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

Youssef Idaghdour, 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

Keywords

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

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Evidence for additive and interaction effects of host genotype and infection in malaria'. Together they form a unique fingerprint.

Cite this