Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

Low LDL cholesterol, PCSK9 and HMGCR genetic variation, and risk of Alzheimer's disease and Parkinson's disease: Mendelian randomisation study

Research output: Contribution to journalJournal articleResearchpeer-review

  1. SARS-CoV-2 vaccination and myocarditis or myopericarditis: population based cohort study

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. Coagulation parameters in the newborn and infant - the Copenhagen Baby Heart and COMPARE studies

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Lipoprotein(a) levels at birth and in early childhood: The COMPARE Study

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Triglyceride-rich Lipoprotein Cholesterol (Remnant Cholesterol) as a Therapeutic Target for Cardiovascular Disease Risk

    Research output: Chapter in Book/Report/Conference proceedingBook chapterCommunication

  4. A possible explanation for the contrasting results of REDUCE-IT vs. STRENGTH: cohort study mimicking trial designs

    Research output: Contribution to journalJournal articleResearchpeer-review

View graph of relations

Objective To test the hypothesis that low density lipoprotein (LDL) cholesterol due to genetic variation in the genes responsible for LDL cholesterol metabolism and biosynthesis(PCSK9 and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), respectively) is associated with a high risk of Alzheimer's disease, vascular dementia, any dementia, and Parkinson's disease in the general population.Design Mendelian randomisation study.Setting Copenhagen General Population Study and Copenhagen City Heart Study.Participants 111 194 individuals from the Danish general population.Main outcome measures Risk of Alzheimer's disease, vascular dementia, all dementia, and Parkinson's disease.Results In observational analyses, the multifactorially adjusted hazard ratio for Parkinson's disease in participants with an LDL cholesterol level <1.8 mmol/L versus ≥4.0 mmol/L was 1.70 (95% confidence interval 1.03 to 2.79), whereas the corresponding hazard ratios for Alzheimer's disease, vascular dementia, or any dementia did not differ from 1.0. PCSK9 and HMGCR variants combined were associated with a 9.3% lower LDL cholesterol level. In genetic, causal analyses adjusted for age, sex, and year of birth, the risk ratios for a lifelong 1 mmol/L lower LDL cholesterol level were 0.57 (0.27 to 1.17) for Alzheimer's disease, 0.81 (0.34 to 1.89) for vascular dementia, 0.66 (0.34 to 1.26) for any dementia, and 1.02 (0.26 to 4.00) for Parkinson's disease. Summary level data from the International Genomics of Alzheimer's Project using Egger Mendelian randomisation analysis gave a risk ratio for Alzheimer's disease of 0.24 (0.02 to 2.79) for 26 PCSK9 and HMGCR variants, and of 0.64 (0.52 to 0.79) for 380 variants of LDL cholesterol level lowering.Conclusion Low LDL cholesterol levels due to PCSK9 and HMGCR variants had no causal effect on high risk of Alzheimer's disease, vascular dementia, any dementia, or Parkinson's disease; however, low LDL cholesterol levels may have a causal effect in reducing the risk of Alzheimer's disease.

Original languageEnglish
JournalBMJ
Volume357
Pages (from-to)j1648
ISSN1756-1833
Publication statusPublished - 24 Apr 2017

    Research areas

  • Adult, Aged, Alzheimer Disease, Biomarkers, Cholesterol, LDL, Denmark, Female, Follow-Up Studies, Genetic Predisposition to Disease, Genetic Variation, Genotype, Humans, Hydroxymethylglutaryl CoA Reductases, Male, Mendelian Randomization Analysis, Middle Aged, Parkinson Disease, Proportional Hazards Models, Proprotein Convertase 9, Prospective Studies, Journal Article, Observational Study

ID: 52188781