作者
Christiaan C Veerman, Svitlana Podliesna, Rafik Tadros, Elisabeth M Lodder, Isabella Mengarelli, Berend De Jonge, Leander Beekman, Julien Barc, Ronald Wilders, Arthur AM Wilde, Bastiaan J Boukens, Ruben Coronel, Arie O Verkerk, Carol Ann Remme, Connie R Bezzina
发表日期
2017/8/18
期刊
Circulation research
卷号
121
期号
5
页码范围
537-548
出版商
Lippincott Williams & Wilkins
简介
Rationale:
Genome-wide association studies previously identified an association of rs9388451 at chromosome 6q22.3 (near HEY2) with Brugada syndrome. The causal gene and underlying mechanism remain unresolved.
Objective:
We used an integrative approach entailing transcriptomic studies in human hearts and electrophysiological studies in Hey2+/− (Hey2 heterozygous knockout) mice to dissect the underpinnings of the 6q22.31 association with Brugada syndrome.
Methods and Results:
We queried expression quantitative trait locus data acquired in 190 human left ventricular samples from the genotype-tissue expression consortium for cis-expression quantitative trait locus effects of rs9388451, which revealed an association between Brugada syndrome risk allele dosage and HEY2 expression (β=+0.159; P=0.0036). In the same transcriptomic data, we conducted genome-wide coexpression analysis for …
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CC Veerman, S Podliesna, R Tadros, EM Lodder… - Circulation research, 2017