A common molecular signature of patients with sickle cell disease revealed by microarray meta-analysis and a genome-wide association study

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dc.contributor.authorHamda, Cherif B
dc.contributor.authorSangeda, Raphael
dc.contributor.authorMwita, Liberata
dc.contributor.authorMeintjes, Ayton
dc.contributor.authorNkya, Siana
dc.contributor.authorPanji, Sumir
dc.contributor.authorMulder, Nicola
dc.contributor.authorGuizani-Tabbane, Lamia
dc.contributor.authorBenkahla, Alia
dc.contributor.authorMakani, Julie
dc.contributor.authorGhedira, Kais
dc.date.accessioned2019-05-07T16:35:24Z
dc.date.available2019-05-07T16:35:24Z
dc.date.issued2018
dc.description.abstractA chronic inflammatory state to a large extent explains sickle cell disease (SCD) pathophysiology. Nonetheless, the principal dysregulated factors affecting this major pathway and their mechanisms of action still have to be fully identified and elucidated. Integrating gene expression and genome-wide association study (GWAS) data analysis represents a novel approach to refining the identification of key mediators and functions in complex diseases. Here, we performed gene expression meta-analysis of five independent publicly available microarray datasets related to homozygous SS patients with SCD to identify a consensus SCD transcriptomic profile. The meta-analysis conducted using the MetaDE R package based on combining p values (maxP approach) identified 335 differentially expressed genes (DEGs; 224 upregulated and 111 downregulated). Functional gene set enrichment revealed the importance of several metabolic pathways, of innate immune responses, erythrocyte development, and hemostasis pathways. Advanced analyses of GWAS data generated within the framework of this study by means of the atSNP R package and SIFT tool identified 60 regulatory single-nucleotide polymorphisms (rSNPs) occurring in the promoter of 20 DEGs and a deleterious SNP, affecting CAMKK2 protein function. This novel database of candidate genes, transcription factors, and rSNPs associated with SCD provides new markers that may help to identify new therapeutic targets.en_US
dc.identifier.doihttps://doi.org/10.1371/journal.pone.0199461
dc.identifier.urihttp://hdl.handle.net/20.500.11810/5233
dc.language.isoenen_US
dc.publisherPLoS ONEen_US
dc.titleA common molecular signature of patients with sickle cell disease revealed by microarray meta-analysis and a genome-wide association studyen_US
dc.typeJournal Articleen_US
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