Complex Traits and Candidate Genes: Estimation of Genetic Variance Components Across Modes of Inheritance

Abstract

Large-effect loci--those discovered by genome-wide association studies or linkage mapping--associated with key traits segregate amidst a background of minor, often undetectable genetic effects in both wild and domesticated plants and animals. Accurately attributing mean differences and variance explained to the correct components in the linear mixed model (LMM) analysis is important for both selecting superior progeny and parents in plant and animal breeding, but also for gene therapy and medical genetics in humans. Marker-assisted prediction (MAP) and its successor, genomic prediction (GP), have many advantages for selecting superior individuals and understanding disease risk. However, these two approaches are less often integrated to simultaneously study the modes of inheritance of complex traits. This simulation study demonstrates that the average semivariance can be applied to models incorporating Mendelian, oligogenic, and polygenic terms, simultaneously, and yields accurate estimates of the variance explained for all relevant terms. Our previous research focused on large-effect loci and polygenic variance exclusively, and in this work we want to synthesize and expand the average semivariance framework to a multitude of different genetic architectures and the corresponding mixed models. This framework independently accounts for the effects of large-effect loci and the polygenic genetic background and is universally applicable to genetics studies in humans, plants, animals, and microbes.