RT Journal Article
T1 Evidence for shared genetic risk factors between lymphangioleiomyomatosis and pulmonary function.
A1 Farre, Xavier
A1 Espin, Roderic
A1 Baiges, Alexandra
A1 Blommaert, Eline
A1 Kim, Wonji
A1 Giannikou, Krinio
A1 Herranz, Carmen
A1 Roman, Antonio
A1 Saez, Berta
A1 Casanova, Alvaro
A1 Ancochea, Julio
A1 Valenzuela, Claudia
A1 Ussetti, Piedad
A1 Laporta, Rosalia
A1 Rodriguez-Portal, Jose A
A1 van Moorsel, Coline H M
A1 van der Vis, Joanne J
A1 Quanjel, Marian J R
A1 Tena-Garitaonaindia, Mireia
A1 Sanchez de Medina, Fermín
A1 Mateo, Francesca
A1 Molina-Molina, Maria
A1 Won, Sungho
A1 Kwiatkowski, David J
A1 de Cid, Rafael
A1 Pujana, Miquel Angel
K1 Humans
K1 Female
K1 Forced Expiratory Volume
K1 Genome-Wide Association Study
K1 Transcriptome
AB Lymphangioleiomyomatosis (LAM) is a rare low-grade metastasising disease characterised by cystic lung destruction. The genetic basis of LAM remains incompletely determined, and the disease cell-of-origin is uncertain. We analysed the possibility of a shared genetic basis between LAM and cancer, and LAM and pulmonary function. The results of genome-wide association studies of LAM, 17 cancer types and spirometry measures (forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC ratio and peak expiratory flow (PEF)) were analysed for genetic correlations, shared genetic variants and causality. Genomic and transcriptomic data were examined, and immunodetection assays were performed to evaluate pleiotropic genes. There were no significant overall genetic correlations between LAM and cancer, but LAM correlated negatively with FVC and PEF, and a trend in the same direction was observed for FEV1. 22 shared genetic variants were uncovered between LAM and pulmonary function, while seven shared variants were identified between LAM and cancer. The LAM-pulmonary function shared genetics identified four pleiotropic genes previously recognised in LAM single-cell transcriptomes: ADAM12, BNC2, NR2F2 and SP5. We had previously associated NR2F2 variants with LAM, and we identified its functional partner NR3C1 as another pleotropic factor. NR3C1 expression was confirmed in LAM lung lesions. Another candidate pleiotropic factor, CNTN2, was found more abundant in plasma of LAM patients than that of healthy women. This study suggests the existence of a common genetic aetiology between LAM and pulmonary function.
PB European Respiratory Society
SN 2312-0541
YR 2021
FD 2021-09-17
LK http://hdl.handle.net/10668/20258
UL http://hdl.handle.net/10668/20258
LA en
NO Farré X, Espín R, Baiges A, Blommaert E, Kim W, Giannikou K,  et al. Evidence for shared genetic risk factors between lymphangioleiomyomatosis and pulmonary function. ERJ Open Res. 2022 Jan 24;8(1):00375-2021.
NO This research was supported by Asociación Española de LAM; The LAM Foundation Seed Grant2019; Carlos III Institute of Health grants PI18/01029, PI21/01306 and ICI19/00047 (co-funded by European RegionalDevelopment Fund (ERDF), “A way to build Europe”); Ministry of Economy and Competitivity grantSAF2017-88457-R; the Generalitat de Catalunya SGR 2017-449 and 2017-529; PERIS PFI-Salut SLT017-20-000076; andthe CERCA Program to IDIBELL and Institut Germans Trias i Pujol. X. Farré is supported by the VEIS project(001-P-001647, ERDF Operational Programme of Catalonia 2014–2020; co-funded by ERDF, “A way to buildEurope”). Funding information for this article has been deposited with the Crossref Funder Registry
DS RISalud
RD May 9, 2025