Using Haplotype Mapping to Uncover the Missing Heritability: A Simulation Study

Abstract Text:

An improved regional mapping method is proposed based on haplotype information with haplotype blocks being used as analysis regions. Genomic data were simulated using circa 300K SNPs. The simulated phenotypes’ heritability was 0.30 from which 0.05 was regional heritability. Twenty different regions of genome were selected to be trait associated in the simulation. Four scenarios were used to generate regional variance with either one SNP, all SNPs, one haplotype or all haplotypes from the region being the causal variants. Regional genomic relationship matrices constructed with SNP-based or haplotype-based methods were used in a REML framework to estimate the variance explained by the region. Our results show that the proposed haplotype-based method always captures the effect of the regions, albeit with decreased performance with increasing block size in SNP-based variants. SNP-based methods often do not detect the effect of causal haplotype(s).

Keywords:

missing heritability

regional mapping method

haplotype blocks