A genome-wide association study of pulmonary tuberculosis in Morocco.
A genome-wide association study of pulmonary tuberculosis in Morocco.
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DOI：
10.1007/s00439-016-1633-2
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发表时间：
2016-03
期刊：
影响因子：
5.3
通讯作者：
Abel, L.
中科院分区：
文献类型：
--
作者：
Grant, A. V.;Sabri, A.;Abid, A.;Rhorfi, I. Abderrahmani;Benkirane, M.;Souhi, H.;Amrani, H. Naji;Alaoui-Tahiri, K.;Gharbaoui, Y.;Lazrak, F.;Sentissi, I.;Manessouri, M.;Belkheiri, S.;Zaid, S.;Bouraqadi, A.;El Amraoui, N.;Hakam, M.;Belkadi, A.;Orlova, M.;Boland, A.;Deswarte, C.;Amar, L.;Bustamante, J.;Boisson-Dupuis, S.;Casanova, J. L.;Schurr, E.;El Baghdadi, J.;Abel, L.
虽然流行病学证据表明肺结核（PTB）易感性的人类遗传基础，影响PTB风险的特定基因和等位基因的鉴定已被证明是困难的。以前的全基因组关联（GWA）研究只确定了三个新的基因座，在撒哈拉以南非洲和俄罗斯人群中具有适度的效应大小。我们在一个以家族为基础的发现摩洛哥样本中对550，352个常染色体SNP进行了GWA研究（在整个人群和<25岁的PTB诊断子集上），其中确定了143个SNP，p < 1 × 10−4。在独立的病例/对照样本中的重复研究鉴定了4个显示p < 0.01的SNP，其暗示相同的风险等位基因。在包括556名PTB受试者和650名对照的合并样本中，这四个SNP显示出暗示性关联（2 × 10−6 < p < 4 × 10−5）：rs358793和rs 17590261是基因间的，而rs6786408和rs 916943分别位于FOXP 1和AGMO的内含子中。这两种基因都参与巨噬细胞的功能，巨噬细胞是结核分枝杆菌潜伏和再活化的场所。最显著的发现（p = 2 × 10−6）是在早期（<25岁）发病年龄亚组中获得的AGMO SNP，证实了考虑发病年龄对解释PTB遗传基础的重要性。虽然只是提示性的，但这些发现为未来PTB的人类遗传学研究提供了几条途径。
Although epidemiological evidence suggests a human genetic basis of pulmonary tuberculosis (PTB) susceptibility, the identification of specific genes and alleles influencing PTB risk has proven to be difficult. Previous genome-wide association (GWA) studies have identified only three novel loci with modest effect sizes in sub-Saharan African and Russian populations. We performed a GWA study of 550,352 autosomal SNPs in a family-based discovery Moroccan sample (on the full population and on the subset with PTB diagnosis at <25 years), which identified 143 SNPs with p < 1 × 10−4. The replication study in an independent case/control sample identified four SNPs displaying a p < 0.01 implicating the same risk allele. In the combined sample including 556 PTB subjects and 650 controls these four SNPs showed suggestive association (2 × 10−6 < p < 4 × 10−5): rs358793 and rs17590261 were intergenic, while rs6786408 and rs916943 were located in introns of FOXP1 and AGMO, respectively. Both genes are involved in the function of macrophages, which are the site of latency and reactivation of Mycobacterium tuberculosis. The most significant finding (p = 2 × 10−6) was obtained for the AGMO SNP in an early (<25 years) age-at-onset subset, confirming the importance of considering age-at-onset to decipher the genetic basis of PTB. Although only suggestive, these findings highlight several avenues for future research in the human genetics of PTB.
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影响因子：
5.2
作者：
Horvath, S;Xu, X;Laird, NM
通讯作者：
Laird, NM
影响因子：
6.4
作者：
Cobat, Aurelie;Gallant, Caroline J.;Schurr, Erwin
通讯作者：
Schurr, Erwin
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
30.8
作者：
Curtis, James;Luo, Yang;Nejentsev, Sergey
通讯作者：
Nejentsev, Sergey
DOI：
10.1073/pnas.1115761109
发表时间：
2012-01-24
影响因子：
11.1
作者：
Barreiro, Luis B.;Tailleux, Ludovic;Gilad, Yoav
通讯作者：
Gilad, Yoav