Genetic analysis of variation in complex traits

Variation is a universal property of life, and much of contemporary genetics research is directed towards understanding the causes of variation in traits. Here I present the results of my investigations into the genetic and other causes of trait variation in humans and mice. I address these questions in the context of two distinct research projects, which use pre-existing data to investigate the causes of trait variation, through a range of analytic techniques. I first extract trait data from historic breeding records from the incipient Collaborative Cross (a genetic reference population of recombinant inbred mice) and use them to map genetic factors affecting litter size and other reproductive traits. Mapping reveals significant quantitative trait loci associated with litter size and time between litters, as well as a number of suggestive loci. I characterise the genetic effects at these loci and investigate candidate genes. The most robust finding, a litter size locus on chromosome 5, explains around 3% of observed variation and 24% of the variation attributable to genetics. Using data obtained from the Netherlands Twin Registry—a longitudinal database of Dutch twins—I investigate the prevalence of parent of origin effects on gene expression traits in peripheral blood in humans. I first phase individuals’ genotypes by parental origin and use these genotypes to calculate the heritability of over 44,000 gene expression traits partitioned into that attributable to matching and nonmatching parent of origin. I replicate prior genomewide heritability estimates for many traits, but I find little evidence of widespread parent-of-origin effects on human gene expression in blood. On further examination, the small sample size severely limits the power to detect such effects. Nonetheless, I identify approximately 200 genes enriched for immune system processes that show evidence of parent-of-origin-specific effects on heritability.