Genome-wide detection and characterization of mating asymmetry in human populations.

The study of the genetic component of early-onset diseases requires investigation into parental genetic effects, particularly those mediated by the mother who can influence the offspring's risk of disease through the effects of her genes acting directly on the intrauterine milieu or indirectly through maternal-gene child-gene interaction effects. An important source of bias that can arise in feto-maternal association testing is the possibility of confounding due to mating asymmetry (MA). However, there is little information on the levels of MA present in human populations and the impact on maternal association testing. In this study, we developed a novel approach to measuring MA and, using HapMap mate-pairs of European and African descent, carried out a genome-wide investigation and characterization of MA. We further investigated the impact of observed levels of MA on maternal association tests through simulation experiments. For the first time, we showed that non-negligible levels of MA are detected in human populations, such that subtle genotype frequency differences between individuals mating in the population are sufficient to induce spurious maternal genotype associations. Though the underlying mechanisms driving the asymmetry within these populations remain elusive, our findings provide consequential evidence for the occurrence of MA in humans and highlight the importance of controlling for MA in maternal association testing.

The heritability of glaucoma-related traits corneal hysteresis, central corneal thickness, intraocular pressure, and choroidal blood flow pulsatility.

PURPOSE: The purpose of this work was to investigate the heritability of potential glaucoma endophenotypes. We estimated for the first time the heritability of the pulsatility of choroidal blood flow. We also sought to confirm the heritability of corneal hysteresis, central corneal thickness, and 3 ways of measuring intraocular pressure. METHODS: Measurements were performed on 96 first-degree relatives recruited from Maisonneuve-Rosemont Hospital in Montreal. Corneal hysteresis was determined using the Reichert Ocular Response Analyser. Central corneal thickness was measured with an ultrasound pachymeter. Three measures of intraocular pressure were obtained: Goldmann-correlated and corneal compensated intraocular pressure using the Ocular Response Analyser, and Pascal intraocular pressure using the Pascal Dynamic Contour Tonometer. The pulsatility of choroidal blood velocity and flow were measured in the sub-foveolar choroid using single-point laser Doppler flowmetry (Oculix). We estimated heritability using maximum-likelihood variance components methods implemented in the SOLAR software. RESULTS: No significant heritability was detected for the pulsatility of choroidal blood flow or velocity. The Goldman-correlated, corneal compensated, and Pascal measures of intraocular pressure measures were all significantly heritable at 0.94, 0.79, and 0.53 after age and sex adjustment (p = 0.0003, p = 0.0023, p = 0.0239). Central corneal thickness was significantly heritable at 0.68 (p = 0.0078). Corneal hysteresis was highly heritable but the estimate was at the upper boundary of 1.00 preventing us from giving a precise estimate. CONCLUSION: Corneal hysteresis, central corneal thickness, and intraocular pressure are all heritable and may be suitable as glaucoma endophenotypes. The pulsatility of choroidal blood flow and blood velocity were not significantly heritable in this sample.