Genetic locus on mouse chromosome 7 controls elevated heart rate

• Published in: Physiological genomics Vol. 44; no. 13; pp. 689 - 698
• Main Authors: Smolock, Elaine M, Ilyushkina, Irina A, Ghazalpour, Anatole, Gerloff, Janice, Murashev, Arkady N, Lusis, Aldons J, Korshunov, Vyacheslav A
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.07.2012
• Subjects: Animals; Chromosomes, Mammalian - genetics; Crosses, Genetic; Female; Genetic Loci; Genome; Genome-Wide Association Study; Genotype; Heart Rate - genetics; Linkage Disequilibrium; Male; Mice - genetics; Polymorphism, Single Nucleotide; Quantitative Trait Loci
• ISSN: 1094-8341; 1531-2267
• DOI: 10.1152/physiolgenomics.00041.2012

Elevated heart rate (HR) is a risk factor for cardiovascular diseases. The goal of the study was to map HR trait in mice using quantitative trait locus (QTL) analysis followed by genome-wide association (GWA) analysis. The first approach provides mapping power and the second increases genome resolution. QTL analyses were performed in a C3HeB×SJL backcross. HR and systolic blood pressure (SBP) were measured by the tail-cuff plethysmography. HR was ∼80 beats/min higher in SJL compared with C3HeB. There was a wide distribution of the HR (536-763 beats/min) in N2 mice. We discovered a highly significant QTL (logarithm of odds = 6.7, P < 0.001) on chromosome 7 (41 cM) for HR in the C3HeB×SJL backcross. In the Hybrid Mouse Diversity Panel (58 strains, n = 5-6/strain) we found that HR (beats/min) ranged from 546 ± 12 in C58/J to 717 ± 7 in MA/MyJ mice. SBP (mmHg) ranged from 99 ± 6 in strain I/LnJ to 151 ± 4 in strain BXA4/PgnJ. GWA analyses were done using the HMDP, which revealed a locus (64.2-65.1 Mb) on chromosome 7 that colocalized with the QTL for elevated HR found in the C3HeB×SJL backcross. The peak association was observed for 17 SNPs that are localized within three GABA(A) receptor genes. In summary, we used a combined genetic approach to fine map a novel elevated HR locus on mouse chromosome 7.