title: Genome-wide association study of electrocardiographic parameters identifies a new association for PR interval and confirms previously reported associations.
abstract: Previous reports have described several associations of PR, QRS, QT and heart rate with genomic variations by genome-wide association studies (GWASs). In the present study, we examined the association of ∼2.5 million SNPs from 2994 Japanese healthy volunteers obtained from the JPDSC database with electrocardiographic parameters. We confirmed associations of PR interval, QRS duration and QT interval in individuals of Japanese ancestry with 11 of the 45 SNPs (6 of 20 for QT, 5 of 19 for PR and 0 of 6 for QRS) observed among individuals of European, African and Asian (Indian and Korean) ancestries. Those results indicate that many of the electrocardiographic associations with genes are shared by different ethnic groups including Japanese. Possible novel associations found in this study were validated by Korean data. As a result, we identified a novel association of SNP rs4952632[G] (maps near SLC8A1, sodium-calcium exchanger) (P = 7.595 × 10(-6)) with PR interval in Japanese individuals, and replication testing among Koreans confirmed the association of the same SNP with prolonged PR interval. Meta-analysis of the Japanese and Korean datasets demonstrated highly significant associations of SNP rs4952632[G] with a 2.325-ms (95% CI, 1.693-2.957 ms) longer PR interval per minor allele copy (P = 5.598 × 10(-13)). Cell-type-specific SLC8A1 knockout mice have demonstrated a regulatory role of sodium-calcium exchanger in automaticity and conduction in sinoatrial node, atrium and atrioventricular node. Our findings support a functional role of sodium-calcium exchanger in human atrial and atrioventricular nodal conduction as suggested by genetically modified mouse models.
authors: Department of Cardiology, Keio University School of Medicine, Tokyo, Japan, msano@a8.keio.jp.
authors: Motoaki
authors: M
authors: Sano
authors: StaGen Co. Ltd., Tokyo, Japan.
authors: Shigeo
authors: S
authors: Kamitsuji
authors: StaGen Co. Ltd., Tokyo, Japan.
authors: Naoyuki
authors: N
authors: Kamatani
authors: Center for Genome Science, Korea National Institute of Health, Korea Centers for Disease Control and Prevention, Cheongwon 363-951, Korea and.
authors: Kyung-Won
authors: KW
authors: Hong
authors: Center for Genome Science, Korea National Institute of Health, Korea Centers for Disease Control and Prevention, Cheongwon 363-951, Korea and.
authors: Bok-Ghee
authors: BG
authors: Han
authors: Center for Genome Science, Korea National Institute of Health, Korea Centers for Disease Control and Prevention, Cheongwon 363-951, Korea and.
authors: Yeonjung
authors: Y
authors: Kim
authors: Department of Internal Medicine, Inje University Ilsan Paik Hospital, Goyang, Korea.
authors: Jong Wook
authors: JW
authors: Kim
authors: Department of Cardiology, Keio University School of Medicine, Tokyo, Japan.
authors: Yoshiyasu
authors: Y
authors: Aizawa
authors: Department of Cardiology, Keio University School of Medicine, Tokyo, Japan.
authors: Keiichi
authors: K
authors: Fukuda
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D000818:Animals; D044466:Asian People; D004562:Electrocardiography; D005260:Female; D017353:Gene Deletion; D005787:Gene Frequency; D055106:Genome-Wide Association Study; D006329:Heart Conduction System / Q000502:physiology*; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D019831:Sodium-Calcium Exchanger / Q000235:genetics* / Q000378:metabolism
chemical_list: D019831:Sodium-Calcium Exchanger; C110374:sodium-calcium exchanger 1