Bayesian analysis of allelic penetrance models for complex binary traits

Abstract

a b s t r a c tComplex binary traits result from an intricate network of genetic and environmental factors. To aid their genetic dissection, several generalized linear models have been described to detect interaction between genes. However, it is recognized that these models have limited genetic interpretation. To overcome this problem, the allelic penetrance approach was proposed to model the action of a dominant or a recessive allele at a single locus, and to describe two-locus independent, inhibition, and cumulative actions. Classically, a recessive inheritance requires the expression of both recessive alleles in homozygotes to obtain the phenotype (type I recessiveness). In previous work, recessiveness was defined alternatively as a situation where a recessive allele is able to express the phenotype when the dominant allele is not active (type II recessiveness). Both definitions of recessiveness are then discussed under the allelic penetrance models.Bayesian methods are applied to analyze two data sets: one regarding the effect of the haplotype [HLA-B8, SC01, DR3] on the inheritance of IgD and IgG4 immunoglobulin deficiencies in humans, and other related to two-locus action in the control of Listeria infection susceptibility in mice.

Detecting gene–gene interactions that underlie human diseases

“…Although the extent to which biological interaction can be inferred from statistical interaction may be limited 102, some interesting recent work 107 108 109 has focussed on whether, given a strong prior biological model (or set of models), one can use genetic and/or genomic data from outbred populations or inbred strains, to assess model fit and compare the fit of competing models. This is, in a sense, a more modest goal in that it relies on some prior understanding (or at least a strong biological hypothesis) concerning the action of the relevant predictors.…”

Dynamics of Peripheral Regulatory and Effector T Cells Competing for Antigen Presenting Cells

“…This is particularly evident in the NOD mouse strain that spontaneously develops type I diabetes with incomplete penetrance in both males and females [43]. To explain this phenomenon, we and others have previously argued that a fraction of incomplete penetrance could be attributed to an internal stochastic component governing the expression of the phenotype, such as a stochastic allelic expression [44][45][46][47]. In the case of autoimmune diseases, we invoked the stochasticity in T cell repertoire generation as a putative explanation for this internal component of penetrance [45], following the observations in monozygotic twins when studying different autoimmune diseases [48,49].…”