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Identify New Genetic Variants on Chromosome 6 Associated with Mortality after Heart Transplantation

Zar, G. LU ; Vihinen, M. LU orcid and Nilsson, J. LU orcid (2020) In The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation 39(4). p.473-473
Abstract

PURPOSE: Graft failure in heart transplant recipients is still the leading cumulative cause of death, rejection related injuries likely being an important contributor. In this study we used a genome-wide association approach using whole-genome data from chromosome 6 to analyze genetic associations with survival after heart transplantation. METHODS: The study included recipient samples from patients who had undergone heart transplantation at Skane University Hospital, Lund, Sweden, between 1988 and 2009. Patients with at least one grade 3 rejection episode and/or survival <10 years were included, as well as individuals in control group with no grade 3 rejection episodes or survival >10 years. Endomyocardial biopsies were sent to... (More)

PURPOSE: Graft failure in heart transplant recipients is still the leading cumulative cause of death, rejection related injuries likely being an important contributor. In this study we used a genome-wide association approach using whole-genome data from chromosome 6 to analyze genetic associations with survival after heart transplantation. METHODS: The study included recipient samples from patients who had undergone heart transplantation at Skane University Hospital, Lund, Sweden, between 1988 and 2009. Patients with at least one grade 3 rejection episode and/or survival <10 years were included, as well as individuals in control group with no grade 3 rejection episodes or survival >10 years. Endomyocardial biopsies were sent to the Broad Institute for DNA extraction and whole-genome sequencing. Variant calling and variant recalibration and filtering was conducted with the Genome Analysis Toolkit (GATK). A genome-wide association analysis using PLINK utilizing allelic association using chi-square test was performed. RESULTS: Genome-wide association analysis was conducted on a total of 34 patients using 470502 single nucleotide variants on chromosome 6. Thirteen associations yielded p > 1 × 10-5. We found 3 variants associated with mortality and after heart transplantation, rs66723041 (1.88 × 10-6), rs68123256 (6.28 × 10-6) and rs66758173 (6.28 × 10-6) in the gene HLA-DRB6. CONCLUSION: This first of its kind genome-wide association analysis demonstrates genetic variants associated with mortality and survival after heart transplantation. No association attained genome-wide significance, but several intriguing findings emerged. Notably, a cluster of low p-value SNVs were observed at HLA-DRB6 associated with mortality after heart transplantation. Genetic approaches such as these may lead to the identification of novel biological pathways and the development of new pharmaceutical targets and biomarkers.

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author
; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation
volume
39
issue
4
pages
473 - 473
publisher
Elsevier
external identifiers
  • scopus:85085636250
  • pmid:32465841
ISSN
1557-3117
DOI
10.1016/j.healun.2020.01.015
language
English
LU publication?
yes
id
395d225c-8f12-4217-96c7-5998fa82a955
date added to LUP
2020-06-24 12:51:15
date last changed
2021-05-11 01:28:32
@misc{395d225c-8f12-4217-96c7-5998fa82a955,
  abstract     = {{<p>PURPOSE: Graft failure in heart transplant recipients is still the leading cumulative cause of death, rejection related injuries likely being an important contributor. In this study we used a genome-wide association approach using whole-genome data from chromosome 6 to analyze genetic associations with survival after heart transplantation. METHODS: The study included recipient samples from patients who had undergone heart transplantation at Skane University Hospital, Lund, Sweden, between 1988 and 2009. Patients with at least one grade 3 rejection episode and/or survival &lt;10 years were included, as well as individuals in control group with no grade 3 rejection episodes or survival &gt;10 years. Endomyocardial biopsies were sent to the Broad Institute for DNA extraction and whole-genome sequencing. Variant calling and variant recalibration and filtering was conducted with the Genome Analysis Toolkit (GATK). A genome-wide association analysis using PLINK utilizing allelic association using chi-square test was performed. RESULTS: Genome-wide association analysis was conducted on a total of 34 patients using 470502 single nucleotide variants on chromosome 6. Thirteen associations yielded p &gt; 1 × 10-5. We found 3 variants associated with mortality and after heart transplantation, rs66723041 (1.88 × 10-6), rs68123256 (6.28 × 10-6) and rs66758173 (6.28 × 10-6) in the gene HLA-DRB6. CONCLUSION: This first of its kind genome-wide association analysis demonstrates genetic variants associated with mortality and survival after heart transplantation. No association attained genome-wide significance, but several intriguing findings emerged. Notably, a cluster of low p-value SNVs were observed at HLA-DRB6 associated with mortality after heart transplantation. Genetic approaches such as these may lead to the identification of novel biological pathways and the development of new pharmaceutical targets and biomarkers.</p>}},
  author       = {{Zar, G. and Vihinen, M. and Nilsson, J.}},
  issn         = {{1557-3117}},
  language     = {{eng}},
  note         = {{Conference Abstract}},
  number       = {{4}},
  pages        = {{473--473}},
  publisher    = {{Elsevier}},
  series       = {{The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation}},
  title        = {{Identify New Genetic Variants on Chromosome 6 Associated with Mortality after Heart Transplantation}},
  url          = {{http://dx.doi.org/10.1016/j.healun.2020.01.015}},
  doi          = {{10.1016/j.healun.2020.01.015}},
  volume       = {{39}},
  year         = {{2020}},
}