You are here

Fifteen Genetic Loci Associated With the Electrocardiographic P Wave.

TitleFifteen Genetic Loci Associated With the Electrocardiographic P Wave.
Publication TypeJournal Article
Year of Publication2017
AuthorsChristophersen, IE, Magnani, JW, Yin, X, Barnard, J, Weng, L-C, Arking, DE, Niemeijer, MN, Lubitz, SA, Avery, CL, Duan, Q, Felix, SB, Bis, JC, Kerr, KF, Isaacs, A, Müller-Nurasyid, M, Müller, C, North, KE, Reiner, AP, Tinker, LF, Kors, JA, Teumer, A, Petersmann, A, Sinner, MF, Bůzková, P, Smith, JD, Van Wagoner, DR, Völker, U, Waldenberger, M, Peters, A, Meitinger, T, Limacher, MC, Wilhelmsen, KC, Psaty, BM, Hofman, A, Uitterlinden, A, Krijthe, BP, Zhang, Z-M, Schnabel, RB, Kääb, S, van Duijn, C, Rotter, JI, Sotoodehnia, N, Dörr, M, Li, Y, Chung, MK, Soliman, EZ, Alonso, A, Whitsel, EA, Stricker, BH, Benjamin, EJ, Heckbert, SR, Ellinor, PT
JournalCirc Cardiovasc Genet
Date Published2017 Aug
KeywordsArrhythmias, Cardiac, Caveolin 1, Caveolin 2, Electrocardiography, Genetic Loci, Genome-Wide Association Study, Genotype, Heart Atria, Humans, NAV1.5 Voltage-Gated Sodium Channel, NAV1.8 Voltage-Gated Sodium Channel, T-Box Domain Proteins
Abstract<p><b>BACKGROUND: </b>The P wave on an ECG is a measure of atrial electric function, and its characteristics may serve as predictors for atrial arrhythmias. Increased mean P-wave duration and P-wave terminal force traditionally have been used as markers for left atrial enlargement, and both have been associated with increased risk of atrial fibrillation. Here, we explore the genetic basis of P-wave morphology through meta-analysis of genome-wide association study results for P-wave duration and P-wave terminal force from 12 cohort studies.</p><p><b>METHODS AND RESULTS: </b>We included 44 456 individuals, of which 6778 (16%) were of African ancestry. Genotyping, imputation, and genome-wide association study were performed at each study site. Summary-level results were meta-analyzed centrally using inverse-variance weighting. In meta-analyses of P-wave duration, we identified 6 significant (P<5×10-8) novel loci and replicated a prior association with SCN10A. We identified 3 loci at SCN5A, TBX5, and CAV1/CAV2 that were jointly associated with the PR interval, PR segment, and P-wave duration. We identified 6 novel loci in meta-analysis of P-wave terminal force. Four of the identified genetic loci were significantly associated with gene expression in 329 left atrial samples. Finally, we observed that some of the loci associated with the P wave were linked to overall atrial conduction, whereas others identified distinct phases of atrial conduction.</p><p><b>CONCLUSIONS: </b>We have identified 6 novel genetic loci associated with P-wave duration and 6 novel loci associated with P-wave terminal force. Future studies of these loci may aid in identifying new targets for drugs that may modify atrial conduction or treat atrial arrhythmias.</p>
Alternate JournalCirc Cardiovasc Genet
PubMed ID28794112
PubMed Central IDPMC5567993
Grant ListK24 HL105780 / HL / NHLBI NIH HHS / United States
R01 HL092577 / HL / NHLBI NIH HHS / United States
U01 HL130114 / HL / NHLBI NIH HHS / United States
UL1 TR000124 / TR / NCATS NIH HHS / United States
R01 HL128914 / HL / NHLBI NIH HHS / United States
R01 HL105756 / HL / NHLBI NIH HHS / United States
P30 DK063491 / DK / NIDDK NIH HHS / United States
R01 HL111314 / HL / NHLBI NIH HHS / United States
UL1 TR001881 / TR / NCATS NIH HHS / United States
ePub date: