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KiT-GENIE, the French genetic biobank of kidney transplantation

European Journal of Human Genetics (2023)Cite this article

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Abstract

KiT-GENIE is a monocentric DNA biobank set up to consolidate the very rich and homogeneous DIVAT French cohort of kidney donors and recipients (D/R) in order to explore the molecular factors involved in kidney transplantation outcomes. We collected DNA samples for kidney transplantations performed in Nantes, and we leveraged GWAS genotyping data for securing high-quality genetic data with deep SNP and HLA annotations through imputations and for inferring D/R genetic ancestry. Overall, the biobank included 4217 individuals (n = 1945 D + 2,272 R, including 1969 D/R pairs), 7.4 M SNPs and over 200 clinical variables. KiT-GENIE represents an accurate snapshot of kidney transplantation clinical practice in Nantes between 2002 and 2018, with an enrichment in living kidney donors (17%) and recipients with focal segmental glomerulosclerosis (4%). Recipients were predominantly male (63%), of European ancestry (93%), with a mean age of 51yo and 86% experienced their first graft over the study period. D/R pairs were 93% from European ancestry, and 95% pairs exhibited at least one HLA allelic mismatch. The mean follow-up time was 6.7 years with a hindsight up to 25 years. Recipients experienced biopsy-proven rejection and graft loss for 16.6% and 21.3%, respectively. KiT-GENIE constitutes one of the largest kidney transplantation genetic cohorts worldwide to date. It includes homogeneous high-quality clinical and genetic data for donors and recipients, hence offering a unique opportunity to investigate immunogenetic and genetic factors, as well as donor-recipient interactions and mismatches involved in rejection, graft survival, primary disease recurrence and other comorbidities.

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Fig. 1: Building the KiT-GENIE DNA biocollection and GWAS SNP data.
Fig. 2: Distribution of KiT-GENIE recipients according to the year of graft.
Fig. 3: PCA projection of KiT-GENIE individuals with the 1000 Genomes Project reference individuals.
Fig. 4: Genetic ancestry matching between donors and recipients.

Data availability

The KiT-GENIE data are available from our CR2TI team. Data and summary statistics are available upon reasonable request following approval from the KiT-GENIE steering committee and ethics committee to ensure data protection and privacy in compliance with French and European laws. Collaborations are encouraged through specific research projects using the KiT-GENIE data or through enriching the existing cohort with new patients. Potential collaborators are invited to contact the primary investigator Sophie Limou: sophie.limou@univ-nantes.fr.

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Acknowledgements

We thank everyone who helped in the design, collection, genotyping experiments, data cleaning and analyses. We are especially indebted to all donors and recipients who participated in this study, to the clinical staff and physicians who care and manage the patients on a daily basis and helped recruiting the patients, and to research associates who participated in the data collection. Clinical data were collected from the French DIVAT multicentric prospective cohort of kidney and/or pancreatic transplant recipients by focusing on the Nantes centre (www.divat.fr, n° CNIL 914184, ClinicalTrials.gov identifier: NCT02900040). The analysis and interpretation of these data are the responsibility of the authors. We would like to acknowledge the local blood bank and HLA typing lab (Etablissement Français du Sang [EFS] Nantes) for facilitating the access to DNA samples. Finally, we thank the GenoBiRD and Curie genomic platforms for technical support and GWAS genotyping.

Funding

The KiT-GENIE cohort has been funded by several entities: (1) The Etoiles Montantes funding by the Pays de la Loire region (n°2018-09998), (2) The IRCT Dialyse research project by the Société Francophone de Néphrologie, Dialyse et Transplantation (SFNDT), (3) The Greffe research project by French Agence de la Biomédecine (ABM, n°18GREFFE014). In addition, this work has benefited from government support through the National Research Agency (ANR) under the future investment program (n°ANR-17-RHUS-0010) and from the European Union’s Horizon 2020 Research and Innovation Programme (n°754995). Finally, we thank the Roche Pharma, Novartis, Astellas, Chiesi, Sandoz and Sanofi laboratories for supporting the DIVAT cohort as the CENTAURE Foundation (http://www.fondation-centaure.org).

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Authors and Affiliations

  1. Nantes Université, Centrale Nantes, CHU Nantes, Inserm, Centre de Recherche Translationnelle en Transplantation et Immunologie, UMR 1064, F-44000, Nantes, France

    Rokhaya Ba, Axelle Durand, Vincent Mauduit, Christine Chauveau, Stéphanie Le Bas-Bernardet, Sonia Salle, Martin Morin, Clémence Petit, Venceslas Douillard, Olivia Rousseau, Gilles Blancho, Nicolas Vince, Magali Giral, Pierre-Antoine Gourraud & Sophie Limou

  2. CHU Nantes, Nantes Université, Service de Néphrologie-Immunologie Clinique, ITUN, F-44000, Nantes, France

    Pierrick Guérif, Clémence Petit, Gilles Blancho, Clarisse Kerleau & Magali Giral

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Contributions

RB, AD and SL were involved in the design, conception, implementation and data collection of KiT-GENIE. RB, AD, CC, SLBB, SS, PG, and CP were involved in DNA collection and normalisation. RB, AD, VM, MM, VD, OR and SL were involved in quality controls, statistical description, imputation of missing data, PCA analysis and ancestry analysis. CK realized clinical data extraction from the DIVAT database. MG and GB provided clinical guidance and ensured access to the DIVAT clinical data. RB and SL wrote the article. SL, PAG and NV supervised the building of KiT-GENIE, revised and formalized the scientific content of the article and mentored RB. All authors have read and approved the final version of the manuscript.

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Correspondence to Sophie Limou.

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The authors declare no competing interests.

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Written consent was obtained from each participant for access to clinical data and participation to DNA analyses (DIVAT n° CNIL 914184). Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

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Ba, R., Durand, A., Mauduit, V. et al. KiT-GENIE, the French genetic biobank of kidney transplantation. Eur J Hum Genet (2023). https://doi.org/10.1038/s41431-023-01294-z

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