| Title | Common and Rare Coding Genetic Variation Underlying the Electrocardiographic PR Interval. |
| Publication Type | Journal Article |
| Year of Publication | 2018 |
| Authors | Lin H, van Setten J, Smith AV, Bihlmeyer NA, Warren HR, Brody JA, Radmanesh F, Hall L, Grarup N, Müller-Nurasyid M, Boutin T, Verweij N, Lin HJ, Li-Gao R, van den Berg ME, Marten J, Weiss S, Prins BP, Haessler J, Lyytikäinen L-P, Mei H, Harris TB, Launer LJ, Li M, Alonso A, Soliman EZ, Connell JM, Huang PL, Weng L-C, Jameson HS, Hucker W, Hanley A, Tucker NR, Chen Y-D I, Bis JC, Rice KM, Sitlani CM, Kors JA, Xie Z, Wen C, Magnani JW, Nelson CP, Kanters JK, Sinner MF, Strauch K, Peters A, Waldenberger M, Meitinger T, Bork-Jensen J, Pedersen O, Linneberg A, Rudan I, de Boer RA, van der Meer P, Yao J, Guo X, Taylor KD, Sotoodehnia N, Rotter JI, Mook-Kanamori DO, Trompet S, Rivadeneira F, Uitterlinden A, Eijgelsheim M, Padmanabhan S, Smith BH, Völzke H, Felix SB, Homuth G, Völker U, Mangino M, Spector TD, Bots ML, Perez M, Kähönen M, Raitakari OT, Gudnason V, Arking DE, Munroe PB, Psaty BM, van Duijn CM, Benjamin EJ, Rosand J, Samani NJ, Hansen T, Kääb S, Polasek O, van der Harst P, Heckbert SR, J Jukema W, Stricker BH, Hayward C, Dörr M, Jamshidi Y, Asselbergs FW, Kooperberg C, Lehtimäki T, Wilson JG, Ellinor PT, Lubitz SA |
| Secondary Authors | Isaacs A |
| Journal | Circ Genom Precis Med |
| Volume | 11 |
| Issue | 5 |
| Pagination | e002037 |
| Date Published | 2018 05 |
| ISSN | 2574-8300 |
| Keywords | Adult, Aged, Electrocardiography, Female, Genetic Variation, Genome-Wide Association Study, Humans, Male, Middle Aged, Quantitative Trait Loci, Regulatory Sequences, Nucleic Acid |
| Abstract | BACKGROUND: Electrical conduction from the cardiac sinoatrial node to the ventricles is critical for normal heart function. Genome-wide association studies have identified more than a dozen common genetic loci that are associated with PR interval. However, it is unclear whether rare and low-frequency variants also contribute to PR interval heritability. METHODS: We performed large-scale meta-analyses of the PR interval that included 83 367 participants of European ancestry and 9436 of African ancestry. We examined both common and rare variants associated with the PR interval. RESULTS: We identified 31 genetic loci that were significantly associated with PR interval after Bonferroni correction ( CONCLUSIONS: We identified common variants at 11 novel loci and rare variants within 2 gene regions that were significantly associated with PR interval. Our findings provide novel insights to the current understanding of atrioventricular conduction, which is critical for cardiac activity and an important determinant of health. |
| DOI | 10.1161/CIRCGEN.117.002037 |
| Alternate Journal | Circ Genom Precis Med |
| PubMed ID | 29748316 |
| PubMed Central ID | PMC5951629 |
| Grant List | R01 HL139731 / HL / NHLBI NIH HHS / United States K24 HL105780 / HL / NHLBI NIH HHS / United States R01 HL092577 / HL / NHLBI NIH HHS / United States U01 HL130114 / HL / NHLBI NIH HHS / United States R01 HL128914 / HL / NHLBI NIH HHS / United States R01 HL105756 / HL / NHLBI NIH HHS / United States T32 HL007208 / HL / NHLBI NIH HHS / United States P30 DK063491 / DK / NIDDK NIH HHS / United States S10 OD020069 / OD / NIH HHS / United States UL1 TR001881 / TR / NCATS NIH HHS / United States U54 GM115428 / GM / NIGMS NIH HHS / United States K23 HL114724 / HL / NHLBI NIH HHS / United States R01 HL111089 / HL / NHLBI NIH HHS / United States R01 HL116747 / HL / NHLBI NIH HHS / United States UL1 TR001430 / TR / NCATS NIH HHS / United States |