Description and first insights on a large genomic biobank of lung transplantation
Simon Brocard
(1, 2)
,
Martin Morin
(1, 2)
,
Nayane dos Santos Brito Silva
(1, 2, 3)
,
Benjamin Renaud-Picard
(4, 5)
,
Benjamin Coiffard
(6, 7, 8)
,
Xavier Demant
(9)
,
Loïc Falque
(10)
,
Jérome Le Pavec
(11, 12)
,
Antoine Roux
(13)
,
Thomas Villeneuve
(14)
,
Christiane Knoop
(15)
,
Jean-François Mornex
(16)
,
Mathilde Salpin
(17)
,
Véronique Boussaud
(18)
,
Olivia Rousseau
(1, 2)
,
Vincent Mauduit
(2, 1)
,
Axelle Durand
(1, 2)
,
Antoine Magnan
(13)
,
Pierre-Antoine Gourraud
(1, 2)
,
Nicolas Vince
(1, 2)
,
Mario Südholt
(19, 20)
,
Adrien Tissot
(1, 21)
,
Sophie Limou
(1, 22, 2)
1
U1064 Inserm - CR2TI -
Centre de Recherche en Transplantation et Immunologie - Center for Research in Transplantation and Translational Immunology
2 Team 3 - U1064 Inserm - CR2TI - Team 3 : Integrative transplantation, HLA, Immunology and genomics of kidney injury
3 UNESP - Universidade Estadual Paulista Júlio de Mesquita Filho = São Paulo State University
4 HUS - Les Hôpitaux Universitaires de Strasbourg
5 NanoRegMed - Nanomédecine Régénérative
6 MEPHI - Microbes évolution phylogénie et infections
7 IHU Marseille - Institut Hospitalier Universitaire Méditerranée Infection
8 Hôpital Nord [CHU - APHM]
9 CHU Bordeaux - Centre Hospitalier Universitaire de Bordeaux
10 Pôle Thorax et Vaisseaux [CHU Grenoble]
11 HPPIT - Hypertension pulmonaire : physiopathologie et innovation thérapeutique
12 Hôpital Marie-Lannelongue
13 Hôpital Foch [Suresnes]
14 Pôle Clinique des Voies respiratoires [CHU Toulouse]
15 HUB-ULB - Hôpital Erasme = Erasmus Hospital = Erasmus Ziekenhuis
16 IVPC - Infections Virales et Pathologie Comparée - UMR 754
17 AP-HP - Hôpital Bichat - Claude Bernard [Paris]
18 HEGP - Hôpital Européen Georges Pompidou [APHP]
19 IMT Atlantique - DAPI - Département Automatique, Productique et Informatique
20 STACK - Software Stack for Massively Geo-Distributed Infrastructures
21 Team 4 - U1064 Inserm - CR2TI - Team 4 : Deciphering organ immune regulation in inflammation and transplantation (DORI-t)
22 Nantes Univ - ECN - NANTES UNIVERSITÉ - École Centrale de Nantes
2 Team 3 - U1064 Inserm - CR2TI - Team 3 : Integrative transplantation, HLA, Immunology and genomics of kidney injury
3 UNESP - Universidade Estadual Paulista Júlio de Mesquita Filho = São Paulo State University
4 HUS - Les Hôpitaux Universitaires de Strasbourg
5 NanoRegMed - Nanomédecine Régénérative
6 MEPHI - Microbes évolution phylogénie et infections
7 IHU Marseille - Institut Hospitalier Universitaire Méditerranée Infection
8 Hôpital Nord [CHU - APHM]
9 CHU Bordeaux - Centre Hospitalier Universitaire de Bordeaux
10 Pôle Thorax et Vaisseaux [CHU Grenoble]
11 HPPIT - Hypertension pulmonaire : physiopathologie et innovation thérapeutique
12 Hôpital Marie-Lannelongue
13 Hôpital Foch [Suresnes]
14 Pôle Clinique des Voies respiratoires [CHU Toulouse]
15 HUB-ULB - Hôpital Erasme = Erasmus Hospital = Erasmus Ziekenhuis
16 IVPC - Infections Virales et Pathologie Comparée - UMR 754
17 AP-HP - Hôpital Bichat - Claude Bernard [Paris]
18 HEGP - Hôpital Européen Georges Pompidou [APHP]
19 IMT Atlantique - DAPI - Département Automatique, Productique et Informatique
20 STACK - Software Stack for Massively Geo-Distributed Infrastructures
21 Team 4 - U1064 Inserm - CR2TI - Team 4 : Deciphering organ immune regulation in inflammation and transplantation (DORI-t)
22 Nantes Univ - ECN - NANTES UNIVERSITÉ - École Centrale de Nantes
Nayane dos Santos Brito Silva
- Fonction : Auteur
Xavier Demant
- Fonction : Auteur
- PersonId : 1304764
- ORCID : 0000-0003-0045-2018
Pierre-Antoine Gourraud
- Fonction : Auteur
- PersonId : 762977
- ORCID : 0000-0003-1131-9554
- IdRef : 195137280
Nicolas Vince
- Fonction : Auteur
- PersonId : 1131457
- IdHAL : nicolas-vince
- ORCID : 0000-0002-3767-6210
- IdRef : 147938937
Mario Südholt
- Fonction : Auteur
- PersonId : 8562
- IdHAL : mario-sudholt
- ORCID : 0000-0002-1855-1519
- IdRef : 156513013
Adrien Tissot
- Fonction : Auteur
- PersonId : 1355190
- ORCID : 0000-0002-3259-6430
- IdRef : 170047148
Sophie Limou
- Fonction : Auteur
- PersonId : 1191789
- ORCID : 0000-0002-7702-8234
- IdRef : 146362705
Résumé
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 from a rich and homogeneous sub-part of 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 non-CLAD 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.
