Journal article 588 views 69 downloads
Genetic influences on epilepsy outcomes: a whole‐exome sequencing and healthcare records data linkage study
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Ronan Lyons ,
David Ford ,
Simon Ellwood-Thompson,
Kerina Jones ,
Seo‐Kyung Chung,
Owen Pickrell ,
Mark I. Rees
Epilepsia
Swansea University Authors:
Beata Fonferko-Shadrach, Arron Lacey, Huw Strafford, Carys Jones, Ashley Akbari , Ronan Lyons , David Ford , Simon Ellwood-Thompson, Kerina Jones , Owen Pickrell
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© 2023 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy. Distributed under the terms of a Creative Commons Attribution Non Commercial 4.0 License (CC BY-NC 4.0).
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DOI (Published version): 10.1111/epi.17766
Abstract
Objective: This study was undertaken to develop a novel pathway linking genetic data with routinely collected data for people with epilepsy, and to analyze the influence of rare, deleterious genetic variants on epilepsy outcomes. Methods: We linked whole-exome sequencing (WES) data with routinely co...
| Published in: | Epilepsia |
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| ISSN: | 0013-9580 1528-1167 |
| Published: |
Wiley
2023
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| Online Access: |
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| URI: | https://cronfa.swan.ac.uk/Record/cronfa64175 |
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| Abstract: |
Objective: This study was undertaken to develop a novel pathway linking genetic data with routinely collected data for people with epilepsy, and to analyze the influence of rare, deleterious genetic variants on epilepsy outcomes. Methods: We linked whole-exome sequencing (WES) data with routinely collected primary and secondary care data and natural language processing (NLP)-derived seizure frequency information for people with epilepsy within the Secure Anonymised Information Linkage Databank. The study participants were adults who had consented to participate in the Swansea Neurology Biobank, Wales, between 2016 and 2018. DNA sequencing was carried out as part of the Epi25 collaboration. For each individual, we calculated the total number and cumulative burden of rare and predicted deleterious genetic variants and the total of rare and deleterious variants in epilepsy and drug metabolism genes. We compared these measures with the following outcomes: (1) no unscheduled hospital admissions versus unscheduled admissions for epilepsy, (2) antiseizure medication (ASM) monotherapy versus polytherapy, and (3) at least 1 year of seizure freedom versus <1 year of seizure freedom. Results: We linked genetic data for 107 individuals with epilepsy (52% female) to electronic health records. Twenty-six percent had unscheduled hospital admissions, and 70% were prescribed ASM polytherapy. Seizure frequency information was linked for 100 individuals, and 10 were seizure-free. There was no significant difference between the outcome groups in terms of the exome-wide and gene-based burden of rare and deleterious genetic variants. Significance: We successfully uploaded, annotated, and linked genetic sequence data and NLP-derived seizure frequency data to anonymized health care records in this proof-of-concept study. We did not detect a genetic influence on real-world epilepsy outcomes, but our study was limited by a small sample size. Future studies will require larger (WES) data to establish genetic variant contribution to epilepsy outcomes. |
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| Keywords: |
Antiseizure medication, genetic variant burden, natural language processing, seizure frequency, unscheduled admission |
| College: |
Faculty of Medicine, Health and Life Sciences |
| Funders: |
This work was supported by staff funded as part of the Wales Gene Park, an infrastructure support group funded by the Welsh Government through Health and Care Research Wales. The views expressed are those of the authors and not necessarily those of Health and Care Research Wales or the Welsh Government. We thank and acknowledge our colleagues in the Broad Institute and the Epi25 collaborative (http://epi-25.org/). Epi25 regards this work as a local secondary study limited to repatriated WES data. No other submitting Epi25 sites were included due to the limited study access to Wales National Health Service health care data. This study used anonymized data held in the Secure Anonymised Information Linkage Databank. We would like to acknowledge all the data providers who make anonymized data available for research. Open access publishing facilitated by The University of Sydney, as part of the Wiley - The University of Sydney agreement via the Council of Australian University Librarians. |