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; Michael F Buckley; Mark J Cowley; Tony Roscioli

doi:10.1038/gim.2018.39

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. DingerMichael F Buckley, Mark J Cowley, Tony Roscioli

Research output: Contribution to journal › Article › peer-review

152 Citations (Scopus)

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%.

Original language	English
Pages (from-to)	1564-1574
Number of pages	11
Journal	Genetics in medicine : official journal of the American College of Medical Genetics
Volume	20
Issue number	12
Early online date	29 Mar 2018
DOIs	https://doi.org/10.1038/gim.2018.39
Publication status	Published - 1 Dec 2018
Externally published	Yes

Keywords

cost-effectiveness
diagnosis
exome
genomics
Mendelian

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10.1038/gim.2018.39

Cite this

Ewans, L. J., Schofield, D., Shrestha, R., Zhu, Y., Gayevskiy, V., Ying, K., Walsh, C., Lee, E., Kirk, E. P., Colley, A., Ellaway, C., Turner, A., Mowat, D., Worgan, L., Freckmann, M.-L., Lipke, M., Sachdev, R., Miller, D., Field, M., ... 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, 20(12), 1564-1574. https://doi.org/10.1038/gim.2018.39

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

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 et al.
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 journal › Article › peer-review

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T1 - Whole-exome sequencing reanalysis at 12 months boosts diagnosis and is cost-effective when applied early in Mendelian disorders

AU - Ewans, Lisa J

AU - Schofield, Deborah

AU - Shrestha, Rupendra

AU - Zhu, Ying

AU - Gayevskiy, Velimir

AU - Ying, Kevin

AU - Walsh, Corrina

AU - Lee, Eric

AU - Kirk, Edwin P

AU - Colley, Alison

AU - Ellaway, Carolyn

AU - Turner, Anne

AU - Mowat, David

AU - Worgan, Lisa

AU - Freckmann, Mary-Louise

AU - Lipke, Michelle

AU - Sachdev, Rani

AU - Miller, David

AU - Field, Michael

AU - Dinger, Marcel E.

AU - Buckley, Michael F

AU - Cowley, Mark J

AU - Roscioli, Tony

PY - 2018/12/1

Y1 - 2018/12/1

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

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Keywords

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The Economic and Psychosocial Impact of Caring for families affected by intellectual disability (THE EPIC-ID Study)

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

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The Economic and Psychosocial Impact of Caring for families affected by intellectual disability (THE EPIC-ID Study)

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