Improving the Accuracy and Efficiency of Partitioning Heritability into the Contributions of Genomic Regions

Quantifying heritability, the amount of genetic contribution in a complex trait, has been of fundamental interest to geneticists for decades. Recently, partitioning the heritability accounted for by common variants into the contributions of genomic regions has received a lot of attention given its important applications for understanding the genetic architecture of complex traits. Current methods partition the total heritability by jointly estimating the contributions of all regions. However, these methods are computationally intractable and can be inaccurate when the number of regions is large. In this paper, we present an alternative approach that partitions the total heritability into the contributions of an arbitrary number of regions. We demonstrate by using simulations that our approach is more accurate and computationally efficient than current approaches. Using a data set from a genome-wide association study on human height, we demonstrate the utility of our method by estimating the heritability contributions of chromosomes and subchromosomal regions.