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| PMID |
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| TITLE |
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| Genetic Susceptibility to Pneumonia: A GWAS Meta-Analysis Between the UK Biobank and FinnGen. |
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| ABSTRACT |
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| Pneumonia is a respiratory condition with complex etiology. Host genetic variation is thought to contribute to individual differences in susceptibility and symptom manifestation. Here, we analyze pneumonia data from the UK Biobank (14,780 cases and 439,096 controls) and FinnGen (9980 cases and 86,519 controls) and perform a genomewide association study meta-analysis. We use gene-based tests, colocalization, genetic correlation, latent causal variable (LCV) and polygenic prediction in an independent Australian sample (N = 5595) to draw insights into the etiology of pneumonia risk. We identify two independent loci on chromosome 15 (lead single-nucleotide polymorphisms rs2009746 and rs76474922) to be associated with pneumonia (p < 5e-8). Gene-based tests revealed 18 genes in chromosomes 15, 16 and 9, including IL127, PBX3, ApoB receptor (APOBR) and smoking related genes CHRNA3/5, statistically associated with pneumonia. We observed genetic correlations between pneumonia and cardiorespiratory, psychiatric and inflammatory related traits. LCV analysis suggests a strong genetic causal relationship with cardiovascular health phenotypes. Polygenic risk scores for pneumonia significantly predicted self-reported pneumonia in an independent sample, albeit with a small effect size (OR = 1.11 95% CI [1.04, 1.19], p < .05). Sensitivity analyses suggested the associations in chromosome 15 are mediated by smoking history, but the associations in chromosomes 16 and 9, and polygenic prediction were robust to adjustment for smoking. Altogether, our results highlight common genetic variants, genes and potential pathways that contribute to individual differences in susceptibility to pneumonia, and advance our understanding of the genetic factors underlying heterogeneity in respiratory medical outcomes. |
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| DATE PUBLISHED |
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| HISTORY |
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| PUBSTATUS |
PUBSTATUSDATE |
| pubmed |
2021/08/04 06:00 |
| medline |
2021/08/04 06:00 |
| entrez |
2021/08/03 05:37 |
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| AUTHORS |
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| NAME |
COLLECTIVENAME |
LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
AFFILIATIONINFO |
| Campos AI |
|
Campos |
Adrian I |
AI |
|
Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia. |
| Kho P |
|
Kho |
Pik |
P |
|
Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. |
| Vazquez-Prada KX |
|
Vazquez-Prada |
Karla X |
KX |
|
School of Pharmacy, Pharmacy Australia Centre of Excellence, The University of Queensland, Brisbane, Queensland, Australia. |
| García-Marín LM |
|
García-Marín |
Luis M |
LM |
|
Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. |
| Martin NG |
|
Martin |
Nicholas G |
NG |
|
Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. |
| Cuéllar-Partida G |
|
Cuéllar-Partida |
Gabriel |
G |
|
Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. |
| Rentería ME |
|
Rentería |
Miguel E |
ME |
|
Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia. |
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| INVESTIGATORS |
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| JOURNAL |
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| VOLUME: 24 |
| ISSUE: 3 |
| TITLE: Twin research and human genetics : the official journal of the International Society for Twin Studies |
| ISOABBREVIATION: Twin Res Hum Genet |
| YEAR: 2021 |
| MONTH: Jun |
| DAY: |
| MEDLINEDATE: |
| SEASON: |
| CITEDMEDIUM: Internet |
| ISSN: 1832-4274 |
| ISSNTYPE: Print |
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| MEDLINE JOURNAL |
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| MEDLINETA: Twin Res Hum Genet |
| COUNTRY: England |
| ISSNLINKING: 1832-4274 |
| NLMUNIQUEID: 101244624 |
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| PUBLICATION TYPE |
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| PUBLICATIONTYPE TEXT |
| Journal Article |
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| COMMENTS AND CORRECTIONS |
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| GRANTS |
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| GENERAL NOTE |
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| KEYWORDS |
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| KEYWORD |
| FinnGen |
| GWAS |
| PRS |
| Pneumonia |
| UK Biobank |
| genomewide association study |
| host response genetics |
| polygenic risk scores |
| respiratory infection |
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| MESH HEADINGS |
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| SUPPLEMENTARY MESH |
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| GENE SYMBOLS |
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| CHEMICALS |
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| OTHER ID's |
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