The v-MFG test: Investigating maternal, offspring and maternal-fetal genetic incompatibility effects on disease and viability

The MFG test is a family-based association test that detects genetic effects contributing to disease in offspring, including offspring allelic effects, maternal allelic effects and MFG incompatibility effects. Like many other family-based association tests, it assumes that the offspring survival and the offspring-parent genotypes are conditionally independent provided the offspring is affected. However, when the putative disease-increasing locus can affect another competing phenotype, for example, offspring viability, the conditional independence assumption fails and these tests could lead to incorrect conclusions regarding the role of the gene in disease. We propose the v-MFG test to adjust for the genetic effects on one phenotype, e.g., viability, when testing the effects of that locus on another phenotype, e.g., disease. Using genotype data from nuclear families containing parents and at least one affected offspring, the v-MFG test models the distribution of family genotypes conditional on offspring phenotypes. It simultaneously estimates genetic effects on two phenotypes, viability and disease. Simulations show that the v-MFG test produces accurate genetic effect estimates on disease as well as on viability under several different scenarios. It generates accurate type-I error rates and provides adequate power with moderate sample sizes to detect genetic effects on disease risk when viability is reduced. We demonstrate the v-MFG test with HLA-DRB1 data from study participants with rheumatoid arthritis (RA) and their parents, we show that the v-MFG test successfully detects an MFG incompatibility effect on RA while simultaneously adjusting for a possible viability loss.

Mental playmates: Siblings, executive functioning and theory of mind

This study assessed the theory of mind (ToM) and executive functioning (EF) abilities of 124 typically developing preschool children aged 3 to 5 years in relation to whether or not they had a child-aged sibling (i.e. a child aged 1 to 12 years) at home with whom to play and converse. On a ToM battery that included tests of false belief, appearance-reality (AR) and pretend representation, children who had at least 1 child-aged sibling scored significantly higher than both only children and those whose only siblings were infants or adults. The numbers of child-aged siblings in preschoolers' families positively predicted their scores on both a ToM battery (4 tasks) and an EF battery (2 tasks), and these associations remained significant with language ability partialled out. Results of a hierarchical multiple regression analysis revealed that independent contributions to individual differences in ToM were made by language ability, EF skill and having a child-aged sibling. However, even though some conditions for mediation were met, there was no statistically reliable evidence that EF skills mediated the advantage of presence of child-aged siblings for ToM performance. While consistent with the theory that distinctively childish interaction among siblings accelerates the growth of both TOM and EF capacities, alternative evidence and alternative theoretical interpretations for the findings were also considered.