thakur
Sam S. Oh
Meghan McGarry
Andres Moreno-Estrada
Karla Sandoval
Cheryl A. Winkler
Max A. Seibold
Badri Padhukasahasram, Henry Ford Health
David V. Conti
Harold J. Farber
Pedro Avila
Emerita Brigino-Buenaventura
Michael Lenoir
Kelley Meade
Denise Serebrisky
Luisa N. Borrell
William Rodriguez-Cintron
Shannon Thyne
Bonnie R. Joubert
Isabelle Romieu
Albert M. Levin, Henry Ford Health SystemFollow
Juan-Jose Sienra-Monge
Blanca Estela Del Rio-Navarro
Weiniu Gan
Benjamin A Raby
Scott T Weiss
Eugene Bleecker
Deborah A MeyersFollow
Fernando J Martinez
W James Gauderman
Frank Gilliland
Stephanie J London
Carlos D Bustamante
Dan L Nicolae
Carole Ober
Saunak Sen
Kathleen Barnes
Keoki L. Williams, Henry Ford Health SystemFollow
Ryan D Hernandez
Esteban G Burchard

Recommended Citation

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

Document Type

Article

Publication Date

3-1-2019

Publication Title

The Journal of allergy and clinical immunology

Abstract

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.

PubMed ID

30201514

Volume

143

Issue

3

First Page

957

Last Page

969