Common variants in RYR1 are associated with left ventricular hypertrophy assessed by electrocardiogram

Aims To identify the genetic risk factors that influence the development of electrocardiographic (ECG) left ventricular hypertrophy (LVH), a major risk factor for cardiovascular (CV) morbidity and mortality. Methods and results We performed a genomewide association study (GWAS) of ECG-LVH, in which the community-based Korea Association REsource (KARE) study (8432 controls and 398 cases) was analysed by Affymetrix SNP array 5.0. The GWAS results were validated in hospital-based samples (597 controls and 207 cases). Fourteen single-nucleotide polymorphisms (SNPs) in eight genetic loci (5q35.1, 6p22.3-22.1, 8q24.2, 11p15, 11q21-22.1, 14q12, 17q11.2, and 19q13.1) were associated with ECG-LVH in the original GWAS study (P < 1 × 10 ^-5). Of these SNPs, 12 were genotyped in the hospital sample. There was consistent association with the 19q13.1 region which contains RYR1 gene. The most significant SNP in the region was rs10500279, which had genomewide significance in the combined GWAS/replication sample [odds ratio 1.58 (confidence interval: 1.351.85), P 1.0 × 10 ^-8]. Mutations in RYR1, which encodes a major Ca ² channel in the skeletal muscle, have been reported to correlate with CV diseases. Conclusion We performed the first GWAS for ECG-LVH, implicating the skeletal muscle Ca ² channel protein RYR1 as a genetic risk factor. These results might increase our understanding of the development of ECG-LVH.