Evidence for additive and interaction effects of host genotype and infection in malaria

Youssef Idaghdhour, Jacklyn Quinlan, Jean Philippe Goulet, Joanne Berghout, Elias Gbeha, Vanessa Bruat, Thibault De Malliard, Jean Christophe Grenier, Selma Gomez, Philippe Gros, Mohamed Cheŕif Rahimy, Ambaliou Sanni, Philip Awadalla

    Research output: Contribution to journalArticle

    Abstract

    The host mechanisms responsible for protection against malaria remain poorly understood, with only a few protective genetic effects mapped in humans. Here, we characterize a host-specific genome-wide signature in whole-blood transcriptomes of Plasmodium falciparum-infected West African children and report a demonstration of genotype-by-infection interactions in vivo. Several associations involve transcripts sensitive to infection and implicate complement system, antigen processing and presentation, and T-cell activation (i.e., SLC39A8, C3AR1, FCGR3B, RAD21, RETN, LRRC25, SLC3A2, and TAPBP), including one association that validated a genome-wide association candidate gene (SCO1), implicating binding variation within a noncoding regulatory element. Gene expression profiles in mice infected with Plasmodium chabaudi revealed and validated similar responses and highlighted specific pathways and genes that are likely important responders in both hosts. These results suggest that host variation and its interplay with infection affect children's ability to cope with infection and suggest a polygenic model mounted at the transcriptional level for susceptibility.

    Original languageEnglish (US)
    Pages (from-to)16786-16793
    Number of pages8
    JournalProceedings of the National Academy of Sciences of the United States of America
    Volume109
    Issue number42
    DOIs
    StatePublished - Oct 16 2012

    Fingerprint

    Malaria
    Genotype
    Antigen Presentation
    Infection
    Transcriptome
    Plasmodium chabaudi
    Genome
    Plasmodium falciparum
    Genes
    T-Lymphocytes

    Keywords

    • EQTL
    • ESNP
    • Genotype-by-environment interactions
    • Host response
    • Parasite load

    ASJC Scopus subject areas

    • General

    Cite this

    Evidence for additive and interaction effects of host genotype and infection in malaria. / Idaghdhour, Youssef; Quinlan, Jacklyn; Goulet, Jean Philippe; Berghout, Joanne; Gbeha, Elias; Bruat, Vanessa; De Malliard, Thibault; Grenier, Jean Christophe; Gomez, Selma; Gros, Philippe; Rahimy, Mohamed Cheŕif; Sanni, Ambaliou; Awadalla, Philip.

    In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 109, No. 42, 16.10.2012, p. 16786-16793.

    Research output: Contribution to journalArticle

    Idaghdhour, Y, Quinlan, J, Goulet, JP, Berghout, J, Gbeha, E, Bruat, V, De Malliard, T, Grenier, JC, Gomez, S, Gros, P, Rahimy, MC, Sanni, A & Awadalla, P 2012, 'Evidence for additive and interaction effects of host genotype and infection in malaria', Proceedings of the National Academy of Sciences of the United States of America, vol. 109, no. 42, pp. 16786-16793. https://doi.org/10.1073/pnas.1204945109
    Idaghdhour, Youssef ; Quinlan, Jacklyn ; Goulet, Jean Philippe ; Berghout, Joanne ; Gbeha, Elias ; Bruat, Vanessa ; De Malliard, Thibault ; Grenier, Jean Christophe ; Gomez, Selma ; Gros, Philippe ; Rahimy, Mohamed Cheŕif ; Sanni, Ambaliou ; Awadalla, Philip. / Evidence for additive and interaction effects of host genotype and infection in malaria. In: Proceedings of the National Academy of Sciences of the United States of America. 2012 ; Vol. 109, No. 42. pp. 16786-16793.
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