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

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....

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Autores principales:	Antonio Espuela-Ortiz, Esther Herrera-Luis, Fabián Lorenzo-Díaz, Donglei Hu, Celeste Eng, Jesús Villar, Jose R. Rodriguez-Santana, Esteban G. Burchard, María Pino-Yanes
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	asthma sex interaction sex-stratified minority population Hispanic GWAS Medicine R
Acceso en línea:	https://doaj.org/article/d4b0c0ca74ba400480b47f2616411278
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spelling	oai:doaj.org-article:d4b0c0ca74ba400480b47f26164112782021-11-25T18:07:30ZRole of Sex on the Genetic Susceptibility to Childhood Asthma in Latinos and African Americans10.3390/jpm111111402075-4426https://doaj.org/article/d4b0c0ca74ba400480b47f26164112782021-11-01T00:00:00Zhttps://www.mdpi.com/2075-4426/11/11/1140https://doaj.org/toc/2075-4426Asthma 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 (<i>p</i> ≤ 9.35 × 10<sup>−8</sup>) and suggestive (<i>p</i> ≤ 1.87 × 10<sup>−6</sup>) 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 (<i>p</i>-females < 9.2 × 10<sup>−8</sup>; <i>p</i>-males < 1.25 × 10<sup>−2</sup>). Conversely, genetic variants upstream of ligand-dependent nuclear receptor corepressor-like gene (<i>LCORL</i>), previously involved in height determination and spermatogenesis, were associated with asthma only in males (minimum <i>p</i> = 5.31 × 10<sup>−8</sup> 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.Antonio Espuela-OrtizEsther Herrera-LuisFabián Lorenzo-DíazDonglei HuCeleste EngJesús VillarJose R. Rodriguez-SantanaEsteban G. BurchardMaría Pino-YanesMDPI AGarticleasthmasex interactionsex-stratifiedminority populationHispanicGWASMedicineRENJournal of Personalized Medicine, Vol 11, Iss 1140, p 1140 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	asthma sex interaction sex-stratified minority population Hispanic GWAS Medicine R
spellingShingle	asthma sex interaction sex-stratified minority population Hispanic GWAS Medicine R Antonio Espuela-Ortiz Esther Herrera-Luis Fabián Lorenzo-Díaz Donglei Hu Celeste Eng Jesús Villar Jose R. Rodriguez-Santana Esteban G. Burchard María Pino-Yanes Role of Sex on the Genetic Susceptibility to Childhood Asthma in Latinos and African Americans
description	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 (<i>p</i> ≤ 9.35 × 10<sup>−8</sup>) and suggestive (<i>p</i> ≤ 1.87 × 10<sup>−6</sup>) 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 (<i>p</i>-females < 9.2 × 10<sup>−8</sup>; <i>p</i>-males < 1.25 × 10<sup>−2</sup>). Conversely, genetic variants upstream of ligand-dependent nuclear receptor corepressor-like gene (<i>LCORL</i>), previously involved in height determination and spermatogenesis, were associated with asthma only in males (minimum <i>p</i> = 5.31 × 10<sup>−8</sup> 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.
format	article
author	Antonio Espuela-Ortiz Esther Herrera-Luis Fabián Lorenzo-Díaz Donglei Hu Celeste Eng Jesús Villar Jose R. Rodriguez-Santana Esteban G. Burchard María Pino-Yanes
author_facet	Antonio Espuela-Ortiz Esther Herrera-Luis Fabián Lorenzo-Díaz Donglei Hu Celeste Eng Jesús Villar Jose R. Rodriguez-Santana Esteban G. Burchard María Pino-Yanes
author_sort	Antonio Espuela-Ortiz
title	Role of Sex on the Genetic Susceptibility to Childhood Asthma in Latinos and African Americans
title_short	Role of Sex on the Genetic Susceptibility to Childhood Asthma in Latinos and African Americans
title_full	Role of Sex on the Genetic Susceptibility to Childhood Asthma in Latinos and African Americans
title_fullStr	Role of Sex on the Genetic Susceptibility to Childhood Asthma in Latinos and African Americans
title_full_unstemmed	Role of Sex on the Genetic Susceptibility to Childhood Asthma in Latinos and African Americans
title_sort	role of sex on the genetic susceptibility to childhood asthma in latinos and african americans
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/d4b0c0ca74ba400480b47f2616411278
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Role of Sex on the Genetic Susceptibility to Childhood Asthma in Latinos and African Americans

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