Using omics to explore complications of kidney transplantation

Stapleton, Caragh; Conlon, Peter J.; Phelan, Paul J.

doi:10.1111/tri.13067

Cited by 15 publications

(18 citation statements)

References 105 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…GWASs have been applied to numerous hematologic endpoints and have advanced our knowledge of the genetic underpinnings of modifiers of complete blood count, hematopoiesis, cardiovascular diseases, and sickle cell anemia . Transplant research has benefitted from GWASs by identifying novel genes and alleles that are associated with kidney transplant rejection and clinical outcomes in patients with renal and lung transplants . Although advances in whole genome sequencing have made it possible to interrogate causal variants directly as opposed to evaluating variants that are in linkage disequilibrium with causal variants, array‐based genotyping remains a cost‐effective method for genotyping large cohorts, such as the UK Biobank cohort, in which half a million participants have been enrolled and genotyped .…”

mentioning

confidence: 99%

Development and evaluation of a transfusion medicine genome wide genotyping array

et al. 2018

View full text Add to dashboard Cite

BACKGROUND: Many aspects of transfusion medicine are affected by genetics. Current single-nucleotide polymorphism (SNP) arrays are limited in the number of targets that can be interrogated and cannot detect all variation of interest. We designed a transfusion medicine array (TM-Array) for study of both common and rare transfusion-relevant variations in genetically diverse donor and recipient populations.STUDY DESIGN AND METHODS: The array was designed by conducting extensive bioinformatics mining and consulting experts to identify genes and genetic variation related to a wide range of transfusion medicine clinical relevant and research-related topics. Copy number polymorphisms were added in the alpha globin, beta globin, and Rh gene clusters. RESULTS:The final array contains approximately 879,000 SNP and copy number polymorphism markers. Over 99% of SNPs were called reliably. Technical replication showed the array to be robust and reproducible, with an error rate less than 0.03%. The array also had a very low Mendelian error rate (average parent-child trio accuracy of 0.9997). Blood group results were in concordance with serology testing results, and the array accurately identifies rare variants (minor allele frequency of 0.5%). The array achieved high genome-wide imputation coverage for African-American (97.5%), Hispanic (96.1%), East Asian (94.6%), and white (96.1%) genomes at a minor allele frequency of 5%. CONCLUSIONS: A custom array for transfusionmedicine research has been designed and evaluated. It gives wide coverage and accurate identification of rare SNPs in diverse populations. The TM-Array will be useful for future genetic studies in the diverse fields of transfusion medicine research. T ransfusion medicine encompasses diverse medical services and fields of research including blood donation, component processing, immunohematology, infectious disease, recipient outcomes, ABBREVIATIONS: BGMUT = blood group antigen gene mutation; CNPs = copy number polymorphisms; GWASs = genome-wide association studies; MAF = minor allele frequency; NHLBI = National Heart, Lung, and Blood Institute; RBC-Omics = Red Blood Cell Omics; REDS-III = Recipient Epidemiology Donor Evaluation Study-III; SCD = sickle cell disease; SNP = single-nucleotide polymorphism

show abstract

mentioning

confidence: 99%

Development and evaluation of a transfusion medicine genome wide genotyping array

et al. 2018

View full text Add to dashboard Cite

show abstract

“…There have been a few studies attempting to associate genetic variants with NODAT after kidney transplantation. [33][34][35] There have been reports that variants in the peroxisome proliferator-activated receptor α (PPARα) and P450 oxidoreductase (POR) genes are associated with increased risk for NODAT, but other studies do not validate these associations. 36,37 A recent case control study evaluating variants in kidney transplant recipients identified variants in the voltage-gated K+ channel (KCNQ1) gene, matrix metalloproteinase-2 (MMP2) gene and the glutathione peroxidans (GPX1) gene along with clinical factors have been reported to be associated with NODAT risk.…”

Section: Discussionmentioning

confidence: 99%

Genetic Variants Associated With Immunosuppressant Pharmacokinetics and Adverse Effects in the DeKAF Genomics Genome-wide Association Studies

Oetting

Schladt

et al. 2019

Transplantation

View full text Add to dashboard Cite

Background: The immunosuppressants tacrolimus and mycophenolate are important components to the success of organ transplantation, but are also associated with adverse effects such as nephrotoxicity, anemia, leukopenia and new onset diabetes after transplant (NODAT). In this report, we attempted to identify genetic variants which are associated with these adverse outcomes. Methods: We performed a genome-wide association study (GWAS), using a genotyping array tailored specifically for transplantation outcomes containing 722,147 SNPs, and two cohorts of kidney allograft recipients, a discovery cohort and a confirmation cohort, to identify and then confirm genetic variants associated with immunosuppressant pharmacokinetics and adverse outcomes. Results: Several genetic variants were found to be associated with tacrolimus trough concentrations. We did not confirm variants associated with the other phenotypes tested although several suggestive variants were identified. Discussion: These results show that adverse effects associated with tacrolimus and mycophenolate are complex and recipient risk is not determined by a few genetic variants with large effects with but most likely are due to many variants, each with small effect sizes, and clinical factors. Oetting et al.

show abstract

“…To date, only a handful of solid organ transplant GWA studies have been performed in modest numbers of patients and have focused mostly on renal transplantation (reviewed in an accompanying review article in this edition ) with very few significant findings. The only GWA study using heart transplant subjects was performed in relation to skin cancer outcomes .…”

Section: Genetics and Genome‐wide Studies In Heart Transplantationmentioning

confidence: 99%

Applying genomics in heart transplantation

et al. 2018

View full text Add to dashboard Cite

SUMMARY While advances in patient care and immunosuppressive pharmacotherapies have increased the lifespan of heart allograft recipients, there are still significant comorbidities post-transplantation and 5-year survival rates are still significant, at approximately 70%. The last decade has seen massive strides in genomics and other omics fields, including transcriptomics, with many of these advances now starting to impact heart transplant clinical care. This review summarizes a number of the key advances in genomics which are relevant for heart transplant outcomes, and we highlight the translational potential that such knowledge may bring to patient care within the next decade.

show abstract

Using omics to explore complications of kidney transplantation

Cited by 15 publications

References 105 publications

Development and evaluation of a transfusion medicine genome wide genotyping array

Development and evaluation of a transfusion medicine genome wide genotyping array

Genetic Variants Associated With Immunosuppressant Pharmacokinetics and Adverse Effects in the DeKAF Genomics Genome-wide Association Studies

Applying genomics in heart transplantation

Contact Info

Product

Resources

About