Role of Sex on the Genetic Susceptibility to Childhood Asthma in Latinos and African Americans

Journal of Personalized Medicine

Jesús Villar¹  Jose R. Rodriguez-Santana²  Celeste Eng³  Esteban G. Burchard³  Donglei Hu³  Antonio Espuela-Ortiz⁴  Fabián Lorenzo-Díaz⁴  Esther Herrera-Luis⁴  María Pino-Yanes⁴ 

[1] CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, 28029 Madrid, Spain;Centro de Neumología Pediátrica, San Juan 00917, Puerto Rico;Department of Medicine, University of California San Francisco, San Francisco, CA 94158, USA;Genomics and Health Group, Department of Biochemistry, Microbiology, Cell Biology and Genetics, Universidad de La Laguna, 38200 San Cristóbal de La Laguna, Spain;

关键词: asthma;    sex interaction;    sex-stratified;    minority population;    Hispanic;    GWAS;   

DOI  :  10.3390/jpm11111140

来源: DOAJ

【 摘 要 】

Asthma is a respiratory disease whose prevalence changes throughout the lifespan and differs by sex, being more prevalent in males during childhood and in females after puberty. In this study, we assessed the influence of sex on the genetic susceptibility to childhood asthma in admixed populations. Sex-interaction and sex-stratified genome-wide association studies (GWAS) were performed in 4291 Latinos and 1730 African Americans separately, and results were meta-analyzed. Genome-wide (p ≤ 9.35 × 10⁻⁸) and suggestive (p ≤ 1.87 × 10⁻⁶) population-specific significance thresholds were calculated based on 1000 Genomes Project data. Additionally, protein quantitative trait locus (pQTL) information was gathered for the suggestively associated variants, and enrichment analyses of the proteins identified were carried out. Four independent loci showed interaction with sex at a suggestive level. The stratified GWAS highlighted the 17q12-21 asthma locus as a contributor to asthma susceptibility in both sexes but reached genome-wide significance only in females (p-females < 9.2 × 10⁻⁸; p-males < 1.25 × 10⁻²). Conversely, genetic variants upstream of ligand-dependent nuclear receptor corepressor-like gene (LCORL), previously involved in height determination and spermatogenesis, were associated with asthma only in males (minimum p = 5.31 × 10⁻⁸ for rs4593128). Enrichment analyses revealed an overrepresentation of processes related to the immune system and highlighted differences between sexes. In conclusion, we identified sex-specific polymorphisms that could contribute to the differences in the prevalence of childhood asthma between males and females.

【 授权许可】

Unknown