Assessing the causal role of body mass index on cardiovascular health in young adults: Mendelian randomization and recall-by-genotype analyses.

Wade, Kaitlin H, Chiesa, Scott T, Hughes, Alun D ORCID: 0000-0001-5432-5271, Chaturvedi, Nish, Charakida, Marietta, Rapala, Alicja, Muthurangu, Vivek, Khan, Tauseef, Finer, Nicholas, Sattar, Naveed
et al (show 6 more authors) (2018) Assessing the causal role of body mass index on cardiovascular health in young adults: Mendelian randomization and recall-by-genotype analyses. Circulation, 138 (20). pp. 2187-2201.

Access the full-text of this item by clicking on the Open Access link.


Background:Body mass index (BMI) has been suggested to be causally related to cardiovascular health in mid-to-late life, but this has not been explored systematically at younger ages - nor with detailed cardiovascular phenotyping. Recall-by-Genotype (RbG) is an approach that enables the collection of precise phenotypic measures in smaller studies, whilst maintaining statistical power and ability for causal inference. Methods:In this study, we used a combination of conventional multivariable regression analysis, Mendelian randomization (MR) and sub-sample RbG methodologies to estimate the causal effect of BMI on gross-level and detailed cardiovascular health in healthy participants from the Avon Longitudinal Study of Parents and Children at age 17 (N=1420-3108 for different outcomes) and an independent sample from the same cohort (for RbG) study at age 21 (N=386-418). Results:In both MR and RbG analyses, results suggested that higher BMI causes higher blood pressure (BP) and left ventricular mass index (LVMI) in young adults (e.g., difference in LVMI per kg/m2 using MR: 1.07g/m2.7; 95% CI: 0.62, 1.52; P=3.87x10-06 and per 3.58kg/m2 using RbG: 1.65g/m2.7 95% CI: 0.83, 2.47; P=0.0001). Additionally, RbG results suggested a causal role of higher BMI on higher stroke volume (SV: difference per 3.58kg/m2: 1.49ml/m2.04; 95% CI: 0.62, 2.35; P=0.001) and cardiac output (CO: difference per 3.58kg/m2: 0.11l/min/m1.83; 95% CI: 0.03, 0.19; P=0.01) but no strong evidence for a causal role on systemic vascular resistance or total arterial compliance. Neither analysis supported a causal role of higher BMI on heart rate. Conclusions:Complementary MR and RbG causal methodologies, together with a range of sensitivity analyses, suggest that higher BMI is likely to cause worse cardiovascular health, specifically higher BP and LVMI, even in youth. Higher BMI also resulted in increased CO in the RbG study, which appeared to be solely driven by SV, as neither MR nor RbG analyses suggested a causal effect of BMI on heart rate. These consistent results support efforts to reduce BMI from a young age to prevent later adverse cardiovascular health and illustrate the potential for phenotypic resolution with maintained analytical power using RbG.

Item Type: Article
Uncontrolled Keywords: Heart, Humans, Body Mass Index, Longitudinal Studies, Life Style, Heart Rate, Vascular Resistance, Ventricular Function, Left, Genotype, Phenotype, Polymorphism, Single Nucleotide, Adolescent, Female, Male, Adiposity, Genome-Wide Association Study, Young Adult, Mendelian Randomization Analysis, Carotid Intima-Media Thickness, Pulse Wave Analysis
Depositing User: Symplectic Admin
Date Deposited: 06 Feb 2019 16:43
Last Modified: 19 Jan 2023 01:05
DOI: 10.1161/CIRCULATIONAHA.117.033278
Open Access URL:
Related URLs: