Genome-Wide Linkage Analysis of Hemodynamic Parameters Under Mental and Physical Stress in Extended Omani Arab Pedigrees: The Oman Family Study

Abstract

Background:We performed a genome-wide scan in a homogeneous Arab population to identify genomic regions linked to blood pressure (BP) and its intermediate phenotypes during mental and physical stress tests.Methods:The Oman Family Study subjects (N= 1277) were recruited from five extended families of ~10 generations. Hemodynamic phenotypes were computed from beat-to-beat BP, electrocardiography and impedance cardiography. Multi-point linkage was performed for resting, mental (word conflict test, WCT) and cold pressor (CPT) stress and their reactivity scores (s), using variance components decomposition-based methods implemented in SOLAR.Results:Genome-wide scans for BP phenotypes identified quantitative trait loci (QTLs) with significant evidence of linkage on chromosomes 1 and 12 for WCT-linked cardiac output (LOD = 3.1) and systolic BP (LOD = 3.5). Evidence for suggestive linkage for WCT was found on chromosomes 3, 17 and 1 for heart rate (LOD = 2.3), DBP (LOD = 2.4) and left ventricular ejection time (LVET), respectively. For △WCT, suggestive QTLs were detected for CO on chr11 (LOD = 2.5), LVET on chr3 (LOD = 2.0) and EDI on chr9 (LOD = 2.1). For CPT, suggestive QTLs for HR and LVET shared the same region on chr22 (LOD 2.3 and 2.8, respectively) and on chr9 (LOD = 2.3) for SBP, chr7 (LOD = 2.4) for SV and chr19 (LOD = 2.6) for CO. For △CPT, CO and TPR top signals were detected on chr15 and 10 (LOD; 2.40, 2.08) respectively. Conclusion: Mental stress revealed the largest number of significant and suggestive loci for normal BP reported to date. The study of BP and its intermediate phenotypes under mental and physical stress may help reveal the genes involved in the pathogenesis of essential hypertension.

Heritability and genetic correlations of heart rate variability at rest and during stress in the Oman Family Study

“…Each family is currently living in separate villages. The geographical particularity of this area is that it is relatively isolated with a topography of mountains, oases, and seasonal river beds, which provides a more homogenous environmental exposure [ 25 , 26 ]. Furthermore, more than 50% of all marriages are first-cousin marriages with polygamy being widely practiced with some men marrying up to four wives.…”

“…Participants were monitored throughout to ensure that arrhythmias did not arise at rest or during interventions. Throughout the study, tests and measurements were administered by a research assistant of the same sex as the study participant [ 25 , 26 ]. See Supplementary for details.…”

“…Beat-to-beat HR was obtained from lead II of the ECG [ 25 , 26 , 28 ] with sampling frequency of 1000 Hz. The algorithm used by the Task Force Monitor corrected for artefacts such as ventricular ectopy [ 29 ].…”

Genome-Wide Linkage and Regional Association Study of Blood Pressure Response to the Cold Pressor Test in Han Chinese

“…Only one other linkage scan was conducted previously in an Arabic population but did not identify any suggestive linkage signals. 15 While prior linkage scans have not linked this region at 20p13 - 20p12.3 to the correlated BP or hypertension phenotypes, this region was linked to asthma, 39 a trait that has been tied previously to both autonomic-cardiovascular control 40 and BP response to CPT. 41 Although further research in this area is needed, these findings suggest a potentially shared genetic basis for cardiovascular and respiratory autonomic functions.…”

“…11–14 While some studies have been conducted to identify the genetic mechanisms underlying this complex phenotype, 15–25 most of the genomic research has been hypothesis driven 16–24 and carried out among participants of European ancestry. 15–21 The aim of the current study was to identify chromosomal regions harboring novel quantitative trait loci (QTLs) for systolic BP (SBP), diastolic BP (DBP), and mean arterial pressure (MAP) responses to CPT by conducting a genome-wide linkage scan among Han Chinese participants of the Genetic Epidemiology Network of Salt Sensitivity (GenSalt) study. To localize signals identified by the genome-wide scans, we genotyped a dense panel of SNPs located in promising linkage regions and conducted both single-marker and gene-based association analyses of the BP response phenotypes.…”