Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 595-598 |
| Number of pages | 4 |
| Journal | Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring |
| Volume | 10 |
| DOIs | |
| State | Published - Jan 1 2018 |
Fingerprint
Keywords
- Cholesteryl ester transfer protein
- Genetics
- HDL-C
- Instrumental variables
- Single nucleotide polymorphisms
ASJC Scopus subject areas
- Clinical Neurology
- Psychiatry and Mental health
Cite this
Genetically elevated high-density lipoprotein cholesterol through the cholesteryl ester transfer protein gene does not associate with risk of Alzheimer's disease. / International Genomics of Alzheimer's Project (IGAP); ARUK Consortium; GERAD/PERADES, CHARGE, ADGC, EADI.
In: Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring, Vol. 10, 01.01.2018, p. 595-598.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Genetically elevated high-density lipoprotein cholesterol through the cholesteryl ester transfer protein gene does not associate with risk of Alzheimer's disease
AU - International Genomics of Alzheimer's Project (IGAP)
AU - ARUK Consortium
AU - GERAD/PERADES, CHARGE, ADGC, EADI
AU - Peloso, Gina M.
AU - van der Lee, Sven J.
AU - Sims, R.
AU - van der Lee, S. J.
AU - Naj, A. C.
AU - Bellenguez, C.
AU - Badarinarayan, N.
AU - Jakobsdottir, J.
AU - Kunkle, B. W.
AU - Boland, A.
AU - Raybould, R.
AU - Bis, J. C.
AU - Martin, E. R.
AU - Grenier-Boley, B.
AU - Heilmann-Heimbach, S.
AU - Chouraki, V.
AU - Kuzma, A. B.
AU - Sleegers, K.
AU - Vronskaya, M.
AU - Ruiz, A.
AU - Graham, R. R.
AU - Olaso, R.
AU - Hoffmann, P.
AU - Grove, M. L.
AU - Vardarajan, B. N.
AU - Hiltunen, M.
AU - Nöthen, M. M.
AU - White, C. C.
AU - Hamilton-Nelson, K. L.
AU - Epelbaum, J.
AU - Maier, W.
AU - Choi, S. H.
AU - Beecham, G. W.
AU - Dulary, C.
AU - Herms, S.
AU - Smith, A. V.
AU - Funk, C. C.
AU - Derbois,
AU - Forstner, A. J.
AU - Ahmad, S.
AU - Li, H.
AU - Bacq, D.
AU - Harold, D.
AU - Satizabal, C. L.
AU - Valladares, O.
AU - Squassina, A.
AU - Kaye, Jeffrey
AU - Pierce, Aimee
AU - Quinn, Joseph
AU - Woltjer, Randall (Randy)
PY - 2018/1/1
Y1 - 2018/1/1
N2 - 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.
AB - 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.
KW - Cholesteryl ester transfer protein
KW - Genetics
KW - HDL-C
KW - Instrumental variables
KW - Single nucleotide polymorphisms
UR - http://www.scopus.com/inward/record.url?scp=85055648674&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85055648674&partnerID=8YFLogxK
U2 - 10.1016/j.dadm.2018.08.008
DO - 10.1016/j.dadm.2018.08.008
M3 - Article
AN - SCOPUS:85055648674
VL - 10
SP - 595
EP - 598
JO - Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring
JF - Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring
SN - 2352-8729
ER -