First genome-wide association study of non-severe malaria in two birth cohorts in Benin

AbstractRecent 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 p ositional, eQTL, and chromatin interaction mapping to identify the genes underlying association signals. Our study highlights a role ofPTPRT, a tyrosine phosphatase receptor involved in STAT3 pathway, in the protection against both mild malaria attacks and malaria infections (p = 9.70 × 10−8 andp = 1.78 × 10−7, respectively, in the discovery cohort). Strong statistical support was also found for a role ofMYLK4 (meta-analysis,p = 5.29 × 10−8 with malaria attacks), and forseveral 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 underlyin...
Source: Human Genetics - Category: Genetics & Stem Cells Source Type: research