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Joint testing of donor and recipient genetic matching scores and recipient genotype has robust power for finding genes associated with transplant outcomes.

Authors
  • Arthur, Victoria L1
  • Guan, Weihua2
  • Loza, Bao-Li3
  • Keating, Brendan3
  • Chen, Jinbo1
  • 1 Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
  • 2 Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, Minnesota.
  • 3 Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania.
Type
Published Article
Journal
Genetic Epidemiology
Publisher
Wiley (John Wiley & Sons)
Publication Date
Nov 01, 2020
Volume
44
Issue
8
Pages
893–907
Identifiers
DOI: 10.1002/gepi.22349
PMID: 32783273
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Genetic matching between transplant donor and recipient pairs has traditionally focused on the human leukocyte antigen (HLA) regions of the genome, but recent studies suggest that matching for non-HLA regions may be important as well. We assess four genetic matching scores for use in association analyses of transplant outcomes. These scores describe genetic ancestry distance using identity-by-state, or genetic incompatibility or mismatch of the two genomes and therefore may reflect different underlying biological mechanisms for donor and recipient genes to influence transplant outcomes. Our simulation studies show that jointly testing these scores with the recipient genotype is a powerful method for preliminary screening and discovery of transplant outcome related single nucleotide polymorphisms (SNPs) and gene regions. Following these joint tests with marginal testing of the recipient genotype and matching score separately can lead to further understanding of the biological mechanisms behind transplant outcomes. In addition, we present results of a liver transplant data analysis that shows joint testing can detect SNPs significantly associated with acute rejection in liver transplant. © 2020 Wiley Periodicals LLC.

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