Genetic influences on epilepsy outcomes: A whole-exome sequencing and health care records data linkage study.

Autor: Fonferko-Shadrach B; Faculty of Medicine, Health, & Life Science, Swansea University Medical School, Swansea, UK., Lacey AS; Faculty of Medicine, Health, & Life Science, Swansea University Medical School, Swansea, UK., Strafford H; Faculty of Medicine, Health, & Life Science, Swansea University Medical School, Swansea, UK., Jones C; Faculty of Medicine, Health, & Life Science, Swansea University Medical School, Swansea, UK., Baker M; Swansea Bay University Health Board, Swansea, UK., Powell R; Faculty of Medicine, Health, & Life Science, Swansea University Medical School, Swansea, UK.; Swansea Bay University Health Board, Swansea, UK., Akbari A; Faculty of Medicine, Health, & Life Science, Swansea University Medical School, Swansea, UK., Lyons RA; Faculty of Medicine, Health, & Life Science, Swansea University Medical School, Swansea, UK., Ford D; Faculty of Medicine, Health, & Life Science, Swansea University Medical School, Swansea, UK., Thompson S; Faculty of Medicine, Health, & Life Science, Swansea University Medical School, Swansea, UK., Jones KH; Faculty of Medicine, Health, & Life Science, Swansea University Medical School, Swansea, UK., Chung SK; Faculty of Medicine, Health, & Life Science, Swansea University Medical School, Swansea, UK.; Brain & Mind Centre, University of Sydney, Camperdown, New South Wales, Australia.; Kids Research, Children's Hospital at Westmead, Sydney, New South Wales, Australia., Pickrell WO; Faculty of Medicine, Health, & Life Science, Swansea University Medical School, Swansea, UK.; Swansea Bay University Health Board, Swansea, UK., Rees MI; Faculty of Medicine, Health, & Life Science, Swansea University Medical School, Swansea, UK.; Faculty of Medicine & Health, University of Sydney, Camperdown, New South Wales, Australia.
Jazyk: angličtina
Zdroj: Epilepsia [Epilepsia] 2023 Nov; Vol. 64 (11), pp. 3099-3108. Date of Electronic Publication: 2023 Sep 15.
DOI: 10.1111/epi.17766
Abstrakt: 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.
(© 2023 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)
Databáze: MEDLINE
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