Premium
Targeted resequencing reveals genetic risks in patients with sporadic idiopathic pulmonary fibrosis
Author(s) -
Deng Yanhan,
Li Zongzhe,
Liu Juan,
Wang Zheng,
Cao Yanyan,
Mou Yong,
Fu Bohua,
Mo Biwen,
Wei Jianghong,
Cheng Zhenshun,
Luo Liman,
Li Jingping,
Shu Ying,
Wang Xiaomei,
Luo Guangwei,
Yang Shuo,
Wang Yingnan,
Zhu Jing,
Yang Jingping,
Wu Ming,
Xu Xuyan,
Ge Renying,
Chen Xueqin,
Peng Qingzhen,
Wei Guang,
Li Yaqing,
Yang Hua,
Fang Shirong,
Zhang Xiaoju,
Xiong Weining
Publication year - 2018
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.23566
Subject(s) - biology , idiopathic pulmonary fibrosis , sanger sequencing , missense mutation , single nucleotide polymorphism , candidate gene , bioinformatics , medicine , genetics , gene , genotype , mutation , lung
Idiopathic pulmonary fibrosis (IPF) is a genetic heterogeneous disease with high mortality and poor prognosis. However, a large fraction of genetic cause remains unexplained, especially in sporadic IPF (∼80% IPF). By systemically reviewing related literature and potential pathogenic pathways, 92 potentially IPF‐related genes were selected and sequenced in genomic DNAs from 253 sporadic IPF patients and 125 matched health controls using targeted massively parallel next‐generation sequencing. The identified risk variants were confirmed by Sanger sequencing. We identified two pathogenic and 10 loss‐of‐function (LOF) candidate variants, accounting for 4.74% (12 out of 253) of all the IPF cases. In burden tests, rare missense variants in three genes ( CSF3R , DSP , and LAMA3 ) were identified that have a statistically significant relationship with IPF. Four common SNPs (rs3737002, rs2296160, rs1800470, and rs35705950) were observed to be statistically associated with increased risk of IPF. In the cumulative risk model, high risk subjects had 3.47‐fold (95%CI: 2.07–5.81, P = 2.34 × 10 −6 ) risk of developing IPF compared with low risk subjects. We drafted a comprehensive map of genetic risks (including both rare and common candidate variants) in patients with IPF, which could provide insights to help in understanding mechanisms, providing genetic diagnosis, and predicting risk for IPF.