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Inherited High HDL Cholesterol, Blood Pressure May Play Role in AD Pathogenesis
Genetically determined high systolic blood pressure and high-density lipoprotein (HDL) cholesterol were associated with increased odds of Alzheimer disease (AD) in a large genetic association study, according to study results published online in JAMA Network Open.
“These findings may inspire new drug targeting and improved early dementia prevention,” wrote corresponding author Ruth Frikke-Schmidt, MD, DMSc, PhD, of Copenhagen University Hospital–Rigshospitalet in Copenhagen, Denmark, and coauthors.
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For the study, researchers employed a Mendelian randomization approach that used independent genetic variants associated with modifiable risk factors as instrumental variables. The genomic data sets used in the study are the largest to date and included 39,106 participants with clinically diagnosed AD and 401,577 control participants without AD.
After adjusting for diastolic blood pressure, genetically determined high systolic blood pressure was associated with increased risk of AD. Researchers reported an odds ratio of 1.22 per 10–mm Hg increase.
Additionally, genetically determined high HDL cholesterol concentrations were associated with heightened AD risk, according to the study. The odds ratio was 1.10 per 1-standard deviation increase.
“There was no consistent evidence supporting genetic associations of other lipid traits, body mass index, alcohol consumption, smoking initiation, or diabetes with odds of AD,” researchers wrote.
The study is the first to identify a link between high HDL cholesterol and increased AD risk using a wide range of analyses, researchers pointed out.
“The genetic instruments for HDL cholesterol are marking well-known genes in HDL cholesterol biology, including ATP binding cassette A and G transporters, cholesteryl ester transfer protein, endothelial lipase, hepatic lipase, lipoprotein lipase, and scavenger receptor B1,” they wrote, “further strengthening the validity of our findings.”
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