APOE and Alzheimer disease: Although polygenic Mendelian randomization analyses excluding variants from the APOE gene region have consistently given null results,78 a previous cis-Mendelian randomization analysis for LDL cholesterol and Alzheimer disease based solely on variants in the PCSK9 gene region gave an inverse estimate of OR 0.69 (95% CI: 0.59, 0.81) per standard deviation increase in genetically predicted LDL cholesterol, suggesting that lowering LDL cholesterol via PCSK9 inhibition may increase risk of Alzheimer disease.79