Abstract
Background: We investigated causal effect of completed growth, measured by adult height, on coronary heart disease (CHD), stroke and cardiovascular traits, using instrumental variable (IV) Mendelian randomization meta-analysis. Methods: We developed an allele score based on 69 single nucleotide polymorphisms (SNPs) associated with adult height, identified by the IBCCardioChip, and used it for IV analysis against cardiovascular risk factors and events in 21 studies and 60 028 participants. IV analysis on CHD was supplemented by summary data from 180 height-SNPs from the GIANT consortium and their corresponding CHD estimates derived from CARDIoGRAMplusC4D. Results: IV estimates from IBCCardioChip and GIANT-CARDIoGRAMplusC4D showed that a 6.5-cm increase in height reduced the odds of CHD by 10% [odds ratios 0.90; 95% confidence intervals (CIs): 0.78 to 1.03 and 0.85 to 0.95, respectively],which agrees with the estimate from the Emerging Risk Factors Collaboration (hazard ratio 0.93; 95% CI: 0.91 to 0.94). IV analysis revealed no association with stroke (odds ratio 0.97; 95% CI: 0.79 to 1.19). IV analysis showed that a 6.5-cm increase in height resulted in lower levels of body mass index (P < 0.001), triglycerides (P < 0.001), non high-density (non-HDL) cholesterol (P < 0.001), C-reactive protein (P = 0.042), and systolic blood pressure (P = 0.064) and higher levels of forced expiratory volume in 1 s and forced vital capacity (P < 0.001 for both). Conclusions: Taller individuals have a lower risk of CHD with potential explanations being that taller people have a better lung function and lower levels of body mass index, cholesterol and blood pressure.
Highlights
Observational studies have shown associations of adult height used as a measure of completed growth, with major non-communicable diseases.[1,2,3,4] Studying over 1 million participants, the Emerging Risk Factors Collaboration (ERFC) found a 6% decrease in risk of dying from coronary heart disease (CHD) and stroke per 6.5 cm increase in adult height.[4]
The second was based on summary data from 180 statistically independent height-associated single nucleotide polymorphisms (SNPs) from the Genetic Investigation of ANthropometric Traits (GIANT) Consortium[12] and their corresponding summary CHD estimates derived from the Coronary Artery Disease Genomewide Replication and Meta-analysis (CARDIoGRAM) plus the Coronary Artery Disease (C4D) Genetics Consorium, collectively known as CARDIoGRAMplusC4D,13 downloaded from [http://www.CARDIOGRAMPLUSC4D.org]
Adult height increased by 0.79 cm per one-unit increase in allele score derived from the IBC CardioChip array with low heterogeneity across studies (I2 1⁄4 29%, P 1⁄4 0.108) (Figure 1), and explained
Summary
Observational studies have shown associations of adult height used as a measure of completed growth, with major non-communicable diseases.[1,2,3,4] Studying over 1 million participants, the Emerging Risk Factors Collaboration (ERFC) found a 6% decrease in risk of dying from coronary heart disease (CHD) and stroke per 6.5 cm increase in adult height.[4]. Given that genetic variants are unlikely to be affected by the wide range of confounders that usually bias multivariable analyses and cannot be influenced by reverse causality, we employed a multiple instruments Mendelian randomization approach[7,8,9] to investigate the causal effect of completed growth, measured by adult height, with CHD and stroke and examine several cardiovascular traits to gain insight about potential mechanisms. We investigated causal effect of completed growth, measured by adult height, on coronary heart disease (CHD), stroke and cardiovascular traits, using instrumental variable (IV) Mendelian randomization meta-analysis. Results: IV estimates from IBCCardioChip and GIANT-CARDIoGRAMplusC4D showed that a 6.5-cm increase in height reduced the odds of CHD by 10% [odds ratios 0.90; 95% confidence intervals (CIs): 0.78 to 1.03 and 0.85 to 0.95, respectively],which agrees with the estimate from the Emerging Risk Factors Collaboration (hazard ratio 0.93; 95% CI: 0.91 to 0.94). Conclusions: Taller individuals have a lower risk of CHD with potential explanations being that taller people have a better lung function and lower levels of body mass index, cholesterol and blood pressure
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