Role of Sex on the Genetic Susceptibility to Childhood Asthma in Latinos and African Americans.
Role of Sex on the Genetic Susceptibility to Childhood Asthma in Latinos and African Americans.
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DOI：
10.3390/jpm11111140
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发表时间：
2021-11-03
影响因子：
--
通讯作者：
Pino-Yanes M
中科院分区：
文献类型：
--
作者：
Espuela-Ortiz A;Herrera-Luis E;Lorenzo-Díaz F;Hu D;Eng C;Villar J;Rodriguez-Santana JR;Burchard EG;Pino-Yanes M
哮喘是一种呼吸道疾病，其患病率在整个生命周期中发生变化，并因性别而异，在儿童时期男性和青春期后女性中更为普遍。在这项研究中，我们评估了性别对混合人群中儿童哮喘遗传易感性的影响。在4291名拉丁裔和1730名非洲裔美国人中分别进行了性别交互和性别分层全基因组关联研究（GWAS），并对结果进行了荟萃分析。全基因组（p ≤ 9.35 × 10−8）和提示性（p ≤ 1.87 × 10−6）群体特异性显著性阈值是根据1000个基因组计划数据计算的。此外，蛋白质数量性状基因座（pQTL）的信息收集的连锁相关的变体，并进行富集分析的蛋白质鉴定。四个独立的基因座显示与性别的相互作用在一个暗示的水平。分层的GWAS强调了17 q12 -21哮喘基因座是男女哮喘易感性的贡献者，但仅在女性中达到全基因组显著性（p-女性< 9.2 × 10−8; p-男性< 1.25 × 10−2）。相反，先前参与身高决定和精子发生的配体依赖性核受体辅阻遏物样基因（LCORL）上游的遗传变异仅与男性哮喘相关（rs 4593128的最小p = 5.31 × 10−8）。富集分析显示，与免疫系统有关的过程过多，并突出了性别之间的差异。总之，我们确定了性别特异性多态性，这可能有助于儿童哮喘的患病率在男性和女性之间的差异。
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.
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DOI：
10.1186/1710-1492-5-6
发表时间：
2009-11-09
期刊：
Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology
影响因子：
--
作者：
Van Bever HP
通讯作者：
Van Bever HP
影响因子：
30.8
作者：
Das, Sayantan;Forer, Lukas;Schoenherr, Sebastian;Sidore, Carlo;Locke, Adam E.;Kwong, Alan;Vrieze, Scott I.;Chew, Emily Y.;Levy, Shawn;McGue, Matt;Schlessinger, David;Stambolian, Dwight;Loh, Po-Ru;Iacono, William G.;Swaroop, Anand;Scott, Laura J.;Cucca, Francesco;Kronenberg, Florian;Boehnke, Michael;Abecasis, Goncalo R.;Fuchsberger, Christian
通讯作者：
Fuchsberger, Christian
影响因子：
9.2
作者：
Chang CC;Chow CC;Tellier LC;Vattikuti S;Purcell SM;Lee JJ
通讯作者：
Lee JJ
影响因子：
14.2
作者：
Loisel, Dagan A.;Tan, Zheng;Ober, Carole
通讯作者：
Ober, Carole
影响因子：
5
作者：
Gauderman, W. James;Kim, Andre;Lewinger, Juan Pablo
通讯作者：
Lewinger, Juan Pablo