Description and first insights on a large genomic biobank of lung transplantation

Author:

Limou Sophie1ORCID,Brocard Simon1,Morin Martin,Silva Nayane Dos Santos Brito1,Renaud-Picard Benjamin2,Coiffard Benjamin3,Demant Xavier4,Falque Loïc5,Pavec Jérome Le6,Roux Antoine7,Villeneuve Thomas8,Knoop Christiane9,Mornex Jean-François10,Salpin Mathilde11,Boussaud Véronique12,Rousseau Olivia13ORCID,Mauduit VincentORCID,Durand AxelleORCID,Magnan Antoine14,Gourraud Pierre-Antoine15,Vince Nicolas16ORCID,Südholt Mario1,Tissot Adrien1

Affiliation:

1. Nantes University

2. Department of Respiratory Medicine and Strasbourg Lung Transplant Program

3. Aix Marseille Univ, Department of Respiratory Medicine and Lung Transplantation

4. Centre Hospitalier Universitaire de Bordeaux

5. Service Hospitalier Universitaire de Pneumologie et Physiologie, CHU Grenoble Alpes

6. Service de Pneumologie et Transplantation Pulmonaire, Groupe hospitalier Marie-Lannelongue -Saint Joseph, Le Plessis-Robinson

7. Pneumology, Adult Cystic Fibrosis Center and Lung Transplantation Department Hôpital Foch, Suresnes

8. CHU Toulouse, Service de Pneumologie

9. Service de Pneumologie, CHU Erasme, Bruxelles

10. Service de pneumologie, Orphalung, RESPIFIL Lyon

11. APHP Nord-Université Paris Cité, Hôpital Bichat, Service de Pneumologie B et Transplantation Pulmonaire, Paris

12. Service de Pneumologie, Hôpital Cochin, Paris

13. Nantes Université,

14. Hôpital Foch, Université de Versailles Saint Quentin Paris-Saclay

15. Université de Nantes

16. Nantes Université

Abstract

Abstract

The main limitation to long-term lung transplant (LT) survival is chronic lung allograft dysfunction (CLAD), which leads to irreversible lung damage and significant mortality. Individual factors can impact CLAD, but no large genetic investigation has been conducted to date. We established the multicentric Genetic COhort in Lung Transplantation (GenCOLT) biobank upon the rich and homogeneous COLT cohort. GenCOLT collected DNA, high-quality GWAS (genome-wide association study) genotyping and robust HLA data for donors and recipients to supplement COLT clinical data. GenCOLT closely mirrors the global COLT cohort without significant variations in variables like demographics, initial disease and survival rates (P > 0.05). The GenCOLT donors were 45 years-old on average, 44% women, and primarily died of stroke (54%). The recipients were 48 years-old at transplantation on average, 45% women, and the main underlying disease was chronic obstructive pulmonary disease (45%). The mean follow-up time was 67 months and survival at 5 years was 57.3% for the CLAD subgroup and 97.4% for the stable subgroup. After stringent quality controls, GenCOLT gathered more than 7.3 million SNP and HLA genotypes for 387 LT pairs, including 91% pairs composed of donor and recipient of European ancestry. Overall, GenCOLT is an accurate snapshot of LT clinical practice in France and Belgium between 2009 and 2018. It currently represents one of the largest genetic biobanks dedicated to LT with data available simultaneously for donors and recipients. This unique cohort will empower to run comprehensive GWAS investigations of CLAD and other LT outcomes.

Publisher

Springer Science and Business Media LLC

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