Cristina Menni1, Massimo Mangino, Feng Zhang, Gail Clement, Harold Snieder, Sandosh Padmanabhan, Tim D Spector. 1. aDepartment of Twin Research & Genetic Epidemiology, King's College London, London, UK bDepartment of Epidemiology, University of Groningen, University Medical Center Groningen, The Netherlands cBritish Heart Foundation (BHF) Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK.
Abstract
BACKGROUND: Clinic and long-term average blood pressure (BP) are heritable traits with estimates of heritability ranging from 0.31 to 0.68. Long-term visit-to-visit BP variability (BPV) is emerging as a new cardiovascular risk predictor, though it is unclear if this is completely independent of BP. We hypothesize that BPV should demonstrate the same pattern of additive genetic, shared environmental and unique environmental variance as BP, if both are phenotypic surrogates. METHOD: We studied 2889 twin pairs not on any BP-lowering therapy from the Twins UK cohort, and estimated the additive genetic variance for baseline BP, long-term average BP, BP trajectory (rate of change of BP in mmHg/year) and BPV (coefficient of variation and average real variability over an average of 3.2 visits). Heritability estimates were obtained by structural equation modelling adjusting for age, age, sex and BMI. RESULTS: The heritabilities for baseline SBP and DBP were 0.51 (95% confidence interval 0.49, 0.53) and 0.56 (0.54, 0.58); long-term average SBP and DBP were 0.56 (0.53, 0.59) and 0.61 (0.58, 0.64); and systolic and diastolic trajectories over 10 years were 0.49 (0.46, 0.52) and 0.29 (0.27, 0.32), respectively. Both overall systolic and diastolic BPV showed no additive genetic variance contributing to the phenotypic variation, but after stratification by age, the younger subgroup (<51 years) showed heritability estimates of 0.44 (0.38, 0.50) for coefficient of variation and 0.35 (0.29, 0.41) for average real variability. CONCLUSION: Age is a major factor that influences heritability estimation of BPV and it is likely that BPV in younger and older age groups may reflect different pathological phenotypes.
BACKGROUND: Clinic and long-term average blood pressure (BP) are heritable traits with estimates of heritability ranging from 0.31 to 0.68. Long-term visit-to-visit BP variability (BPV) is emerging as a new cardiovascular risk predictor, though it is unclear if this is completely independent of BP. We hypothesize that BPV should demonstrate the same pattern of additive genetic, shared environmental and unique environmental variance as BP, if both are phenotypic surrogates. METHOD: We studied 2889 twin pairs not on any BP-lowering therapy from the Twins UK cohort, and estimated the additive genetic variance for baseline BP, long-term average BP, BP trajectory (rate of change of BP in mmHg/year) and BPV (coefficient of variation and average real variability over an average of 3.2 visits). Heritability estimates were obtained by structural equation modelling adjusting for age, age, sex and BMI. RESULTS: The heritabilities for baseline SBP and DBP were 0.51 (95% confidence interval 0.49, 0.53) and 0.56 (0.54, 0.58); long-term average SBP and DBP were 0.56 (0.53, 0.59) and 0.61 (0.58, 0.64); and systolic and diastolic trajectories over 10 years were 0.49 (0.46, 0.52) and 0.29 (0.27, 0.32), respectively. Both overall systolic and diastolic BPV showed no additive genetic variance contributing to the phenotypic variation, but after stratification by age, the younger subgroup (<51 years) showed heritability estimates of 0.44 (0.38, 0.50) for coefficient of variation and 0.35 (0.29, 0.41) for average real variability. CONCLUSION: Age is a major factor that influences heritability estimation of BPV and it is likely that BPV in younger and older age groups may reflect different pathological phenotypes.
Authors: Julia K Goodrich; Emily R Davenport; Michelle Beaumont; Matthew A Jackson; Rob Knight; Carole Ober; Tim D Spector; Jordana T Bell; Andrew G Clark; Ruth E Ley Journal: Cell Host Microbe Date: 2016-05-11 Impact factor: 21.023