Comparison of the Accuracy of Epistasis and Haplotype Models for Genomic Prediction of Seven Human Phenotypes

Zuoxiang Liang, Dzianis Prakapenka, Yang Da

Research output: Contribution to journalArticlepeer-review


The accuracy of predicting seven human phenotypes of 3657–7564 individuals using global epistasis effects was evaluated and compared to the accuracy of haplotype genomic prediction using 380,705 SNPs and 10-fold cross-validation studies. The seven human phenotypes were the normality transformed high density lipoproteins (HDL), low density lipoproteins (LDL), total cholesterol (TC), triglycerides (TG), weight (WT), and the original phenotypic observations of height (HTo) and body mass index (BMIo). Fourth-order epistasis effects virtually had no contribution to the phenotypic variances, and third-order epistasis effects did not affect the prediction accuracy. Without haplotype effects in the prediction model, pairwise epistasis effects improved the prediction accuracy over the SNP models for six traits, with accuracy increases of 2.41%, 3.85%, 0.70%, 0.97%, 0.62% and 0.93% for HDL, LDL, TC, HTo, WT and BMIo respectively. However, none of the epistasis models had higher prediction accuracy than the haplotype models we previously reported. The epistasis model for TG decreased the prediction accuracy by 2.35% relative to the accuracy of the SNP model. The integrated models with epistasis and haplotype effects had slightly higher prediction accuracy than the haplotype models for two traits, HDL and BMIo. These two traits were the only traits where additive × dominance effects increased the prediction accuracy. These results indicated that haplotype effects containing local high-order epistasis effects had a tendency to be more important than global pairwise epistasis effects for the seven human phenotypes, and that the genetic mechanism of HDL and BMIo was more complex than that of the other traits.

Original languageEnglish (US)
Article number1478
Issue number10
StatePublished - Oct 2023

Bibliographical note

Publisher Copyright:
© 2023 by the authors.


  • SNP
  • epistasis
  • genomic prediction
  • haplotype
  • human phenotype
  • prediction accuracy

PubMed: MeSH publication types

  • Journal Article
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, N.I.H., Extramural


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