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Identification of a missense variant in SPDL1 associated with idiopathic pulmonary fibrosis
- Source :
- Communications Biology, Vol 4, Iss 1, Pp 1-8 (2021), Communications Biology
- Publication Year :
- 2021
- Publisher :
- Nature Research, 2021.
-
Abstract
- Idiopathic pulmonary fibrosis (IPF) is a fatal disorder characterised by progressive, destructive lung scarring. Despite substantial progress, the genetic determinants of this disease remain incompletely defined. Using whole genome and whole exome sequencing data from 752 individuals with sporadic IPF and 119,055 UK Biobank controls, we performed a variant-level exome-wide association study (ExWAS) and gene-level collapsing analyses. Our variant-level analysis revealed a novel association between a rare missense variant in SPDL1 and IPF (NM_017785.5:g.169588475 G > A p.Arg20Gln; p = 2.4 × 10−7, odds ratio = 2.87, 95% confidence interval: 2.03–4.07). This signal was independently replicated in the FinnGen cohort, which contains 1028 cases and 196,986 controls (combined p = 2.2 × 10−20), firmly associating this variant as an IPF risk allele. SPDL1 encodes Spindly, a protein involved in mitotic checkpoint signalling during cell division that has not been previously described in fibrosis. To the best of our knowledge, these results highlight a novel mechanism underlying IPF, providing the potential for new therapeutic discoveries in a disease of great unmet need.<br />Ryan Dhindsa et al. conducted an exome-wide association study to identify a rare variant in SPDL1 as a risk factor for idiopathic pulmonary fibrosis (IPF). Their findings implicate mitotic checkpoint signalling as a new mechanism underlying IPF.
- Subjects :
- 0301 basic medicine
Oncology
Male
Life Sciences & Biomedicine - Other Topics
FinnGen Consortium
Medicine (miscellaneous)
Cell Cycle Proteins
Disease
Idiopathic pulmonary fibrosis
0302 clinical medicine
Fibrosis
Missense mutation
Biology (General)
Exome sequencing
respiratory system
humanities
Multidisciplinary Sciences
medicine.anatomical_structure
Phenotype
030220 oncology & carcinogenesis
Science & Technology - Other Topics
Female
General Agricultural and Biological Sciences
Life Sciences & Biomedicine
medicine.medical_specialty
QH301-705.5
Mutation, Missense
General Biochemistry, Genetics and Molecular Biology
Article
03 medical and health sciences
Internal medicine
Exome Sequencing
medicine
Humans
Genetic Predisposition to Disease
Risk factor
Biology
Aged
Genetic association study
Respiratory tract diseases
Lung
Science & Technology
business.industry
Odds ratio
medicine.disease
Idiopathic Pulmonary Fibrosis
respiratory tract diseases
030104 developmental biology
Case-Control Studies
business
Genome-Wide Association Study
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Communications Biology, Vol 4, Iss 1, Pp 1-8 (2021), Communications Biology
- Accession number :
- edsair.doi.dedup.....400e1ca896fef45197cb0cae551425f5