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GenCOLT: a multicenter European biobank for investigating genome-wide determinants of lung transplant outcomes

European Journal of Human Genetics volume 33, pages 261–262 (2025)Cite this article

The Original Article was published on 20 August 2024

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.

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References

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Funding

Funding for BJK was provided through support from NIAID U01 AI152960.

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Authors and Affiliations

  1. Division of Transplantation, Department of Surgery, New York University Langone Health, New York, NY, USA

    Brendan J. Keating

  2. Institute of Systems Genetics, New York University Langone Health, New York, NY, USA

    Brendan J. Keating

  3. Division of Transplantation, Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Brendan J. Keating

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  1. Brendan J. Keating
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BJK conceptualized and wrote the manuscript.

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Correspondence to Brendan J. Keating.

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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

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