- Title
- The genetic architecture of pneumonia susceptibility implicates mucin biology and a relationship with psychiatric illness
- Creator
- Reay, William R.; Geaghan, Michael P.; Cairns, Murray J.; 23andMe Research Team,
- Relation
- NHMRC. NHMRC 1121474 http://purl.org/au-research/grants/nhmrc/1121474 & 1147644 http://purl.org/au-research/grants/nhmrc/1147644
- Relation
- Nature Communications Vol. 13, Issue 1, no. 3756
- Publisher Link
- http://dx.doi.org/10.1038/s41467-022-31473-3
- Publisher
- Nature Publishing Group
- Resource Type
- journal article
- Date
- 2022
- Description
- Pneumonia remains one of the leading causes of death worldwide. In this study, we use genome-wide meta-analysis of lifetime pneumonia diagnosis (N = 391,044) to identify four association signals outside of the previously implicated major histocompatibility complex region. Integrative analyses and finemapping of these signals support clinically tractable targets, including the mucin MUC5AC and tumour necrosis factor receptor superfamily member TNFRSF1A. Moreover, we demonstrate widespread evidence of genetic overlap with pneumonia susceptibility across the human phenome, including particularly significant correlations with psychiatric phenotypes that remain significant after testing differing phenotype definitions for pneumonia or genetically conditioning on smoking behaviour. Finally, we show how polygenic risk could be utilised for precision treatment formulation or drug repurposing through pneumonia risk scores constructed using variants mapped to pathways with known drug targets. In summary, we provide insights into the genetic architecture of pneumonia susceptibility and genetics informed targets for drug development or repositioning.
- Subject
- pneumonia; genome-wide association study; MUC5AC; TNFRSF1A; SDG 3; Sustainable Development Goals
- Identifier
- http://hdl.handle.net/1959.13/1484468
- Identifier
- uon:51343
- Identifier
- ISSN:2041-1723
- Language
- eng
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