A genome-wide association study of pulmonary tuberculosis in Morocco

A. V. Grant, A. Sabri, A. Abid, I. Abderrahmani Rhorfi, M. Benkirane, H. Souhi, H. Naji Amrani, K. Alaoui-Tahiri, Y. Gharbaoui, F. Lazrak, I. Sentissi, M. Manessouri, S. Belkheiri, S. Zaid, A. Bouraqadi, N. El Amraoui, M. Hakam, Abdelaziz Belkadi, M. Orlova, A. BolandC. Deswarte, L. Amar, J. Bustamante, S. Boisson-Dupuis, J. L. Casanova, E. Schurr, J. El Baghdadi, L. Abel

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)299-307
Number of pages9
JournalHuman Genetics
Volume135
Issue number3
DOIs
Publication statusPublished - 1 Mar 2016
Externally publishedYes

Fingerprint

Morocco
Genome-Wide Association Study
Pulmonary Tuberculosis
Single Nucleotide Polymorphism
Medical Genetics
Age of Onset
Alleles
Mycobacterium tuberculosis
Introns
Population
Genes
Macrophages

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Grant, A. V., Sabri, A., Abid, A., Abderrahmani Rhorfi, I., Benkirane, M., Souhi, H., ... Abel, L. (2016). A genome-wide association study of pulmonary tuberculosis in Morocco. Human Genetics, 135(3), 299-307. https://doi.org/10.1007/s00439-016-1633-2

A genome-wide association study of pulmonary tuberculosis in Morocco. / Grant, A. V.; Sabri, A.; Abid, A.; Abderrahmani Rhorfi, I.; Benkirane, M.; Souhi, H.; Naji Amrani, H.; Alaoui-Tahiri, K.; Gharbaoui, Y.; Lazrak, F.; Sentissi, I.; Manessouri, M.; Belkheiri, S.; Zaid, S.; Bouraqadi, A.; El Amraoui, N.; Hakam, M.; Belkadi, Abdelaziz; Orlova, M.; Boland, A.; Deswarte, C.; Amar, L.; Bustamante, J.; Boisson-Dupuis, S.; Casanova, J. L.; Schurr, E.; El Baghdadi, J.; Abel, L.

In: Human Genetics, Vol. 135, No. 3, 01.03.2016, p. 299-307.

Research output: Contribution to journalArticle

Grant, AV, Sabri, A, Abid, A, Abderrahmani Rhorfi, I, Benkirane, M, Souhi, H, Naji Amrani, H, 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, JL, Schurr, E, El Baghdadi, J & Abel, L 2016, 'A genome-wide association study of pulmonary tuberculosis in Morocco', Human Genetics, vol. 135, no. 3, pp. 299-307. https://doi.org/10.1007/s00439-016-1633-2
Grant AV, Sabri A, Abid A, Abderrahmani Rhorfi I, Benkirane M, Souhi H et al. A genome-wide association study of pulmonary tuberculosis in Morocco. Human Genetics. 2016 Mar 1;135(3):299-307. https://doi.org/10.1007/s00439-016-1633-2
Grant, A. V. ; Sabri, A. ; Abid, A. ; Abderrahmani Rhorfi, I. ; Benkirane, M. ; Souhi, H. ; Naji Amrani, H. ; Alaoui-Tahiri, K. ; Gharbaoui, Y. ; Lazrak, F. ; Sentissi, I. ; Manessouri, M. ; Belkheiri, S. ; Zaid, S. ; Bouraqadi, A. ; El Amraoui, N. ; Hakam, M. ; Belkadi, Abdelaziz ; Orlova, M. ; Boland, A. ; Deswarte, C. ; Amar, L. ; Bustamante, J. ; Boisson-Dupuis, S. ; Casanova, J. L. ; Schurr, E. ; El Baghdadi, J. ; Abel, L. / A genome-wide association study of pulmonary tuberculosis in Morocco. In: Human Genetics. 2016 ; Vol. 135, No. 3. pp. 299-307.
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abstract = "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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AU - Grant, A. V.

AU - Sabri, A.

AU - Abid, A.

AU - Abderrahmani Rhorfi, I.

AU - Benkirane, M.

AU - Souhi, H.

AU - Naji Amrani, H.

AU - Alaoui-Tahiri, K.

AU - Gharbaoui, Y.

AU - Lazrak, F.

AU - Sentissi, I.

AU - Manessouri, M.

AU - Belkheiri, S.

AU - Zaid, S.

AU - Bouraqadi, A.

AU - El Amraoui, N.

AU - Hakam, M.

AU - Belkadi, Abdelaziz

AU - Orlova, M.

AU - Boland, A.

AU - Deswarte, C.

AU - Amar, L.

AU - Bustamante, J.

AU - Boisson-Dupuis, S.

AU - Casanova, J. L.

AU - Schurr, E.

AU - El Baghdadi, J.

AU - Abel, L.

PY - 2016/3/1

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