| Title: | Host genetic effects in pneumonia |
| Journal: | American Journal of Human Genetics |
| Published: | 13 Dec 2020 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/33357513/ |
| DOI: | https://doi.org/10.1016/j.ajhg.2020.12.010 |
| URL: | https://europepmc.org/articles/pmc7820802?pdf=render |
| Citations: | 19 (6 in last 2 years) as of 8 Aug 2024 |
Publication 5150
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Abstract
Given the coronavirus disease 2019 (COVID-19) pandemic, investigations into host susceptibility to infectious diseases and downstream sequelae have never been more relevant. Pneumonia is a lung disease that can cause respiratory failure and hypoxia and is a common complication of infectious diseases, including COVID-19. Few genome-wide association studies (GWASs) of host susceptibility and severity of pneumonia have been conducted. We performed GWASs of pneumonia susceptibility and severity in the Vanderbilt University biobank (BioVU) with linked electronic health records (EHRs), including Illumina Expanded Multi-Ethnic Global Array (MEGAEX)-genotyped European ancestry (EA, n= 69,819) and African ancestry (AA, n = 15,603) individuals. Two regions of large effect were identified: the CFTR locus in EA (rs113827944; OR = 1.84, p value = 1.2 × 10-36) and HBB in AA (rs334 [p.Glu7Val]; OR = 1.63, p value = 3.5 × 10-13). Mutations in these genes cause cystic fibrosis (CF) and sickle cell disease (SCD), respectively. After removing individuals diagnosed with CF and SCD, we assessed heterozygosity effects at our lead variants. Further GWASs after removing individuals with CF uncovered an additional association in R3HCC1L (rs10786398; OR = 1.22, p value = 3.5 × 10-8), which was replicated in two independent datasets: UK Biobank (n = 459,741) and 7,985 non-overlapping BioVU subjects, who are genotyped on arrays other than MEGAEX. This variant was also validated in GWASs of COVID-19 hospitalization and lung function. Our results highlight the importance of the host genome in infectious disease susceptibility and severity and offer crucial insight into genetic effects that could potentially influence severity of COVID-19 sequelae.</p>
21 Keywords
- Bronchitis
- COVID-19
- Cystic Fibrosis Transmembrane Conductance Regulator
- Databases, Genetic
- Electronic Health Records
- Female
- Genome-Wide Association Study
- Genotype
- Hemoglobins
- Host-Pathogen Interactions
- Humans
- Inpatients
- Linkage Disequilibrium
- Male
- Outpatients
- Pneumonia, Viral
- Polymorphism, Single Nucleotide
- Principal Component Analysis
- Pulmonary Disease, Chronic Obstructive
- Reproducibility of Results
- United Kingdom
18 Authors
- Hung-Hsin Chen
- Douglas M. Shaw
- Lauren E. Petty
- Misa Graff
- Ryan J. Bohlender
- Hannah G. Polikowsky
- Xue Zhong
- Daeeun Kim
- Victoria L. Buchanan
- Michael H. Preuss
- Megan M. Shuey
- Ruth J.F. Loos
- Chad D. Huff
- Nancy J. Cox
- Julie A. Bastarache
- Lisa Bastarache
- Kari E. North
- Jennifer E. Below
Enabling scientific discoveries that improve human health