Novel HLA associations with outcomes of Mycobacterium tuberculosis exposure and sarcoidosis in individuals of African ancestry using nearest-neighbor feature selection.
Novel HLA associations with outcomes of Mycobacterium tuberculosis exposure and sarcoidosis in individuals of African ancestry using nearest-neighbor feature selection.
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DOI：
10.1002/gepi.22490
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发表时间：
2022-10
影响因子：
2.1
通讯作者：
Montgomery, Courtney G.
中科院分区：
文献类型：
--
作者：
Dawkins, Bryan A.;Garman, Lori;Cejda, Nicholas;Pezant, Nathan;Rasmussen, Astrid;Rybicki, Benjamin A.;Levin, Albert M.;Benchek, Penelope;Seshadri, Chetan;Mayanja-Kizza, Harriet;Iannuzzi, Michael C.;Stein, Catherine M.;Montgomery, Courtney G.
关键词：
结核病和结节病是以肉芽肿为特征的炎性疾病，其可发生在任何器官，但通常在肺中发现。与这两种疾病的发生和/或严重程度相关的经典HLA等位基因的种类在不同研究中有很大差异。由于祖先和疾病亚表型等因素的变化，以及使用简单的建模策略来阐明可能的复杂关系，结果的异质性使得难以得出关于潜在共性的结论。在这里，我们在非洲血统的个体中进行HLA关联分析，使用更高的分辨率来包括疾病的亚表型，并采用更全面的分析技术。使用最近邻特征选择的新应用来对等位基因重要性进行评分，我们在对潜伏性结核分支杆菌感染和活动性疾病的首次分析中研究了HLA等位基因与结核分支杆菌暴露结果的相关性，与那些尽管长期暴露于活动性指示病例的人进行了比较，既没有阳性诊断测试，也没有表现出临床症状。我们还比较了持续性结节病和已消退结节病。这导致了新的HLA关联的识别以及主效应和相互作用效应的证据。我们发现在HLA-DRB 1、-DQB 1和-DPB 1对结核病（潜伏性或活动性）和持续性结节病耐药的患者中，主效应和交互效应惊人相似。
Tuberculosis and sarcoidosis are inflammatory diseases characterized by granulomas that may occur in any organ but are often found in the lung. The panoply of classical HLA alleles associated with occurrence and/or severity of both diseases varies considerably across studies. This heterogeneity of results, due to variation in factors like ancestry and disease sub-phenotype, as well as the use of simple modeling strategies to elucidate likely complex relationships, has made conclusions about underlying commonalities difficult. Here we perform HLA association analyses in individuals of African ancestry, using a greater resolution to include sub-phenotypes of disease and employing more comprehensive analytical techniques. Using a novel application of nearest-neighbor feature selection to score allelic importance, we investigated HLA allele association with Mycobacterium tuberculosis exposure outcomes in the first analysis of both latent Mycobacterium tuberculosis infection and active disease compared to those who, despite long term exposure to active index cases, have neither positive diagnostic tests nor display clinical symptoms. We also compared persistent to resolved sarcoidosis. This led to identification of novel HLA associations and evidence of main effects and interaction effects. We found strikingly similar main effects and interaction effects at HLA-DRB1, -DQB1, and -DPB1 in those resistant to tuberculosis (either latent or active) and persistent sarcoidosis.
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影响因子：
2.9
作者：
Levin AM;Adrianto I;Datta I;Iannuzzi MC;Trudeau S;McKeigue P;Montgomery CG;Rybicki BA
通讯作者：
Rybicki BA
影响因子：
24.3
作者：
Gupta, D.;Agarwal, R.;Jindal, S. K.
通讯作者：
Jindal, S. K.
影响因子：
5.8
作者：
Le, Trang T.;Simmons, W. Kyle;McKinney, Brett A.
通讯作者：
McKinney, Brett A.
通过替代变量分析捕获基因表达研究中的异质性。
影响因子：
4.5
作者：
Leek, Jeffrey T.;Storey, John D.
通讯作者：
Storey, John D.
非裔美国人1型糖尿病中的HLA II类基因关联揭示了保护性HLA-DRB1*03单倍型。
DOI：
10.1111/dme.12148
发表时间：
2013-06
期刊：
Diabetic medicine : a journal of the British Diabetic Association
影响因子：
--
作者：
Howson JM;Roy MS;Zeitels L;Stevens H;Todd JA
通讯作者：
Todd JA