Academic Journal
First genome-wide association study of non-severe malaria in two birth cohorts in Benin
| العنوان: | First genome-wide association study of non-severe malaria in two birth cohorts in Benin |
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| المؤلفون: | Milet, Jacqueline, Boland, Anne, Luisi, Pierre, Sabbagh, Audrey, Sadissou, Ibrahim, Sonon, Paulin, Domingo, Nadia, Palstra, Friso, Gineau, Laure, Courtin, David, Massougbodji, Achille, Garcia, André, Deleuze, Jean-François, Perdry, Hervé |
| المساهمون: | Mère et enfant en milieu tropical : pathogènes, système de santé et transition épidémiologique (MERIT - UMR_D 216), Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5), Centre National de Recherche en Génomique Humaine (CNRGH), Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Consejo Nacional de Investigaciones Científicas y Técnicas Buenos Aires (CONICET), Universidade de São Paulo = University of São Paulo (USP), Centre d’Etude et de Recherche sur le Paludisme Associé à la Grossesse et l’Enfance Cotonou, Bénin (CERPAGE), Université d’Abomey-Calavi = University of Abomey Calavi (UAC), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), French ministry of Research and Technology (REFS Nu2006-22), Institut de Recherche pour le Développement (IRD), ANR-SEST-2006-0040 |
| المصدر: | ISSN: 1432-1203 ; Hum Genet ; https://cea.hal.science/cea-04457191 ; Hum Genet, 2019, 138 (11-12), pp.1341-1357. ⟨10.1007/s00439-019-02079-5⟩ ; https://link.springer.com/article/10.1007/s00439-019-02079-5. |
| بيانات النشر: | HAL CCSD |
| سنة النشر: | 2019 |
| المجموعة: | Université de Versailles Saint-Quentin-en-Yvelines: HAL-UVSQ |
| مصطلحات موضوعية: | [SDV.GEN]Life Sciences [q-bio]/Genetics, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN] |
| الوصف: | International audience ; Recent research efforts to identify genes involved in malaria susceptibility using genome-wide approaches have focused on severe malaria. Here, we present the first GWAS on non-severe malaria designed to identify genetic variants involved in innate immunity or innate resistance mechanisms. Our study was performed on two cohorts of infants from southern Benin (525 and 250 individuals used as discovery and replication cohorts, respectively) closely followed from birth to 18–24 months of age, with an assessment of a space- and time-dependent environmental risk of exposure. Both the recurrence of mild malaria attacks and the recurrence of malaria infections as a whole (symptomatic and asymptomatic) were considered. Post-GWAS functional analyses were performed using positional, eQTL, and chromatin interaction mapping to identify the genes underlying association signals. Our study highlights a role of PTPRT, a tyrosine phosphatase receptor involved in STAT3 pathway, in the protection against both mild malaria attacks and malaria infections (p = 9.70 × 10−8 and p = 1.78 × 10−7, respectively, in the discovery cohort). Strong statistical support was also found for a role of MYLK4 (meta-analysis, p = 5.29 × 10−8 with malaria attacks), and for several other genes, whose biological functions are relevant in malaria infection. Results shows that GWAS on non-severe malaria can successfully identify new candidate genes and inform physiological mechanisms underlying natural protection against malaria. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | BIORXIV: 483859; IRD: fdi:010077393 |
| DOI: | 10.1007/s00439-019-02079-5 |
| الاتاحة: | https://cea.hal.science/cea-04457191 https://cea.hal.science/cea-04457191v1/document https://cea.hal.science/cea-04457191v1/file/483859.full.pdf https://doi.org/10.1007/s00439-019-02079-5 |
| Rights: | info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.A82B2DD5 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1007/s00439-019-02079-5 |
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