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Title: Novel idiopathic pulmonary fibrosis susceptibility variants revealed by deep sequencing
Authors: Lorenzo-Salazar, Jose M.
Ma, Shwu-Fan
Jou, Jonathan
Hou, Pei-Chi
Guillen-Guio, Beatriz
Allen, Richard J.
Jenkins, R. Gisli
Wain, Louise V.
Oldham, Justin M.
Noth, Imre
Flores, Carlos
First Published: 2019
Publisher: European Respiratory Society
Citation: ERJ Open Research, 2019, In Press
Abstract: Background: Specific common and rare single nucleotide variants (SNVs) increase the likelihood of developing sporadic idiopathic pulmonary fibrosis (IPF). We performed target enriched sequencing on three loci previously identified by a genome-wide association study to gain a deeper understanding of the full spectrum of IPF genetic risk and performed a two-stage case-control association study. Methods: A total of 1.7 Mb of DNA from 181 IPF patients was deep sequenced (100X) across 11p15.5, 14q21.3, and 17q21.31 loci. Comparisons were performed against 501 unrelated controls and replication studies were assessed in 3,968 subjects. Results: Thirty-six SNVs were associated with IPF susceptibility in the discovery stage (p<5.0x10-8). After meta-analysis, the strongest association corresponded to rs35705950 (p=9.27x10-57) located upstream from the mucin 5B (MUC5B) gene. Additionally, a novel association was found for two co-inherited low-frequency SNVs (<5%) in MUC5AC gene, predicting a missense amino acid change in mucin 5AC (lowest p=2.27x10-22). Conditional and haplotype analyses in 11p15.5 supported the existence of additional contribution of MUC5AC variants to IPF risk. Conclusions: This study reinforces the significant IPF associations of these loci and implicates MUC5AC as another key player in IPF susceptibility.
ISSN: 2312-0541
Links: TBA
Embargo on file until: 1-Jan-10000
Version: Post-print
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © 2019, European Respiratory Society. Deposited with reference to the publisher’s open access archiving policy. (
Description: The file associated with this record is under embargo until publication, in accordance with the publisher's self-archiving policy. The full text may be available through the publisher links provided above.
Appears in Collections:Published Articles, Dept. of Health Sciences

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