@article{fdi:010069947,
  title = {{D}etecting multi-way epistasis in family-based association studies},
  author = {{L}oucoubar, {C}. and {G}rant, {A}. {V}. and {B}ureau, {J}. {F}. and {C}asademont, {I}. and {B}ar, {N}. {A}. and {B}ar-{H}en, {A}. and {D}iop, {M}. and {F}aye, {J}. and {S}arr, {F}. {D}. and {B}adiane, {A}. and {T}all, {A}. and {T}rape, {J}ean-{F}ran{\c{c}}ois and {C}liquet, {F}. and {S}chwikowski, {B}. and {L}athrop, {M}. and {P}aul, {R}. {E}. and {S}akuntabhai, {A}.},
  editor = {},
  language = {{ENG}},
  abstract = {{T}he era of genome-wide association studies ({GWAS}) has led to the discovery of numerous genetic variants associated with disease. {B}etter understanding of whether these or other variants interact leading to differential risk compared with individual marker effects will increase our understanding of the genetic architecture of disease, which may be investigated using the family-based study design. {W}e present {M}-{TDT} (the multi-locus transmission disequilibrium test), a tool for detecting family-based multi-locus multi-allelic effects for qualitative or quantitative traits, extended from the original transmission disequilibrium test ({TDT}). {T}ests to handle the comparison between additive and epistatic models, lack of independence between markers and multiple offspring are described. {P}erformance of {M}-{TDT} is compared with a multifactor dimensionality reduction ({MDR}) approach designed for investigating families in the hypothesis-free genome-wide setting (the multifactor dimensionality reduction pedigree disequilibrium test, {MDR}-{PDT}). {O}ther methods derived from the {TDT} or {MDR} to investigate genetic interaction in the family-based design are also discussed. {T}he case of three independent biallelic loci is illustrated using simulations for one-to three-locus alternative hypotheses. {M}-{TDT} identified joint-locus effects and distinguished effectively between additive and epistatic models. {W}e showed a practical example of {M}-{TDT} based on three genes already known to be implicated in malaria susceptibility. {O}ur findings demonstrate the value of {M}-{TDT} in a hypothesis-driven context to test for multi-way epistasis underlying common disease etiology, whereas {MDR}-{PDT}-based methods are more appropriate in a hypothesis-free genome-wide setting.},
  keywords = {family-based genetic association studies ; multi-locus ; epistasis ; interaction ; malaria ; innate immunity},
  booktitle = {},
  journal = {{B}riefings in {B}ioinformatics},
  volume = {18},
  numero = {3},
  pages = {394--402},
  ISSN = {1467-5463},
  year = {2017},
  DOI = {10.1093/bib/bbw039},
  URL = {https://www.documentation.ird.fr/hor/fdi:010069947},
}