Biology subjects

Damena, D.

Publications and source records attributed to Damena, D..

2 recordsLinked to original sources

bioRxiv2019

Genome-wide heritability analysis of severe malaria susceptibility and resistance reveals evidence of polygenic inheritance

ObjectiveEstimating SNP-heritability (h2g) of severe malaria/resistance and its distribution across the genome might shed new light in to the underlying biology.\n\nMethodWe investigated h2g of severe malaria susceptibility and resistance from genome-wide association study (GWAS) dataset (sample size =11, 657). We partitioned the h2g in to chromosomes, allele frequencies and annotations. We further examined none-cell type specific and cell type specific enrichments from GWAS-summary statistics.\n\nResultsWe estimated the h2g of severe malaria at 0.21 (se=0.05, p=2.7x10-5), 0.20 (se =0.05, p=7.5x10-5) and 0.17 (se =0.05, p= 7.2x10-4) in Gambian, Kenyan and Malawi populations, respectively. The h2g attributed to the GWAS significant SNPs and the well-known sickle cell (HbS) variant was approximately 0.07 and 0.03, respectively. We prepared African population reference panel and obtained comparable h2g estimate (0.21 (se = 0.02, p< 1x10-5)) from GWAS-summary statistics meta-analysed across the three populations. Partitioning analysis from raw genotype data showed significant enrichment of h2g in protein coding genic SNPs while summary statistics analysis suggests pattern of enrichment in multiple categories.\n\nConclusionWe report for the first time that the heritability of malaria susceptibility and resistance is largely ascribed by common SNPs and the causal variants are overrepresented in protein coding regions of the genome. Overall, our results suggest that malaria susceptibility and resistance is a polygenic trait. Further studies with larger sample sizes are needed to better understand the underpinning genetics of resistance and susceptibility to severe malaria.

bioinformatics↗

bioRxiv2018

Genome-Wide Association Studies of malaria susceptibility and resistance: progress, pitfalls and prospects

P. falciparum malaria is still among the leading causes of child mortality in sub-Saharan Africa; killing hundreds of thousands of children each year. Malaria has been recognized as one of the prominent evolutionary selective forces of human genome that led to the emergence of multiple host protective polymorphisms associated with minimizing the risk of developing severe malaria in endemic areas. A comprehensive understanding of the genetic bases of malaria resistance can shed light to the molecular mechanisms of host-parasite interactions that can potentially pave ways to the development of new therapeutics and vaccines. Genome-wide association studies (GWASs) have recently been implemented in malaria endemic areas and identified a number of novel association genetic variants. Despite this success, only few variants did replicate across the studies and the underlying biology is yet to be understood for the majority of the novel variants. Besides, there are several open questions around heritability, polygenic effects, epistatic interactions, genetic correlations and associated molecular pathways among others. In this review, we first assess the progress and pitfalls of malaria susceptibility GWASs. We then, provide an overview of the current progress in post-GWAS approaches and discuss how these approaches can potentially be implemented in malaria susceptibility GWASs to extract further functional information. We conclude by highlighting the importance of multi-step and multidimensional integrative studies for unravelling the genetic basis of malaria susceptibility and resistance at systems biology level.

genomics↗