关于肺移植大型基因组生物库的描述和初步见解。

IF 3.7 2区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Simon Brocard, Martin Morin, Nayane Dos Santos Brito Silva, Benjamin Renaud-Picard, Benjamin Coiffard, Xavier Demant, Loïc Falque, Jérome Le Pavec, Antoine Roux, Thomas Villeneuve, Christiane Knoop, Jean-François Mornex, Mathilde Salpin, Véronique Boussaud, Olivia Rousseau, Vincent Mauduit, Axelle Durand, Antoine Magnan, Pierre-Antoine Gourraud, Nicolas Vince, Mario Südholt, Adrien Tissot, Sophie Limou
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引用次数: 0

摘要

肺移植(LT)长期存活的主要限制因素是慢性肺异体移植功能障碍(CLAD),它会导致不可逆的肺损伤和严重的死亡率。个体因素会对 CLAD 产生影响,但迄今为止尚未开展过大规模的遗传调查。我们从 COLT 队列的一个丰富且同质的子部分建立了多中心肺移植基因队列(GenCOLT)生物库。GenCOLT 收集了供体和受体的 DNA、高质量 GWAS(全基因组关联研究)基因分型和强大的 HLA 数据,作为 COLT 临床数据的补充。GenCOLT 与全球 COLT 队列密切相关,在人口统计学、初始疾病和存活率等变量方面没有显著差异(P > 0.05)。GenCOLT 捐赠者平均年龄 45 岁,44% 为女性,主要死于中风(54%)。受者移植时平均年龄为 48 岁,45% 为女性,主要基础疾病为慢性阻塞性肺病(45%)。平均随访时间为 67 个月,CLAD 亚组的 5 年存活率为 57.3%,非 CLAD 亚组的 5 年存活率为 97.4%。经过严格的质量控制,GenCOLT为387对LT患者收集了730多万个SNP和HLA基因型,其中91%的患者为欧洲血统的供体和受体。总体而言,GenCOLT 是 2009 年至 2018 年期间法国和比利时 LT 临床实践的准确缩影。它是目前最大的LT基因生物库之一,可同时提供供体和受体的数据。这一独特的队列将有助于对CLAD和其他LT结果进行全面的GWAS调查。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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

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

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.

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来源期刊
European Journal of Human Genetics
European Journal of Human Genetics 生物-生化与分子生物学
CiteScore
9.90
自引率
5.80%
发文量
216
审稿时长
2 months
期刊介绍: The European Journal of Human Genetics is the official journal of the European Society of Human Genetics, publishing high-quality, original research papers, short reports and reviews in the rapidly expanding field of human genetics and genomics. It covers molecular, clinical and cytogenetics, interfacing between advanced biomedical research and the clinician, and bridging the great diversity of facilities, resources and viewpoints in the genetics community. Key areas include: -Monogenic and multifactorial disorders -Development and malformation -Hereditary cancer -Medical Genomics -Gene mapping and functional studies -Genotype-phenotype correlations -Genetic variation and genome diversity -Statistical and computational genetics -Bioinformatics -Advances in diagnostics -Therapy and prevention -Animal models -Genetic services -Community genetics
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