Gencolt: a multicenter european biobank for investigating genome-wide determinants of lung transplant outcomes

Gencolt: a multicenter european biobank for investigating genome-wide determinants of lung transplant outcomes


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Access through your institution Buy or subscribe The International Society for Heart and Lung Transplantation (LTx) estimates that over 4600 lung transplants are currently performed


worldwide each year. These LTx procedures represent less than 3% of all solid-organ transplants and the 5-year survival of recipients is generally poorer with 5 years post-transplantation


survival rates of ~63% in Europe and ~54% in the United States. Development of chronic lung allograft dysfunction (CLAD), which causes irreversible lung damage, is the main contributor to


long-term lung LTx survival. Phenotypically CLAD can exhibit clinical heterogeneity of with two phenotypes being described: bronchiolitis obliterans syndrome (BOS) and restrictive allograft


syndrome (RAS). BOS is generally characterized by the presence of obstructive pulmonary function, air trapping evident on CT scans, with histopathological evidence of obliterative


bronchiolitis (OB). RAS patients present with restrictive pulmonary function, with persistent pleuro-parenchymal infiltrates evident on CT scans, and a type of scarring in the upper lobes of


the lungs, termed pleuroparenchymal fibro-elastosis, evident on lung biopsies. While various risk factors have been identified, there is a paucity of genome-wide association studies


performed to date for CLAD [1]. In this issue of _EJHG_, Brocard et al. describe the multicentric Genetic COhort in Lung Transplantation (GenCOLT) study, a powerful biobank resource to


investigate the genetic determinants of long-term outcomes in lung transplantation [2]. GenCOLT has collected DNA and generated high-quality genome-wide genotyping and HLA Class I/II


datasets for 387 LTx donor and recipient pairs from the overarching COLT study which comprised over 1400 lung transplant procedures across 12 French and Belgian LTx centers. GenCOLT donors


were on average 45 years old, with 44% women, with the primary cause of death being stroke (54%). The average age of GenCOLT recipients at the time of LTx was 48 years old, 45% are women,


with chronic obstructive pulmonary disease being the primary disease etiology (45%) precipitating the need for LTx. The average follow-up time in GenCOLT is 67 months between 2009 and 2018,


with a 5-year survival average of 57.3% observed for the CLAD subgroup and 97.4% observed for the non-CLAD subgroup. The GenCOLT cohort was generally equivalent for clinical covariates,


demographics, primary disease etiology and survival rates with the larger COLT study. Genetic variations can impact a wide range of processes, including immune responses, inflammation, and


tissue repair, all of which play crucial roles in the development of CLAD and other complications [1]. By understanding the genetic basis of these processes, researchers can develop more


accurate risk prediction models, identify novel therapeutic targets, and ultimately improve the long-term success of lung transplantation. This unique European resource combines extensive


clinical data with high-quality genome-wide genetic information from both donors and recipients, for genome-wide association studies (GWAS) to be performed in CLAD and more widely in


additional phenotypes and outcomes impacting lung transplantation. This is a preview of subscription content, access via your institution ACCESS OPTIONS Access through your institution


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Contact customer support REFERENCES * Napoli C, Benincasa G, Fiorelli A, Strozziero MG, Costa D, Russo F, et al. Lung transplantation: current insights and outcomes. Transpl Immunol.


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cohort. Lancet. 2019;393:910–7. Article  PubMed  Google Scholar  Download references FUNDING Funding for BJK was provided through support from NIAID U01 AI152960. AUTHOR INFORMATION AUTHORS


AND AFFILIATIONS * Division of Transplantation, Department of Surgery, New York University Langone Health, New York, NY, USA Brendan J. Keating * Institute of Systems Genetics, New York


University Langone Health, New York, NY, USA Brendan J. Keating * Division of Transplantation, Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia,


PA, USA Brendan J. Keating Authors * Brendan J. Keating View author publications You can also search for this author inPubMed Google Scholar CONTRIBUTIONS BJK conceptualized and wrote the


manuscript. CORRESPONDING AUTHOR Correspondence to Brendan J. Keating. ETHICS DECLARATIONS COMPETING INTERESTS The author declares no competing interests. ADDITIONAL INFORMATION PUBLISHER’S


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CITE THIS ARTICLE Keating, B.J. GenCOLT: a multicenter European biobank for investigating genome-wide determinants of lung transplant outcomes. _Eur J Hum Genet_ 33, 261–262 (2025).


https://doi.org/10.1038/s41431-024-01712-w Download citation * Received: 01 October 2024 * Accepted: 01 October 2024 * Published: 06 November 2024 * Issue Date: March 2025 * DOI:


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