Brocard Simon, Morin Martin, Dos Santos Brito Silva Nayane, Renaud-Picard Benjamin, Coiffard Benjamin, Demant Xavier, Falque Loïc, Le Pavec Jérome, Roux Antoine, Villeneuve Thomas, Knoop Christiane, Mornex Jean-François, Salpin Mathilde, Boussaud Véronique, Rousseau Olivia, Mauduit Vincent, Durand Axelle, Magnan Antoine, Gourraud Pierre-Antoine, Vince Nicolas, Südholt Mario, Tissot Adrien, Limou Sophie
Nantes Université, CHU Nantes, Centrale Nantes, Inserm, Center for Research in Transplantation and Translational Immunology, UMR 1064, ITUN, Nantes, France.
IMT Atlantique - DAPI - Département Automatique, Productique et Informatique, Nantes, France.
Eur J Hum Genet. 2025 Mar;33(3):304-311. doi: 10.1038/s41431-024-01683-y. Epub 2024 Aug 20.
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.
长期肺移植（LT）存活的主要限制因素是慢性肺移植功能障碍（CLAD），它会导致不可逆的肺损伤和显著的死亡率。个体因素会影响CLAD，但迄今为止尚未进行大规模的基因研究。我们从COLT队列丰富且同质的子部分建立了多中心肺移植遗传队列（GenCOLT）生物样本库。GenCOLT收集了供体和受体的DNA、高质量的全基因组关联研究（GWAS）基因分型以及可靠的HLA数据，以补充COLT的临床数据。GenCOLT与全球COLT队列非常相似，在人口统计学、初始疾病和生存率等变量方面没有显著差异（P>0.05）。GenCOLT的供体平均年龄为45岁，女性占44%，主要死于中风（54%）。受体移植时平均年龄为48岁，女性占45%，主要基础疾病是慢性阻塞性肺疾病（45%）。平均随访时间为67个月，CLAD亚组5年生存率为57.3%，非CLAD亚组为97.4%。经过严格的质量控制后，GenCOLT为387对肺移植收集了超过730万个单核苷酸多态性（SNP）和HLA基因型，其中91%的配对由欧洲血统的供体和受体组成。总体而言，GenCOLT是2009年至2018年法国和比利时肺移植临床实践的准确缩影。它目前是致力于肺移植的最大基因生物样本库之一，同时拥有供体和受体的数据。这个独特的队列将有助于对CLAD和其他肺移植结果进行全面的GWAS研究。
