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

Autor: Wu Y; Department of Neurology, West China Hospital of Sichuan University, Chengdu, Sichuan, People's Republic of China., Bayrak CS; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Dong B; Department of Neurology, West China Hospital of Sichuan University, Chengdu, Sichuan, People's Republic of China., He S; Department of Neurology, West China Hospital of Sichuan University, Chengdu, Sichuan, People's Republic of China., Stenson PD; Institute of Medical Genetics, Cardiff University, Cardiff, UK., Cooper DN; Institute of Medical Genetics, Cardiff University, Cardiff, UK., Itan Y; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA. yuval.itan@mssm.edu.; Icahn School of Medicine at Mount Sinai, The Charles Bronfman Institute for Personalized Medicine, New York, NY, USA. yuval.itan@mssm.edu., Chen L; Department of Neurology, West China Hospital of Sichuan University, Chengdu, Sichuan, People's Republic of China. leilei_25@126.com.
Jazyk: angličtina
Zdroj: Human genetics [Hum Genet] 2023 Feb; Vol. 142 (2), pp. 275-288. Date of Electronic Publication: 2022 Nov 09.
DOI: 10.1007/s00439-022-02502-4
Abstrakt: 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.
(© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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