Whole-exome sequencing reanalysis at 12 months boosts diagnosis and is cost-effective when applied early in Mendelian disorders

Lisa J Ewans, Deborah Schofield, Rupendra Shrestha, Ying Zhu, Velimir Gayevskiy, Kevin Ying, Corrina Walsh, Eric Lee, Edwin P Kirk, Alison Colley, Carolyn Ellaway, Anne Turner, David Mowat, Lisa Worgan, Mary-Louise Freckmann, Michelle Lipke, Rani Sachdev, David Miller, Michael Field, Marcel E. Dinger & 3 others Michael F Buckley, Mark J Cowley, Tony Roscioli

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Purpose: Whole-exome sequencing (WES) has revolutionized Mendelian diagnostics, however, there is no consensus on the timing of data review in undiagnosed individuals and only preliminary data on the cost-effectiveness of this technology. We aimed to assess the utility of WES data reanalysis for diagnosis in Mendelian disorders and to analyze the cost-effectiveness of this technology compared with a traditional diagnostic pathway. 

Methods: WES was applied to a cohort of 54 patients from 37 families with a variety of Mendelian disorders to identify the genetic etiology. Reanalysis was performed after 12 months with an improved WES diagnostic pipeline. A comparison was made between costs of a modeled WES pathway and a traditional diagnostic pathway in a cohort with intellectual disability (ID). 

Results: Reanalysis of WES data at 12 months improved diagnostic success from 30 to 41% due to interim publication of disease genes, expanded phenotype data from referrer, and an improved bioinformatics pipeline. Cost analysis on the ID cohort showed average cost savings of US$586 (AU$782) for each additional diagnosis.

Conclusion: Early application of WES in Mendelian disorders is cost-effective and reanalysis of an undiagnosed individual at a 12-month time point increases total diagnoses by 11%.

LanguageEnglish
Pages1564-1574
Number of pages11
JournalGenetics in medicine : official journal of the American College of Medical Genetics
Volume20
Issue number12
Early online date29 Mar 2018
DOIs
Publication statusPublished - 1 Dec 2018
Externally publishedYes

Fingerprint

Exome
Costs and Cost Analysis
Intellectual Disability
Cost-Benefit Analysis
Technology
Cost Savings
Computational Biology
Publications
Consensus
Phenotype

Keywords

  • cost-effectiveness
  • diagnosis
  • exome
  • genomics
  • Mendelian

Cite this

Ewans, Lisa J ; Schofield, Deborah ; Shrestha, Rupendra ; Zhu, Ying ; Gayevskiy, Velimir ; Ying, Kevin ; Walsh, Corrina ; Lee, Eric ; Kirk, Edwin P ; Colley, Alison ; Ellaway, Carolyn ; Turner, Anne ; Mowat, David ; Worgan, Lisa ; Freckmann, Mary-Louise ; Lipke, Michelle ; Sachdev, Rani ; Miller, David ; Field, Michael ; Dinger, Marcel E. ; Buckley, Michael F ; Cowley, Mark J ; Roscioli, Tony. / Whole-exome sequencing reanalysis at 12 months boosts diagnosis and is cost-effective when applied early in Mendelian disorders. In: Genetics in medicine : official journal of the American College of Medical Genetics. 2018 ; Vol. 20, No. 12. pp. 1564-1574.
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abstract = "Purpose: Whole-exome sequencing (WES) has revolutionized Mendelian diagnostics, however, there is no consensus on the timing of data review in undiagnosed individuals and only preliminary data on the cost-effectiveness of this technology. We aimed to assess the utility of WES data reanalysis for diagnosis in Mendelian disorders and to analyze the cost-effectiveness of this technology compared with a traditional diagnostic pathway. Methods: WES was applied to a cohort of 54 patients from 37 families with a variety of Mendelian disorders to identify the genetic etiology. Reanalysis was performed after 12 months with an improved WES diagnostic pipeline. A comparison was made between costs of a modeled WES pathway and a traditional diagnostic pathway in a cohort with intellectual disability (ID). Results: Reanalysis of WES data at 12 months improved diagnostic success from 30 to 41{\%} due to interim publication of disease genes, expanded phenotype data from referrer, and an improved bioinformatics pipeline. Cost analysis on the ID cohort showed average cost savings of US$586 (AU$782) for each additional diagnosis.Conclusion: Early application of WES in Mendelian disorders is cost-effective and reanalysis of an undiagnosed individual at a 12-month time point increases total diagnoses by 11{\%}.",
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Ewans, LJ, Schofield, D, Shrestha, R, Zhu, Y, Gayevskiy, V, Ying, K, Walsh, C, Lee, E, Kirk, EP, Colley, A, Ellaway, C, Turner, A, Mowat, D, Worgan, L, Freckmann, M-L, Lipke, M, Sachdev, R, Miller, D, Field, M, Dinger, ME, Buckley, MF, Cowley, MJ & Roscioli, T 2018, 'Whole-exome sequencing reanalysis at 12 months boosts diagnosis and is cost-effective when applied early in Mendelian disorders', Genetics in medicine : official journal of the American College of Medical Genetics, vol. 20, no. 12, pp. 1564-1574. https://doi.org/10.1038/gim.2018.39

Whole-exome sequencing reanalysis at 12 months boosts diagnosis and is cost-effective when applied early in Mendelian disorders. / Ewans, Lisa J; Schofield, Deborah; Shrestha, Rupendra; Zhu, Ying; Gayevskiy, Velimir; Ying, Kevin; Walsh, Corrina; Lee, Eric; Kirk, Edwin P; Colley, Alison; Ellaway, Carolyn; Turner, Anne; Mowat, David; Worgan, Lisa; Freckmann, Mary-Louise; Lipke, Michelle; Sachdev, Rani; Miller, David; Field, Michael; Dinger, Marcel E.; Buckley, Michael F; Cowley, Mark J; Roscioli, Tony.

In: Genetics in medicine : official journal of the American College of Medical Genetics, Vol. 20, No. 12, 01.12.2018, p. 1564-1574.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Gayevskiy, Velimir

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