BibTex format

author = {Oldham, JM and Allen, RJ and Lorenzo-Salazar, JM and Molyneaux, PL and Ma, S-F and Joseph, C and Kim, JS and Guillen-Guio, B and Hernández-Beeftink, T and Kropski, JA and Huang, Y and Lee, CT and Adegunsoye, A and Pugashetti, JV and Linderholm, AL and Vo, V and Strek, ME and Jou, J and Muñoz-Barrera, A and Rubio-Rodriguez, LA and Hubbard, R and Hirani, N and Whyte, MKB and Hart, S and Nicholson, AG and Lancaster, L and Parfrey, H and Rassl, D and Wallace, W and Valenzi, E and Zhang, Y and Mychaleckyj, J and Stockwell, A and Kaminski, N and Wolters, PJ and Molina-Molina, M and Banovich, NE and Fahy, WA and Martinez, FJ and Hall, IP and Tobin, MD and Maher, TM and Blackwell, TS and Yaspan, BL and Jenkins, RG and Flores, C and Wain, LV and Noth, I},
doi = {10.1164/rccm.202205-0845OC},
journal = {American Journal of Respiratory and Critical Care Medicine},
pages = {1515--1524},
title = {PCSK6 and survival in idiopathic pulmonary fibrosis},
url = {},
volume = {207},
year = {2023}

RIS format (EndNote, RefMan)

AB - RATIONALE: Idiopathic pulmonary fibrosis (IPF) is a devastating disease characterized by limited treatment options and high mortality. A better understanding of the molecular drivers of IPF progression is needed. OBJECTIVE: To identify and validate molecular determinants of IPF survival. METHODS: A staged genome-wide association study (GWAS) was performed using paired genomic and survival data. Stage I cases were drawn from centers across the US and Europe and stage II cases from Vanderbilt University. Cox proportional hazards regression was used to identify gene variants associated with differential transplant-free survival (TFS). Stage I variants with nominal significance (p<5x10-5) were advanced for stage II testing and meta-analyzed to identify those reaching genome-wide significance (p<5x10-8). Downstream analyses were performed for genes and proteins associated with variants reaching genome-wide significance. MAIN RESULTS: After quality controls, 1481 stage I cases and 397 stage II cases were included in the analysis. After filtering, 9,075,629 variants were tested in stage I, with 158 meeting advancement criteria. Four variants associated with TFS with consistent effect direction were identified in stage II, including one in an intron of proprotein convertase subtilisin/kexin type 6 (PCSK6) reaching genome-wide significance (HR 4.11; 95%CI 2.54-6.67; p=9.45x10-9). PCSK6 protein was highly expressed in IPF lung parenchyma. PCSK6 lung staining intensity, peripheral blood gene expression and plasma concentration were associated with reduced transplant-free survival. CONCLUSIONS: We identified four novel variants associated with IPF survival, including one in PCSK6 that reached genome-wide significance. Downstream analyses suggested that PCSK6 protein plays a potentially important role in IPF progression. This article is open access and distributed under the terms of the Creative Commons Attribution 4.0 International License (
AU - Oldham,JM
AU - Allen,RJ
AU - Lorenzo-Salazar,JM
AU - Molyneaux,PL
AU - Ma,S-F
AU - Joseph,C
AU - Kim,JS
AU - Guillen-Guio,B
AU - Hernández-Beeftink,T
AU - Kropski,JA
AU - Huang,Y
AU - Lee,CT
AU - Adegunsoye,A
AU - Pugashetti,JV
AU - Linderholm,AL
AU - Vo,V
AU - Strek,ME
AU - Jou,J
AU - Muñoz-Barrera,A
AU - Rubio-Rodriguez,LA
AU - Hubbard,R
AU - Hirani,N
AU - Whyte,MKB
AU - Hart,S
AU - Nicholson,AG
AU - Lancaster,L
AU - Parfrey,H
AU - Rassl,D
AU - Wallace,W
AU - Valenzi,E
AU - Zhang,Y
AU - Mychaleckyj,J
AU - Stockwell,A
AU - Kaminski,N
AU - Wolters,PJ
AU - Molina-Molina,M
AU - Banovich,NE
AU - Fahy,WA
AU - Martinez,FJ
AU - Hall,IP
AU - Tobin,MD
AU - Maher,TM
AU - Blackwell,TS
AU - Yaspan,BL
AU - Jenkins,RG
AU - Flores,C
AU - Wain,LV
AU - Noth,I
DO - 10.1164/rccm.202205-0845OC
EP - 1524
PY - 2023///
SN - 1073-449X
SP - 1515
TI - PCSK6 and survival in idiopathic pulmonary fibrosis
T2 - American Journal of Respiratory and Critical Care Medicine
UR -
UR -
UR -
UR -
VL - 207
ER -