title: Genetic locus on mouse chromosome 7 controls elevated heart rate.
abstract: 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.
authors.affiliation: Department of Medicine, Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USA.
authors.forename: Elaine M
authors.initials: EM
authors.lastname: Smolock
authors.forename: Irina A
authors.initials: IA
authors.lastname: Ilyushkina
authors.forename: Anatole
authors.initials: A
authors.lastname: Ghazalpour
authors.forename: Janice
authors.initials: J
authors.lastname: Gerloff
authors.forename: Arkady N
authors.initials: AN
authors.lastname: Murashev
authors.forename: Aldons J
authors.initials: AJ
authors.lastname: Lusis
authors.forename: Vyacheslav A
authors.initials: VA
authors.lastname: Korshunov
mesh_terms: D000818:Animals; D033481:Chromosomes, Mammalian / Q000235:genetics*; D003433:Crosses, Genetic; D005260:Female; D056426:Genetic Loci; D016678:Genome; D055106:Genome-Wide Association Study; D005838:Genotype; D006339:Heart Rate / Q000235:genetics*; D015810:Linkage Disequilibrium; D008297:Male; D051379:Mice / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci