| Literature DB >> 27577874 |
Daniel S Evans1, Christy L Avery2, Mike A Nalls3, Guo Li4, John Barnard5, Erin N Smith6, Toshiko Tanaka7, Anne M Butler2, Sarah G Buxbaum8,9, Alvaro Alonso10, Dan E Arking11, Gerald S Berenson12, Joshua C Bis4, Steven Buyske13, Cara L Carty14, Wei Chen15, Mina K Chung16,17,18, Steven R Cummings19, Rajat Deo20, Charles B Eaton21, Ervin R Fox22, Susan R Heckbert4,23,24, Gerardo Heiss2, Lucia A Hindorff25, Wen-Chi Hsueh26, Aaron Isaacs27,28, Yalda Jamshidi29, Kathleen F Kerr30, Felix Liu31, Yongmei Liu32, Kurt K Lohman32, Jared W Magnani33, Joseph F Maher34, Reena Mehra35, Yan A Meng36, Solomon K Musani37, Christopher Newton-Cheh36,38, Kari E North2,39, Bruce M Psaty4,23,24,40, Susan Redline41, Jerome I Rotter42, Renate B Schnabel43, Nicholas J Schork44, Ralph V Shohet45, Andrew B Singleton3, Jonathan D Smith46, Elsayed Z Soliman47, Sathanur R Srinivasan15, Herman A Taylor34, David R Van Wagoner17, James G Wilson48, Taylor Young36, Zhu-Ming Zhang47, Alan B Zonderman49, Michele K Evans49, Luigi Ferrucci7, Sarah S Murray50, Gregory J Tranah19, Eric A Whitsel2,51, Alex P Reiner4,14, Nona Sotoodehnia52,53.
Abstract
The electrocardiographic QRS duration, a measure of ventricular depolarization and conduction, is associated with cardiovascular mortality. While single nucleotide polymorphisms (SNPs) associated with QRS duration have been identified at 22 loci in populations of European descent, the genetic architecture of QRS duration in non-European populations is largely unknown. We therefore performed a genome-wide association study (GWAS) meta-analysis of QRS duration in 13,031 African Americans from ten cohorts and a transethnic GWAS meta-analysis with additional results from populations of European descent. In the African American GWAS, a single genome-wide significant SNP association was identified (rs3922844, P = 4 × 10-14) in intron 16 of SCN5A, a voltage-gated cardiac sodium channel gene. The QRS-prolonging rs3922844 C allele was also associated with decreased SCN5A RNA expression in human atrial tissue (P = 1.1 × 10-4). High density genotyping revealed that the SCN5A association region in African Americans was confined to intron 16. Transethnic GWAS meta-analysis identified novel SNP associations on chromosome 18 in MYL12A (rs1662342, P = 4.9 × 10-8) and chromosome 1 near CD1E and SPTA1 (rs7547997, P = 7.9 × 10-9). The 22 QRS loci previously identified in populations of European descent were enriched for significant SNP associations with QRS duration in African Americans (P = 9.9 × 10-7), and index SNP associations in or near SCN5A, SCN10A, CDKN1A, NFIA, HAND1, TBX5 and SETBP1 replicated in African Americans. In summary, rs3922844 was associated with QRS duration and SCN5A expression, two novel QRS loci were identified using transethnic meta-analysis, and a significant proportion of QRS-SNP associations discovered in populations of European descent were transferable to African Americans when adequate power was achieved.Entities:
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Year: 2016 PMID： 27577874 PMCID： PMC5291202 DOI： 10.1093/hmg/ddw284
Source DB: PubMed Journal: Hum Mol Genet ISSN： 0964-6906 Impact factor: 6.150