Missing heritability may be explained by the common household environment and its interaction with genetic variation

2018-12-07The 'missing heritability' problem describes the fact that the explained heritability from identified genetic variation associated with phenotypes/diseases is much smaller than the estimated total heritability from traditional population studies. ❧ This dissertation proposed a hypothesis to explain the missing heritability problem. We claimed that the problem may be due to the inflated estimation of the total heritability from population studies with misspecified model. We used theoretical derivation and simulations to illustrate that the heritability would be overestimated when there was common household environment (CHE) and/or its interaction with genetic variation but was not specified in the estimation model. We then proposed a method based on linear mixed-effects model (LMM) to properly account for the CHE and the interaction, which could be used to estimate the heritability without bias. The connection between this method and standard LMM methods was also built. We further proposed hypothesis testing frameworks for model selection. Finally we tested both the estimation and hypothesis testing methods using the Framingham Heart Study data, and found evidence supporting the hypothesis of this dissertation on the source of missing heritability