从欧洲和非洲裔美国哮喘患者中鉴定出四个新的基因位点
2016/11/09
摘要
基本原理：尽管我们对哮喘遗传结构的认知有了显著的进步，但在人群之间的变异压力的影响仍然有待研究发现。
目的：确定欧洲裔和非裔美国人哮喘的附加遗传易感因素
方法：开发了一个表型的算法从电子医疗记录和基因组学（eMERGE）网络来挖掘电子病历和验证招募的哮喘病例和对照。在从欧洲和非洲血统的美国儿童和成人哮喘病例中分析全基因组关联，随后进行荟萃分析（meta-analysis）。名义上显著的结果考虑到过敏状态进行了重新分析。
主要的结果：对该算法的验证得到了病例和对照平均95.8%正的预测值。该算法累计获得了21644个病例（65.83%的欧洲裔美国人和34.17%的非洲裔美国人）。经过Meta分析，我们确定了四个新的与哮喘相关的人口特异位点：欧洲裔美国人中的位点6p21.31、9p21.2和10q21.3，非裔美国人的PTGES基因。9p21.2的TEK，编码TIE2，已被证明参与哮喘气道壁重塑，考虑到过敏因素之后，它们之间的关联依然显著。PTGES，它编码的前列腺素E合成酶，也与哮喘有关，前列腺素E2的合成缺乏与气道重塑有关。
结论：这项研究增加了我们对欧洲裔美国人和非裔美国人哮喘的遗传结构的理解，并有必要加强研究不同种族背景的人群，以确定哮喘共同的和独特的遗传预测因子。
关键词：哮喘；GWAS；遗传
（杨冬 审校）
Am J Respir Crit Care Med. 2016 Sep 9. [Epub ahead of print]
Identification of Four Novel Loci in Asthma in European and African American Populations.
Almoguera B1, Vazquez L2, Mentch F3, Connolly J4, Pacheco JA5, Sundaresan AS6, Peissig PL7, Linneman JG8, McCarty CA9, Crosslin D10, Carrell DS11, Lingren T12, Namjou-Khales B13, Harley JB14,15, Larson E16, Jarvik GP17, Brilliant M18, Williams MS19, Kullo IJ20, Hysinger EB21, Sleiman PM22, Hakonarson H23.
Author information
Abstract
RATIONALE:Despite significant advances in our knowledge of the genetic architecture of asthma, specific contributors to the variability in the burden between populations remain uncovered.
OBJECTIVE:To identify additional genetic susceptibility factors of asthma in European American and African American populations.
METHODS:A phenotyping algorithm mining Electronic Medical Records was developed and validated to recruit cases with asthma and controls from the eMERGE (electronic Medical Records and Genomics) network. Genome-wide association analyses were performed in pediatric and adultasthma cases and controls from European and African American ancestry followed by meta-analysis. Nominally significant results were re-analyzed conditioning on allergy status.
MAIN RESULTS:The validation of the algorithm yielded an average of 95.8% positive predictive values for both cases and controls. The algorithm accrued 21,644 subjects (65.83% European American and 34.17% African American). We identified four novel population-specific associations with asthma after meta-analyses: loci 6p21.31, 9p21.2 and 10q21.3 in the European American population and the PTGES gene in African Americans. TEK at 9p21.2, which encodes TIE2, has been shown to be involved in remodeling the airway wall in asthma and the association remained significant after conditioning by allergy. PTGES, which encodes the prostaglandin E synthase, has also been linked to asthma, where deficient prostaglandin E2 synthesis has been associated with airway remodeling.
CONCLUSION:This study adds to our understanding of the genetic architecture of asthma in European Americans and African Americans and reinforces the need to study populations of diverse ethnic backgrounds to identify shared and unique genetic predictors of asthma.
KEYWORDS:Asthma; GWAS; Genetics
Am J Respir Crit Care Med. 2016 Sep 9. [Epub ahead of print]
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