45 - Partitioning SNP Heritability in Related Individuals

Partitioning SNP heritability by many functional annotations has been a successful tool for understanding the genetic architecture of complex traits in human genetic studies. Similar analyses are being extended to animal research, as (imputed) whole-genome sequence data of many individuals and various functional annotations have become available in livestock animals. Though many approaches have been developed for heritability partition (e.g., LDSC and HE-reg), they are mostly based on approximations tailored to human populations and few can produce statistically efficient estimates for animal genomic studies where individuals are often related. To tackle this issue, we present a stochastic MINQUE (Minimum Norm Quadratic Unbiased Estimation) approach for partitioning SNP heritability, which we refer to as MPH. We provide a theoretical analysis comparing LDSC and HE-reg with REML and MPH and demonstrate what LDSC and HE-reg (and similar methods) take advantage of in their approximations: sparse relationships between individuals and relatively weak linkage disequilibrium. We also show that our method is mathematically equivalent to the MC-REML approach implemented in BOLT. MPH has three key features. First, it is comparable to genomic REML in terms of accuracy, while being at least one order of magnitude faster than GCTA and BOLT and using only ~1/4 of memory as much as GCTA, when applied to sequence data and many variance components (or functional annotation categories). Second, it can do weighted analyses if residual variances are unequal (such as DYD). Third, it works for many overlapping functional annotations. Using simulations based on a human pedigree and a dairy cattle pedigree, we illustrate the benefits of our method for partitioning SNP heritability in pedigree-based studies. We also demonstrate that it is feasible to efficiently partition SNP heritability for animal genomes with strong, long-span LD. MPH is freely available at https://jiang18.github.io/mph.