Bayesian modeling to predict malignant hyperthermia susceptibility and pathogenicity of RYR1, CACNA1S and STAC3 variants
dc.contributor.author | Sadhasivam, Senthilkumar | |
dc.contributor.author | Henker, Richard A. | |
dc.contributor.author | Brandom, Barbara W. | |
dc.contributor.author | McAuliffe, John J. | |
dc.contributor.department | Anesthesia, School of Medicine | en_US |
dc.date.accessioned | 2021-05-28T23:16:54Z | |
dc.date.available | 2021-05-28T23:16:54Z | |
dc.date.issued | 2019-09-27 | |
dc.description.abstract | Aim: Identify variants in RYR1, CACNA1S and STAC3, and predict malignant hyperthermia (MH) pathogenicity using Bayesian statistics in individuals clinically treated as MH susceptible (MHS). Materials & methods: Whole exome sequencing including RYR1, CACNA1S and STAC3 performed on 64 subjects with: MHS; suspected MH event or first-degree relative; and MH negative. Variant pathogenicity was estimated using in silico analysis, allele frequency and prior data to calculate Bayesian posterior probabilities. Results: Bayesian statistics predicted CACNA1S variant p.Thr1009Lys and RYR1 variants p.Ser1728Phe and p.Leu4824Pro are likely pathogenic, and novel STAC3 variant p.Met187Thr has uncertain significance. Nearly a third of MHS subjects had only benign variants. Conclusion: Bayesian method provides new approach to predict MH pathogenicity of genetic variants. | en_US |
dc.identifier.citation | Sadhasivam, S., Brandom, B. W., Henker, R. A., & McAuliffe, J. J. (2019). Bayesian modeling to predict malignant hyperthermia susceptibility and pathogenicity of RYR1, CACNA1S and STAC3 variants. Pharmacogenomics, 20(14), 989–1003. https://doi.org/10.2217/pgs-2019-0055 | en_US |
dc.identifier.issn | 1462-2416 | en_US |
dc.identifier.uri | https://hdl.handle.net/1805/26071 | |
dc.language.iso | en_US | en_US |
dc.publisher | Future Medicine | en_US |
dc.relation.isversionof | 10.2217/pgs-2019-0055 | en_US |
dc.relation.journal | Pharmacogenomics | en_US |
dc.source | PMC | en_US |
dc.subject | CACNA1S | en_US |
dc.subject | contracture test | en_US |
dc.subject | exome | en_US |
dc.subject | genetic | en_US |
dc.subject | malignant hyperthermia | en_US |
dc.subject | muscle | en_US |
dc.subject | next-generation sequencing | en_US |
dc.subject | novel | en_US |
dc.subject | pathologic | en_US |
dc.subject | RYR1 | en_US |
dc.subject | STAC3 | en_US |
dc.title | Bayesian modeling to predict malignant hyperthermia susceptibility and pathogenicity of RYR1, CACNA1S and STAC3 variants | en_US |
dc.type | Article | en_US |
ul.alternative.fulltext | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7006767/ | en_US |
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