BibTex format
@article{Chin:2025:10.1101/2025.01.30.25321017,
author = {Chin, D and Hernandez-Beeftink, T and Donoghue, L and Guillen-Uio, B and Leavy, OC and Adegunsoye, A and Booth, HL and CleanUP-IPF, Investigators of the Pulmonary Trials Cooperative and Fahy, WA and Fingerlin, TE and Gooptu, B and Hall, IP and Hart, SP and Hill, MR and Hirani, N and Hubbard, RB and Johnson, S and Kaminski, N and Lorenzo-Salazar, JM and Ma, S-F and McAnulty, RJ and McCarthy, M and Stockwell, AD and Maher, TM and Millar, AB and Molyneaux, PL and Molina-Molina, M and Navaratnam, V and Neighbors, M and Oldham, JM and Parfrey, H and Saini, G and Sayers, I and Rebecca, Sheng X and Stewart, ID and Strek, ME and Tobin, MD and Whyte, MK and Zarcone, MC and Zhang, Y and Martinez, F and Yaspan, BL and Reynolds, CJ and Schwartz, DA and Flores, C and Noth, I and Gisli, Jenkins R and Allen, RJ and Wain, LV},
doi = {10.1101/2025.01.30.25321017},
journal = {medRxiv},
title = {Genome-wide association study of Idiopathic Pulmonary Fibrosis susceptibility using clinically-curated European-ancestry datasets.},
url = {http://dx.doi.org/10.1101/2025.01.30.25321017},
year = {2025}
}
RIS format (EndNote, RefMan)
TY - JOUR
AB - BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a rare, incurable lung disease with a median survival of 3-5 years after diagnosis. Treatment options are limited. Genetic association studies can identify new genes involved in disease that might represent potential new drug targets, and it has been shown that drug targets with support from genetic studies are more likely to be successful in clinical development. Previous genome-wide association studies (GWAS) of IPF susceptibility have identified more than 20 signals implicating genes involved in multiple mechanisms, including telomere dysfunction, cell-cell adhesion, host defence immunity, various signalling pathways and, more recently, mitotic spindle assembly complex. AIM: To leverage new datasets and genotype imputation to discover further genes involved in development of IPF that could yield new pathobiological avenues for exploration and to guide future drug target discovery. METHODS: We conducted a GWAS of IPF susceptibility including seven IPF case-control studies comprising 5,159 IPF cases and 27,459 controls of European ancestry, where IPF diagnosis was made by a respiratory clinician according to international guidelines. Genotypes were obtained from Whole Genome Sequencing (WGS) or from array-based imputation to the TOPMed WGS reference panel. New signals were replicated in independent biobanks with IPF defined using Electronic Healthcare Records. Bayesian fine-mapping was performed to identify the most likely causal variant(s) and bioinformatic investigation undertaken to map associated variants to putative causal genes. RESULTS: We identified three novel genetic signals of association with IPF susceptibility. Genes prioritised by functional evidence at these signals included MUC1, which encodes a large transmembrane glycoprotein and known biomarker of lung fibrosis, and NTN4 encoding Netrin-4 whose known roles include angiogenesis. The third signal may map to SLC6A6, a taurine and beta-alanine transp
AU - Chin,D
AU - Hernandez-Beeftink,T
AU - Donoghue,L
AU - Guillen-Uio,B
AU - Leavy,OC
AU - Adegunsoye,A
AU - Booth,HL
AU - CleanUP-IPF,Investigators of the Pulmonary Trials Cooperative
AU - Fahy,WA
AU - Fingerlin,TE
AU - Gooptu,B
AU - Hall,IP
AU - Hart,SP
AU - Hill,MR
AU - Hirani,N
AU - Hubbard,RB
AU - Johnson,S
AU - Kaminski,N
AU - Lorenzo-Salazar,JM
AU - Ma,S-F
AU - McAnulty,RJ
AU - McCarthy,M
AU - Stockwell,AD
AU - Maher,TM
AU - Millar,AB
AU - Molyneaux,PL
AU - Molina-Molina,M
AU - Navaratnam,V
AU - Neighbors,M
AU - Oldham,JM
AU - Parfrey,H
AU - Saini,G
AU - Sayers,I
AU - Rebecca,Sheng X
AU - Stewart,ID
AU - Strek,ME
AU - Tobin,MD
AU - Whyte,MK
AU - Zarcone,MC
AU - Zhang,Y
AU - Martinez,F
AU - Yaspan,BL
AU - Reynolds,CJ
AU - Schwartz,DA
AU - Flores,C
AU - Noth,I
AU - Gisli,Jenkins R
AU - Allen,RJ
AU - Wain,LV
DO - 10.1101/2025.01.30.25321017
PY - 2025///
TI - Genome-wide association study of Idiopathic Pulmonary Fibrosis susceptibility using clinically-curated European-ancestry datasets.
T2 - medRxiv
UR - http://dx.doi.org/10.1101/2025.01.30.25321017
UR - https://www.ncbi.nlm.nih.gov/pubmed/39974050
ER -