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Statistical genetic analysis of infectious disease (malaria) phenotypes from a longitudinal study in a population with significant familial relationships

Abstract : Long term longitudinal surveys have the advantage to enable several sampling of the studied phenomena and then, with the repeated measures obtained, find a confirmed tendency. However, these long term surveys generate large epidemiological datasets including more sources of noise than normal datasets (e.g. one single measure per observation unit) and potential correlation in the measured values. Here, we studied data from a long-term epidemiological and genetic survey of malaria disease in two family-based cohorts in Senegal, followed for 19 years (1990–2008) in Dielmo and for 16 years (1993–2008) in Ndiop. The main objectives of this work were to take into account familial relationships, repeated measures as well as effect of covariates to measure both environmental and host genetic (heritability) impacts on the outcome of infection with the malaria parasite Plasmodium falciparum, and then use findings from such analyses for linkage and association studies. The outcome of interest was the occurrence of a P. falciparum malaria attack during each trimester (PFA). The two villages were studied independently; epidemiological analyses, estimation of heritability and individual effects were then performed in each village separately. Linkage and association analyses used family-based methods (based on the original Transmission Disequilibrium Test) known to be immune from population stratification problems. Then to increase sample size for linkage and association analyses, data from the two villages were used together.
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Cheikh Loucoubar. Statistical genetic analysis of infectious disease (malaria) phenotypes from a longitudinal study in a population with significant familial relationships. General Mathematics [math.GM]. Université René Descartes - Paris V; Université Cheikh Anta Diop de Dakar, 2012. English. ⟨NNT : 2012PA05S003⟩. ⟨tel-00685104⟩

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