Models and estimation

The models implemented in Haplin are extensions of the log-linear models described and developed in the papers

  • Gjessing HK and Lie RT. Case-parent triads: Estimating single- and double-dose effects of fetal and maternal disease gene haplotypes. Annals of Human Genetics (2006) 70, pp. 382-396. Wilcox AJ, Weinberg CR, Lie RT (1998). Distinguishing the effects of maternal and offspring genes through studies of “case-parent triads”. American Journal of Epidemiology, 148(9): 893-901.
  • Weinberg CR, Wilcox AJ, Lie RT (1998). A log-linear approach to case-parent-triad data: assessing effects of disease genes that act directly or though maternal effects and that may be subject to parental imprinting. American Journal of Human Genetics, 62: 969-78.
and follow-ups to these. The basic log-linear model for case-parent triad data allows a user to compute relative risks associated with a variant allele, together with corresponding confidence intervals and p-values. It also allows a similar effect estimation for maternal alleles, i.e. to study the effect of genes of the mother that may influence the development of the fetus. Haplin extends these models to situations with multiple densely spaced SNPs (or other markers), where phase is unknown. Haplin then estimates the relative risks associated with haplotypes, not only single markers. In addition, Haplin uses a parametrization that will detect (at least with sufficient sample size) dominance- or recessive deviations from a dose-response model. For some details about parametrization, choice of reference category and interpretation of results, see parametrization.pdf. The most recent Haplin version also includes the option to run on case-control data, or to combine case-parent triads with control-parent triads.