2010
DOI: 10.1038/ng.517
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Genome-wide association study of PR interval

Abstract: The electrocardiographic PR interval reflects atrial and atrioventricular nodal conduction, disturbances of which increase risk of atrial fibrillation (AF). To identify underlying common genetic variation, we meta-analyzed genome-wide association results for PR interval from seven community-based studies of European-ancestry individuals in the CHARGE consortium: AGES, ARIC, CHS, FHS, KORA, Rotterdam Study, and SardiNIA (N=28,517). Statistically significant loci (P<5×10-8) were tested for association with AF (N… Show more

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Cited by 400 publications
(457 citation statements)
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References 51 publications
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“…18 Knock-out mouse models have revealed that PRRX1 is necessary for the normal development of great vessels and lung vascularization. 34,35 The SNP rs1152591 is located on chromosome 14q23, in an intron of the gene SYNE2 encoding nesprin 2, which is a linker of nucleoskeleton and cytoskeleton (LINC) protein involved in maintaining cellular architecture and nuclear integrity. 36 It is highly expressed in heart and skeletal muscle, and mutations in SYNE2 have been identified in families with Emery-Dreifuss muscular dystrophy.…”
Section: The 4q25 Locusmentioning
confidence: 99%
“…18 Knock-out mouse models have revealed that PRRX1 is necessary for the normal development of great vessels and lung vascularization. 34,35 The SNP rs1152591 is located on chromosome 14q23, in an intron of the gene SYNE2 encoding nesprin 2, which is a linker of nucleoskeleton and cytoskeleton (LINC) protein involved in maintaining cellular architecture and nuclear integrity. 36 It is highly expressed in heart and skeletal muscle, and mutations in SYNE2 have been identified in families with Emery-Dreifuss muscular dystrophy.…”
Section: The 4q25 Locusmentioning
confidence: 99%
“…The loci at SCN10A and SCN5A are also associated with both PR interval and QRS duration. 32,33 From an evolutionary perspective, our results may suggest that these common variants known to increase the risk of a rare, but potentially lethal syndrome such as BrS seem to have a dualistic effect, protecting against a much more common disease such as AF.…”
Section: Discussionmentioning
confidence: 90%
“…39 An altered SCN5A/SCN10A expression could affect the conduction velocity and thereby the risk for BrS. Of note, both the SCN5A SNP rs11708996 and the SCN10A SNP rs10428132 have previously been associated with PR interval duration in a GWAS, 32 supporting a protective role in AF. Pazoki et al 40 replicated the association between the SCN5A SNP and PR duration, showing a trend for association between the rs11708996 C allele and a PR interval of Z200 ms (OR ¼ 2.39, P ¼ 0.004).…”
Section: Discussionmentioning
confidence: 95%
“…It scores each item on a scale from 0 (no deficit) to 4 (absence of function=severe deficit), for a total range score from 0 to 28. 14 According to the TNSc, the severity of cumulative OXAIPN was classified for the purposes of the current study as grade 1 (scores of 1-7), grade 2 (scores of [8][9][10][11][12][13][14], grade 3 (scores of [15][16][17][18][19][20][21], and grade 4 (scores > 21).…”
Section: Outcome Measuresmentioning
confidence: 99%
“…Both SCN10A SNPs (ie, rs12632942 [changes residue at position 1092 from leucine to proline] and rs6800541 [an intronic SNP C=T]) were chosen because they may be associated with the partial response interval as shown in previous studies, suggesting an important role regarding the final protein product. 18 With regard to SCN4A, the intronic SNP rs2302237 was chosen after searching the SNP database at the National Center for Biotechnology Information for SNPs with a known frequency in the European population and a minor allele frequency > 0.1. Finally, SCN9A-rs6746030 was chosen due to its association with an altered pain threshold.…”
Section: Genotypingmentioning
confidence: 99%