Milet Jacqueline, Boland A., Luisi P., Sabbagh A., Sadissou I., Sonon P., Domingo N., Palstra F., Gineau L., Courtin David, Massougbodji A., Garcia André, Deleuze J. F., Perdry H. (2019). First genome-wide association study of non-severe malaria in two birth cohorts in Benin. Human Genetics, 138 (11-12), 1341-1357. ISSN 0340-6717.
Titre du document
First genome-wide association study of non-severe malaria in two birth cohorts in Benin
Année de publication
2019
Auteurs
Milet Jacqueline, Boland A., Luisi P., Sabbagh A., Sadissou I., Sonon P., Domingo N., Palstra F., Gineau L., Courtin David, Massougbodji A., Garcia André, Deleuze J. F., Perdry H.
Source
Human Genetics, 2019,
138 (11-12), 1341-1357 ISSN 0340-6717
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 x 10(-8) and p = 1.78 x 10(-7), respectively, in the discovery cohort). Strong statistical support was also found for a role of MYLK4 (meta-analysis, p = 5.29 x 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.
Plan de classement
Sciences fondamentales / Techniques d'analyse et de recherche [020]
;
Entomologie médicale / Parasitologie / Virologie [052]
Description Géographique
BENIN
Localisation
Fonds IRD [F B010077393]
Identifiant IRD
fdi:010077393
