trailGenetic instruments for LDL cholesterol affect cardiovascular risk only through LDL and not through confounding pleiotropy
Mendelian randomization studies show genetically lower LDL cholesterol causally reduces cardiovascular disease risk
Robustness to pleiotropy· for
MR sensitivity analyses find no evidence of directional pleiotropy in the genetic LDL–cardiovascular disease relationship
LDL–cardiovascular causal estimates are concordant across pleiotropy-robust MR methods
Genetic instruments in distinct LDL-related genes yield concordant estimates of LDL's effect on cardiovascular risk
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Multivariable Mendelian randomization adjusting for HDL and triglycerides shows LDL retains an independent causal effect on cardiovascular risk
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Pleiotropy of lipid variants· against
Genetic variants that lower LDL cholesterol frequently also affect other lipid traits such as triglycerides and HDL
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Genetic instruments for LDL cholesterol affect cardiovascular risk only through LDL and not through confounding pleiotropy
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