Identification of three novel genetic variations associated with electrocardiographic traits (QRS duration and PR interval) in East Asians

• Published in: Human molecular genetics Vol. 23; no. 24; pp. 6659 - 6667
• Main Authors: Hong, Kyung-Won, Lim, Ji Eun, Kim, Jong Wook, Tabara, Yasuharu, Ueshima, Hirotsugu, Miki, Tetsuro, Matsuda, Fumihiko, Cho, Yoon Shin, Kim, Yeonjung, Oh, Bermseok
• Format: Journal Article
• Language: English
• Published: England 15.12.2014
• Subjects: Adult; Aged; Alleles; Arrhythmias, Cardiac - ethnology; Arrhythmias, Cardiac - genetics; Arrhythmias, Cardiac - physiopathology; Asian Continental Ancestry Group; DNA-Binding Proteins - genetics; Electrocardiography; Female; Gene Frequency; Genome-Wide Association Study; Humans; Male; Middle Aged; Muscle Proteins - genetics; Polymorphism, Single Nucleotide; Quantitative Trait Loci; Sodium-Calcium Exchanger - genetics; Transcription Factors - genetics
• ISSN: 0964-6906; 1460-2083
• DOI: 10.1093/hmg/ddu374

The electrocardiogram has several advantages in detecting cardiac arrhythmia-it is readily available, noninvasive and cost-efficient. Recent genome-wide association studies have identified single-nucleotide polymorphisms that are associated with electrocardiogram measures. We performed a genome-wide association study using Korea Association Resource data for the discovery phase (Phase 1, n = 6805) and two consecutive replication studies in Japanese populations (Phase 2, n = 2285; Phase 3, n = 5010) for QRS duration and PR interval. Three novel loci were identified: rs2483280 (PRDM16 locus) and rs335206 (PRDM6 locus) were associated with QRS duration, and rs17026156 (SLC8A1 locus) correlated with PR interval. PRDM16 was recently identified as a causative gene of left ventricular non-compaction and dilated cardiomyopathy in 1p36 deletion syndrome, which is characterized by heart failure, arrhythmia and sudden cardiac death. Thus, our finding that a PRDM16 SNP is linked to QRS duration strongly implicates PRDM16 in cardiac function. In addition, C allele of rs17026156 increases PR interval (beta ± SE, 2.39 ± 0.40 ms) and exists far more frequently in East Asians (0.46) than in Europeans and Africans (0.05 and 0.08, respectively).