Introduction: There is conflicting evidence whether high-density lipoprotein cholesterol (HDL-C) is a risk factor for Alzheimer's disease (AD) and dementia. Genetic variation in the cholesteryl ester transfer protein (CETP) locus is associated with altered HDL-C. We aimed to assess AD risk by genetically predicted HDL-C. Methods: Ten single nucleotide polymorphisms within the CETP locus predicting HDL-C were applied to the International Genomics of Alzheimer's Project (IGAP) exome chip stage 1 results in up 16,097 late onset AD cases and 18,077 cognitively normal elderly controls. We performed instrumental variables analysis using inverse variance weighting, weighted median, and MR-Egger. Results: Based on 10 single nucleotide polymorphisms distinctly predicting HDL-C in the CETP locus, we found that HDL-C was not associated with risk of AD (P >.7). Discussion: Our study does not support the role of HDL-C on risk of AD through HDL-C altered by CETP. This study does not rule out other mechanisms by which HDL-C affects risk of AD.

Additional Metadata
Keywords Cholesteryl ester transfer protein, Genetics, HDL-C, Instrumental variables, Single nucleotide polymorphisms
Persistent URL dx.doi.org/10.1016/j.dadm.2018.08.008, hdl.handle.net/1765/111737
Journal Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring
Citation
Peloso, G.M. (Gina M.), van der Lee, S.J, Sims, R, van der Lee, S.J. (S. J.), Naj, A.C. (A. C.), Bellenguez, C, … Seshardi, S. (Sudha). (2018). Genetically elevated high-density lipoprotein cholesterol through the cholesteryl ester transfer protein gene does not associate with risk of Alzheimer's disease. Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring, 10, 595–598. doi:10.1016/j.dadm.2018.08.008