Genome-Wide Association Study of Korean Asthmatics: A Comparison With UK Asthmatics.
Genome-Wide Association Study of Korean Asthmatics: A Comparison With UK Asthmatics.
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DOI：
10.4168/aair.2021.13.4.609
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发表时间：
2021-07
期刊：
影响因子：
--
通讯作者：
Kim TB
中科院分区：
文献类型：
--
作者：
An J;Do AR;Kang HY;Kim WJ;Lee S;Lee JH;Song WJ;Kwon HS;Cho YS;Moon HB;Hu S;Adcock IM;Chung KF;Won S;Kim TB
虽然全基因组关联研究（GWAS）是识别影响哮喘的基因的最有力的方法，但迄今为止，还没有研究确定韩国人群对哮喘的遗传易感性。本研究旨在确定与韩国成人哮喘相关的遗传变异，并将其与英国生物库中英国哮喘患者的显著单核苷酸多态性（SNP）进行比较。患者被定义为患有哮喘，如果他们被医生诊断或服用哮喘药物。对照组被定义为没有哮喘或慢性阻塞性肺病的个体。我们进行了质量控制、基因型插补、GWAS和PrediXcan分析。在GWAS中，P值< 5 × 10−8被认为是显著的。我们比较了韩国和英国哮喘患者的显著SNPs。共分析了1，386名哮喘患者和5，205名对照。位于人类白细胞抗原（HLA）-DQB 1附近的SNP rs 1770是最显著的SNP（P = 4.5 × 10−10）。与英国哮喘患者GWAS中的24个SNP相比，6个SNP在相同的比值比（OR）方向上是显著的，包括与2型炎症相关的信号（例如，IL 1 RL 1、TSLP和GATA 3）和粘液堵塞（例如，MUC5AC）。HLA-DQA 1呈相反的OR方向。HLA-DQB 1基因在肺组织和全血中的mRNA表达显著增加。HLA-DQB 1位点rs 1770多态性在韩国哮喘患者中最显著。韩国和英国哮喘患者之间的遗传变异存在相似性和差异。朝鲜族哮喘患者的GWAS应重复并与其他种族的GWAS进行比较。
Although genome-wide association studies (GWASs) represent the most powerful approach for identifying genes that influence asthma, to date, no studies have established genetic susceptibility to asthma in the Korean population. This study aimed to identify genetic variants associated with adult Korean asthmatics and compare them with the significant single nucleotide polymorphisms (SNPs) of UK asthmatics from the UK Biobank. Patients were defined as having asthma if they were diagnosed by a doctor or taking medications for asthma. Controls were defined as individuals without asthma or chronic obstructive pulmonary disease. We performed quality control, genotype imputation, GWAS, and PrediXcan analyses. In the GWAS, a P value of < 5 × 10−8 was considered significant. We compared significant SNPs between Korean and UK patients with asthma. A total of 1,386 asthmatic patients and 5,205 controls were analyzed. The SNP rs1770, located near the human leukocyte antigen (HLA)-DQB1, was the most significant SNP (P = 4.5 × 10−10). In comparison with 24 SNPs in a GWAS of UK asthmatics, six SNPs were significant with the same odds ratio (OR) direction, including signals related to type 2 inflammation (e.g., IL1RL1, TSLP, and GATA3) and mucus plugging (e.g., MUC5AC). HLA-DQA1 showed an opposite OR direction. The HLA-DQB1 gene demonstrated significantly imputed mRNA expression in the lung tissue and whole blood. The SNP rs1770 of HLA-DQB1 was the most significant in Korean asthmatics. Similarities and discrepancies were found in the genetic variants between Korean and UK asthmatics. GWAS of Korean asthmatics should be replicated and compared with those of GWAS of other ethnicities.
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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：
8.7
作者：
Ober C;Yao TC
通讯作者：
Yao TC
影响因子：
30.8
作者：
Loh, Po-Ru;Danecek, Petr;Palamara, Pier Francesco;Fuchsberger, Christian;Reshef, Yakir A.;Finucane, Hilary K.;Schoenherr, Sebastian;Forer, Lukas;McCarthy, Shane;Abecasis, Goncalo R.;Durbin, Richard;Price, Alkes L.
通讯作者：
Price, Alkes L.
影响因子：
30.8
作者：
通讯作者：
--
影响因子：
64.8
作者：
Karczewski, Konrad J;Francioli, Laurent C;MacArthur, Daniel G
通讯作者：
MacArthur, Daniel G