@article{fdi:010054205,
  title = {{I}mpact of changing drug treatment and malaria endemicity on the heritability of malaria phenotypes in a longitudinal family-based cohort study},
  author = {{L}oucoubar, {C}. and {G}oncalves, {B}. and {T}all, {A}. and {S}okhna, {C}heikh and {T}rape, {J}ean-{F}ran{\c{c}}ois and {S}arr, {F}. {D}. and {F}aye, {J}. and {B}adiane, {A}. and {L}y, {A}. {B}. and {D}iop, {A}. and {B}ar-{H}en, {A}. and {B}ureau, {J}. {F}. and {S}akuntabhai, {A}. and {P}aul, {R}.},
  editor = {},
  language = {{ENG}},
  abstract = {{D}espite considerable success of genome wide association ({GWA}) studies in identifying causal variants for many human diseases, their success in unraveling the genetic basis to complex diseases has been more mitigated. {P}athogen population structure may impact upon the infectious phenotype, especially with the intense short-term selective pressure that drug treatment exerts on pathogens. {R}igorous analysis that accounts for repeated measures and disentangles the influence of genetic and environmental factors must be performed. {A}ttempts should be made to consider whether pathogen diversity will impact upon host genetic responses to infection. {W}e analyzed the heritability of two {P}lasmodium falciparum phenotypes, the number of clinical malaria episodes ({PFA}) and the proportion of these episodes positive for gametocytes ({P}fgam), in a family-based cohort followed for 19 years, during which time there were four successive drug treatment regimes, with documented appearance of drug resistance. {R}epeated measures and variance components analyses were performed with fixed environmental, additive genetic, intra-individual and maternal effects for each drug period. {W}hilst there was a significant additive genetic effect underlying {PFA} during the first drug period of study, this was lost in subsequent periods. {T}here was no additive genetic effect for {P}fgam. {T}he intra-individual effect increased significantly in the chloroquine period. {T}he loss of an additive genetic effect following novel drug treatment may result in significant loss of power to detect genes in a {GWA} study. {P}rior genetic analysis must be a pre-requisite for more detailed {GWA} studies. {T}he temporal changes in the individual genetic and the intra-individual estimates are consistent with those expected if there were specific host-parasite interactions. {T}he complex basis to the human response to malaria parasite infection likely includes dominance/epistatic genetic effects encompassed within the intra-individual variance component. {E}valuating their role in influencing the outcome of infection through host genotype by parasite genotype interactions warrants research effort.},
  keywords = {},
  booktitle = {},
  journal = {{P}los {O}ne},
  volume = {6},
  numero = {11},
  pages = {e26364},
  ISSN = {1932-6203},
  year = {2011},
  DOI = {10.1371/journal.pone.0026364},
  URL = {https://www.documentation.ird.fr/hor/fdi:010054205},
}