Genetically elevated high-density lipoprotein cholesterol through the cholesteryl ester transfer protein gene does not associate with risk of Alzheimer's disease
Peloso GM., van der Lee SJ., Sims R., van der Lee SJ., Naj AC., Bellenguez C., Badarinarayan N., Jakobsdottir J., Kunkle BW., Boland A., Raybould R., Bis JC., Martin ER., Grenier-Boley B., Heilmann-Heimbach S., Chouraki V., Kuzma AB., Sleegers K., Vronskaya M., Ruiz A., Graham RR., Olaso R., Hoffmann P., Grove ML., Vardarajan BN., Hiltunen M., Nöthen MM., White CC., Hamilton-Nelson KL., Epelbaum J., Maier W., Choi SH., Beecham GW., Dulary C., Herms S., Smith AV., Funk CC., Derbois None., Forstner AJ., Ahmad S., Li H., Bacq D., Harold D., Satizabal CL., Valladares O., Squassina A., Thomas R., Brody JA., Qu L., Sánchez-Juan P., Morgan T., Wolters FJ., Zhao Y., Garcia FS., Denning N., Fornage M., Malamon J., Naranjo MCD., Majounie E., Mosley TH., Dombroski B., Wallon D., Lupton MK., Dupuis J., Whitehead P., Fratiglioni L., Medway C., Jian X., Mukherjee S., Keller L., Brown K., Lin H., Cantwell LB., Panza F., McGuinness B., Moreno-Grau S., Burgess JD., Solfrizzi V., Proitsi P., Adams HH., Allen M., Seripa D., Pastor P., Cupples LA., Price ND., Hannequin D., Frank-García A., Levy D., Chakrabarty P., Caffarra P., Giegling I., Beiser AS., Giedraitis V., Hampel H., Garcia ME., Wang X., Lannfelt L., Mecocci P., Eiriksdottir G., Crane PK.
© 2018 The Authors 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.