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Heritability analyses show visit-to-visit blood pressure variability reflects different pathological phenotypes in younger and older adults: evidence from UK twins

Menni, Cristinaa; Mangino, Massimoa; Zhang, Fenga; Clement, Gaila; Snieder, Haroldb; Padmanabhan, Sandoshc; Spector, Tim D.a

doi: 10.1097/HJH.0b013e32836523c1
ORIGINAL PAPERS: Genetic aspects

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, age2, 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.

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

Correspondence to Dr Sandosh Padmanabhan, BHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow G12 8TA, UK. E-mail: sandosh.padmanabhan@glasgow.ac.uk

Abbreviations: A, additive genetic variance; AIC, Akaike information criterion; AVR, average real variability; BP, blood pressure; BPV, blood pressure variability; C, shared/common environmental variance; CKD, chronic kidney disease; E, unique environmental variance; h2, heritability

Received 4 December, 2012

Revised 21 May, 2013

Accepted 16 July, 2013

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© 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins