Heritability and Whole Genome Linkage of Pulse Pressure in Chinese Twin Pairs

Abstract

Elevated pulse pressure is associated with cardiovascular disorders and mortality in various populations. The genetic influence on pulse pressure has been confirmed by heritability estimates using related individuals. Recently, efforts have been made in mapping genes that are linked to the phenotype. We report results on our heritability and linkage study conducted on the Chinese population in mainland China where cardiovascular and cerebrovascular diseases are becoming the leading cause of death. A total of 630 pairs of middle-aged Chinese twins were collected for heritability analysis, from which 63 dizygotic twin pairs were randomly selected for genome-wide linkage analysis using Affymetrix 6.0 SNP array. Regression analysis reconfirmed the significant effects of age, sex, and BMI on pulse pressure. Comparison of twin models suggested the parsimonious AE model as the best model with a heritability estimate of 0.45. Genome-wide non-parametric linkage analysis identified three significant linkage peaks on chromosome 11 (lod score 4.06 at 30.5 cM), chromosome 12 (lod score 3.97 at 100.7 cM), and chromosome 18 (lod score 4.01 at 70.7 cM) with the last two peaks closely overlapping with linkage peaks reported by two American studies. In addition, multiple regions with suggestive linkage were identified with many of them overlapping with published linkage regions. Our results provide both epidemiological and molecular genetic evidence for the genetic dissection of pulse pressure in the Chinese population, which could help in fine mapping and in characterizing genes that are involved in the regulation of pulse pressure.

A Novel SNP Associated with Nighttime Pulse Pressure in Young-Onset Hypertension Patients Could Be a Genetic Prognostic Factor for Cardiovascular Events in a General Cohort in Taiwan

“…Further studies will be required to clarify functional relation between FLJ12164 and TGFA responsible for blood pressure regulation. Interestingly, a recent linkage study investigating heritability of PP among Chinese twin pairs found3 linkage peaks on chromosomes 11, 12 and 18 [33] , which are different from ours. However, instead of ambulatory BP monitoring, that study was based on a single-point BP value.…”

Past, present and future of cardiovascular twin studies

“…An English twin study certified similar heritability of PP compared to our findings (43%) [25]. A Chinese twin study provided both epidemiological and molecular genetic evidence for the genetic dissection of pulse pressure, which could help in fine mapping and in characterizing genes that are involved in the regulation of PP [26]. A recent Chinese twin study assessed eight metabolic factors (body mass index, waist circumference, waist-to-hip ratio, total serum cholesterol, serum triglycerides, serum uric acid besides systolic and diastolic blood pressure) in 508 twin pairs aged 8-17 years and reported that the effect of genetic factors on most metabolic traits decreased from childhood to adolescence [27].…”

Genetic Contribution to the Variance of Blood Pressure and Heart Rate: A Systematic Review and Meta-Regression of Twin Studies

“…A total of 23 heritability estimates in SBP, 22 estimates in DBP, 7 in HR and 4 in PP were identified from 17 twin studies since year 2001 (Baird et al, 2001; Dalageorgou et al, 2008; De Geus et al, 2007; Evans et al, 2003; Fagard et al, 2003; Jermendy et al, 2011; Jiang et al, 2012; Kennedy et al, 2005; Li et al, 2013; Mutikainen et al, 2009; Peeters et al, 2008; Snieder et al, 2003; Tarnoki et al, 2012; Vinck et al, 2001; Wu et al, 2011; Zeegers et al, 2004; Zhang et al, 2009). There were four estimates in SBP, four in DBP, and two in HR reported by sex specifically; five estimates in SBP, five in DBP, and two estimates in HR reported by age subgroup separately.…”