title: Identification of three novel genetic variations associated with electrocardiographic traits (QRS duration and PR interval) in East Asians.
abstract: 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).
authors.affiliation: Division of Epidemiology and Health Index, Center for Genome Science, Korea Centers for Disease Control and Prevention, Chungcheongbuk-do 363-951, Korea.
authors.forename: Kyung-Won
authors.initials: KW
authors.lastname: Hong
authors.affiliation: Department of Biomedical Engineering, School of Medicine, Kyung Hee University, Seoul 130-701, Korea.
authors.forename: Ji Eun
authors.initials: JE
authors.lastname: Lim
authors.affiliation: Department of Internal Medicine, Inje University Ilsan Paik Hospital, Gyeonggi-do 411-706, Korea.
authors.forename: Jong Wook
authors.initials: JW
authors.lastname: Kim
authors.affiliation: Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan.
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Tabara
authors.affiliation: Center for Epidemiologic Research in Asia and, Department of Health Science, Shiga University of Medical Science, Otsu 520-2121, Japan.
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Ueshima
authors.affiliation: Department of Geriatric Medicine, Ehime University Graduate School of Medicine, Toon 791-0295, Japan and.
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Miki
authors.affiliation: Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan.
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Matsuda
authors.affiliation: Department of Biomedical Science, Hallym University, Chuncheon, Gangwon-do 200-702, Korea.
authors.forename: Yoon Shin
authors.initials: YS
authors.lastname: Cho
authors.affiliation: Division of Epidemiology and Health Index, Center for Genome Science, Korea Centers for Disease Control and Prevention, Chungcheongbuk-do 363-951, Korea, ohbs@khu.ac.kr yeonmaru@gmail.com.
authors.forename: Yeonjung
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Department of Biomedical Engineering, School of Medicine, Kyung Hee University, Seoul 130-701, Korea, ohbs@khu.ac.kr yeonmaru@gmail.com.
authors.forename: Bermseok
authors.initials: B
authors.lastname: Oh
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D001145:Arrhythmias, Cardiac / Q000208:ethnology / Q000235:genetics* / Q000503:physiopathology; D044466:Asian People; D004268:DNA-Binding Proteins / Q000235:genetics*; D004562:Electrocardiography; D005260:Female; D005787:Gene Frequency; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D019831:Sodium-Calcium Exchanger / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D009124:Muscle Proteins; C416371:PRDM16 protein, human; C574688:PRDM6 protein, human; D019831:Sodium-Calcium Exchanger; D014157:Transcription Factors; C110374:sodium-calcium exchanger 1