DESCRIPTION:

List of positional candidate genes after correcting for multiple testing and controlling the false discovery rate from genome wide association studies (GWAS) retrieved from the NHGRI-EBI Catalog of published genome-wide association studies (http://www.ebi.ac.uk/gwas/). The disease/trait examined in this study, as reported by the authors, was QRS duration. The EFO term QRS duration was annotated to this set after curation by NHGRI-EBI. Intergenic SNPS were mapped to both the upstream and downstream gene. P-value uploaded. This gene set was generated using gwas2gs v. 0.1.8 and the GWAS Catalog v. 1.0.1.

LABEL:

GWAS: QRS duration

SCORE TYPE:

P-Value

DATE ADDED:

2017-05-02

DATE UPDATED:

2020-05-06

SPECIES:

AUTHORS:

DS Evans, CL Avery, MA Nalls, G Li, J Barnard, EN Smith, T Tanaka, AM Butler, SG Buxbaum, A Alonso, DE Arking, GS Berenson, JC Bis, S Buyske, CL Carty, W Chen, MK Chung, SR Cummings, R Deo, CB Eaton, ER Fox, SR Heckbert, G Heiss, LA Hindorff, WC Hsueh, A Isaacs, Y Jamshidi, KF Kerr, F Liu, Y Liu, KK Lohman, JW Magnani, JF Maher, R Mehra, YA Meng, SK Musani, C Newton-Cheh, KE North, BM Psaty, S Redline, JI Rotter, RB Schnabel, NJ Schork, RV Shohet, AB Singleton, JD Smith, EZ Soliman, SR Srinivasan, HA Taylor, DR Van Wagoner, JG Wilson, T Young, ZM Zhang, AB Zonderman, MK Evans, L Ferrucci, SS Murray, GJ Tranah, EA Whitsel, AP Reiner, N Sotoodehnia

TITLE:

Fine-mapping, novel loci identification, and SNP association transferability in a genome-wide association study of QRS duration in African Americans.

JOURNAL:

Human molecular genetics Oct 2016, Vol 25, pp. 4350-4368

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. PUBMED: 27577874
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