@misc{10481/74741,
year = {2022},
month = {1},
url = {http://hdl.handle.net/10481/74741},
abstract = {Introduction 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.
Methods 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.
Results 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.
Conclusions This study suggests the existence of a common genetic aetiology between LAM and
pulmonary function.},
organization = {Asociacion Espanola de LAM},
organization = {LAM Foundation Seed Grant 2019},
organization = {Instituto de Salud Carlos III	PI18/01029	
PI21/01306	
ICI19/00047},
organization = {European Regional Development Fund (ERDF), "A way to build Europe"},
organization = {Ministry of Economy and Competitivity	SAF2017-88457-R},
organization = {Generalitat de Catalunya},
organization = {General Electric	SGR 2017-449	
2017-529},
organization = {PERIS PFI-Salut	SLT017-20-000076},
organization = {CERCA Program},
organization = {VEIS project	001-P-001647},
organization = {ERDF, "A way to build Europe"		
ERDF Operational Programme of Catalonia 2014-2020},
publisher = {European Respiratory Society},
title = {Evidence for shared genetic risk factors between lymphangioleiomyomatosis and pulmonary function},
doi = {10.1183/23120541.00375-2021},
author = {Farré, Xavier and Tena Garitaonaindia, Mireia and Sánchez De Medina López-Huertas, Fermín},
}