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Identifying shared genetic factors underlying epilepsy and congenital heart disease in Europeans

Wu, Yiming, Bayrak, Cigdem Sevim, Dong, Bosi, He, Shixu, Stenson, Peter D., Cooper, David N. ORCID:, Itan, Yuval and Chen, Lei 2023. Identifying shared genetic factors underlying epilepsy and congenital heart disease in Europeans. Human Genetics 142 , pp. 275-288. 10.1007/s00439-022-02502-4

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Epilepsy (EP) and congenital heart disease (CHD) are two apparently unrelated diseases that nevertheless display substantial mutual comorbidity. Thus, while congenital heart defects are associated with an elevated risk of developing epilepsy, the incidence of epilepsy in CHD patients correlates with CHD severity. Although genetic determinants have been postulated to underlie the comorbidity of EP and CHD, the precise genetic etiology is unknown. We performed variant and gene association analyses on EP and CHD patients separately, using whole exomes of genetically identified Europeans from the UK Biobank and Mount Sinai BioMe Biobank. We prioritized biologically plausible candidate genes and investigated the enriched pathways and other identified comorbidities by biological proximity calculation, pathway analyses, and gene-level phenome-wide association studies. Our variant- and gene-level results point to the Voltage-Gated Calcium Channels (VGCC) pathway as being a unifying framework for EP and CHD comorbidity. Additionally, pathway-level analyses indicated that the functions of disease-associated genes partially overlap between the two disease entities. Finally, phenome-wide association analyses of prioritized candidate genes revealed that cerebral blood flow and ulcerative colitis constitute the two main traits associated with both EP and CHD.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: Springer
ISSN: 0340-6717
Date of First Compliant Deposit: 21 December 2022
Date of Acceptance: 24 October 2022
Last Modified: 10 Nov 2023 16:59

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