swvanderlaan / 2016_jacc_27561768_vanderlaan_sw_cystatinc

Cystatin C and Cardiovascular Disease: A Mendelian Randomization Study.

Cystatin C and Cardiovascular Disease: A Mendelian Randomization Study

This readme

This readme accompanies the paper "Cystatin C and Cardiovascular Disease: A Mendelian Randomization Study." by Van der Laan S.W. et al. JACC 2016.

Abstract

Background Epidemiological studies show that high circulating cystatin C is associated with risk of cardiovascular disease (CVD), independent of creatinine-based renal function measurements. It is unclear whether this relationship is causal, arises from residual confounding, and/or is a consequence of reverse causation.

Objectives The aim of this study was to use Mendelian randomization to investigate whether cystatin C is causally related to CVD in the general population.

Methods We incorporated participant data from 16 prospective cohorts (n = 76,481) with 37,126 measures of cystatin C and added genetic data from 43 studies (n = 252,216) with 63,292 CVD events. We used the common variant rs911119 in CST3 as an instrumental variable to investigate the causal role of cystatin C in CVD, including coronary heart disease, ischemic stroke, and heart failure.

Results Cystatin C concentrations were associated with CVD risk after adjusting for age, sex, and traditional risk factors (relative risk: 1.82 per doubling of cystatin C; 95% confidence interval [CI]: 1.56 to 2.13; p = 2.12 × 10−14). The minor allele of rs911119 was associated with decreased serum cystatin C (6.13% per allele; 95% CI: 5.75 to 6.50; p = 5.95 × 10−211), explaining 2.8% of the observed variation in cystatin C. Mendelian randomization analysis did not provide evidence for a causal role of cystatin C, with a causal relative risk for CVD of 1.00 per doubling cystatin C (95% CI: 0.82 to 1.22; p = 0.994), which was statistically different from the observational estimate (p = 1.6 × 10−5). A causal effect of cystatin C was not detected for any individual component of CVD.

Conclusions Mendelian randomization analyses did not support a causal role of cystatin C in the etiology of CVD. As such, therapeutics targeted at lowering circulating cystatin C are unlikely to be effective in preventing CVD.

Here you can find the R-script used to calculate power, MR_Power_Binary.R, which generates the graph below.

Notes

Scripts will work within the context of a certain Linux environment, for example a CentOS7 system on a SUN Grid Engine background or macOS X Lion+ (version 10.7.[x]+).

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Copyright (c) 1979-present Sander W. van der Laan | s.w.vanderlaan [at] gmail [dot] com.

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