Recessive/dominant model: Alternative choice in case-control-based genome-wide association studies

PLoS One. 2021 Jul 21;16(7):e0254947. doi: 10.1371/journal.pone.0254947. eCollection 2021.

Abstract

An additive genetic model is usually employed in case-control-based genome-wide association studies. The model usually encodes "AA", "Aa" and "aa" ("a" represents the minor allele) as three different numbers, implying the contribution of genotype "Aa" to the phenotype is different from "AA" and "aa". From the perspective of biological phenomena, the coding is reasonable since the phenotypes of lives are not "black and white". A case-control based study, however, has only two phenotypes, case and control, which means that the phenotypes are "black and white". It suggests that a recessive/dominant model may be an alternative to the additive model. In order to investigate whether the alternative is feasible, we conducted comparative experiments on several models used in those studies through chi-square test and logistic regression. Our simulation experiments demonstrate that a recessive model is better than the additive model. The area under the curve of the former has increased by 5% compared with the latter, the discrimination of identifying risk single nucleotide polymorphisms has been improved by 61%, and the precision has also reached 1.10 times that of the latter. Furthermore, the real data experiments show that the precision and area under the curve of the former are 16% and 20% higher than the latter respectively, and the area under the curve of dominant model of the former is 13% higher than the latter. The results indicate a recessive/dominant model may be an alternative to the additive model and suggest a new route for case-control-based studies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Case-Control Studies
  • Coronary Artery Disease / genetics*
  • Databases, Nucleic Acid*
  • Genes, Dominant*
  • Genes, Recessive*
  • Genome-Wide Association Study
  • Humans
  • Models, Genetic*
  • Polymorphism, Single Nucleotide*

Grants and funding

This study was supported by the National Natural Science Foundation of China (http://www.nsfc.gov.cn/) under grant number 31660321 which was awarded to H.M LIU. No author received salary or other funding from commercial companies. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.