Multi-ancestry meta-analysis of host genetic susceptibility to tuberculosis identifies shared genetic architecture.
Multi-ancestry meta-analysis of host genetic susceptibility to tuberculosis identifies shared genetic architecture.
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DOI：
10.7554/elife.84394
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发表时间：
2024-01-15
期刊：
影响因子：
7.7
通讯作者：
International Tuberculosis Host Genetics Consortium
中科院分区：
文献类型：
--
作者：
Schurz H;Naranbhai V;Yates TA;Gilchrist JJ;Parks T;Dodd PJ;Möller M;Hoal EG;Morris AP;Hill AVS;International Tuberculosis Host Genetics Consortium
结核病易感性的遗传性已得到广泛认可。已经研究了100多个基因作为结核病易感性的候选基因，并且通过全基因组关联研究（GWAS）鉴定了几种变体，但是很少有重复的。我们建立了国际结核病宿主遗传学联盟，对GWAS进行多血统荟萃分析，包括非洲、亚洲和欧洲血统的14，153例病例和19，536例对照。我们的分析表明，对结核病的易感性具有很大程度的遗传性（合并多基因h2 = 26.3%，95%CI 23.7-29.0%），这是跨祖先共享的，突出了对疾病的重要宿主遗传影响。我们在人类白细胞抗原（HLA）-II区域（rs 28383206，p值=5.2 × 10-9）中确定了一个具有全基因组显著性（p<5 × 10-8）的结核病全球宿主遗传相关性，但未能复制先前与结核病易感性相关的变异。这些数据表明了结核病易感性的复杂的共享遗传结构，以及在经历不同感染压力水平的多个祖先中进行大规模GWAS分析的重要性。
The heritability of susceptibility to tuberculosis (TB) disease has been well recognized. Over 100 genes have been studied as candidates for TB susceptibility, and several variants were identified by genome-wide association studies (GWAS), but few replicate. We established the International Tuberculosis Host Genetics Consortium to perform a multi-ancestry meta-analysis of GWAS, including 14,153 cases and 19,536 controls of African, Asian, and European ancestry. Our analyses demonstrate a substantial degree of heritability (pooled polygenic h2 = 26.3%, 95% CI 23.7–29.0%) for susceptibility to TB that is shared across ancestries, highlighting an important host genetic influence on disease. We identified one global host genetic correlate for TB at genome-wide significance (p<5 × 10-8) in the human leukocyte antigen (HLA)-II region (rs28383206, p-value=5.2 × 10-9) but failed to replicate variants previously associated with TB susceptibility. These data demonstrate the complex shared genetic architecture of susceptibility to TB and the importance of large-scale GWAS analysis across multiple ancestries experiencing different levels of infection pressure.
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影响因子：
4.5
作者：
Quistrebert J;Orlova M;Kerner G;Ton LT;Luong NT;Danh NT;Vincent QB;Jabot-Hanin F;Seeleuthner Y;Bustamante J;Boisson-Dupuis S;Huong NT;Ba NN;Casanova JL;Delacourt C;Hoal EG;Alcaïs A;Thai VH;Thành LT;Abel L;Schurr E;Cobat A
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Cobat A
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通讯作者：
Abel, L.
影响因子：
2.1
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.
通讯作者：
Montgomery, Courtney G.
影响因子：
2.1
作者：
Stein CM;Sausville L;Wejse C;Sobota RS;Zetola NM;Hill PC;Boom WH;Scott WK;Sirugo G;Williams SM
通讯作者：
Williams SM