Genetically elevated high-density lipoprotein cholesterol through the cholesteryl ester transfer protein gene does not associate with risk of Alzheimer's disease

doi:10.1016/j.dadm.2018.08.008

Genetically elevated high-density lipoprotein cholesterol through the cholesteryl ester transfer protein gene does not associate with risk of Alzheimer's disease

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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
Pages (from-to)	595-598
Number of pages	4
Journal	Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring
Volume	10
DOIs	https://doi.org/10.1016/j.dadm.2018.08.008
State	Published - Jan 1 2018

Bibliographical note

Funding Information:
G.M. Peloso is supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health under award number K01HL125751 . S.S. and A.L.D. are supported by grants from the National Institute on Aging : R01 AG054076 , R01 AG033193 , U01 AG049505 , R01 AG008122 (S. Seshadri), and R01AG049607 ) and the National Institute of Neurological Disorders and Stroke ( R01-NS017950 ). The authors thank all the participants and studies contributing to the GLGC and IGAP exome chip results. A full list of collaborators from the IGAP exome chip consortium is listed in the supplement.

Publisher Copyright:
© 2018 The Authors

Keywords

Cholesteryl ester transfer protein
Genetics
HDL-C
Instrumental variables
Single nucleotide polymorphisms

ASJC Scopus subject areas

Clinical Neurology
Psychiatry and Mental health

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.dadm.2018.08.008

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@article{546732b0321f43f2b233f75dfa7cf808,

title = "Genetically elevated high-density lipoprotein cholesterol through the cholesteryl ester transfer protein gene does not associate with risk of Alzheimer's disease",

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.",

keywords = "Cholesteryl ester transfer protein, Genetics, HDL-C, Instrumental variables, Single nucleotide polymorphisms",

author = "Peloso, {Gina M.} and {van der Lee}, {Sven J.} and R. Sims and {van der Lee}, {S. J.} and Naj, {A. C.} and C. Bellenguez and N. Badarinarayan and J. Jakobsdottir and Kunkle, {B. W.} and A. Boland and R. Raybould and Bis, {J. C.} and Martin, {E. R.} and B. Grenier-Boley and S. Heilmann-Heimbach and V. Chouraki and Kuzma, {A. B.} and K. Sleegers and M. Vronskaya and A. Ruiz and Graham, {R. R.} and R. Olaso and P. Hoffmann and Grove, {M. L.} and Vardarajan, {B. N.} and M. Hiltunen and N{\"o}then, {M. M.} and White, {C. C.} and Hamilton-Nelson, {K. L.} and J. Epelbaum and W. Maier and Choi, {S. H.} and Beecham, {G. W.} and C. Dulary and S. Herms and Smith, {A. V.} and Funk, {C. C.} and Derbois and Forstner, {A. J.} and S. Ahmad and H. Li and D. Bacq and D. Harold and Satizabal, {C. L.} and O. Valladares and A. Squassina and R. Thomas and Fardo, {D. W.} and E. Abner and {Van Eldik}, {L. J.}",

note = "Funding Information: G.M. Peloso is supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health under award number K01HL125751 . S.S. and A.L.D. are supported by grants from the National Institute on Aging : R01 AG054076 , R01 AG033193 , U01 AG049505 , R01 AG008122 (S. Seshadri), and R01AG049607 ) and the National Institute of Neurological Disorders and Stroke ( R01-NS017950 ). The authors thank all the participants and studies contributing to the GLGC and IGAP exome chip results. A full list of collaborators from the IGAP exome chip consortium is listed in the supplement. Publisher Copyright: {\textcopyright} 2018 The Authors",

year = "2018",

month = jan,

day = "1",

doi = "10.1016/j.dadm.2018.08.008",

language = "English",

volume = "10",

pages = "595--598",

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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 - 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 - Thomas, R.

AU - Fardo, D. W.

AU - Abner, E.

AU - Van Eldik, L. J.

N1 - Funding Information: G.M. Peloso is supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health under award number K01HL125751 . S.S. and A.L.D. are supported by grants from the National Institute on Aging : R01 AG054076 , R01 AG033193 , U01 AG049505 , R01 AG008122 (S. Seshadri), and R01AG049607 ) and the National Institute of Neurological Disorders and Stroke ( R01-NS017950 ). The authors thank all the participants and studies contributing to the GLGC and IGAP exome chip results. A full list of collaborators from the IGAP exome chip consortium is listed in the supplement. Publisher Copyright: © 2018 The Authors

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

ER -

Genetically elevated high-density lipoprotein cholesterol through the cholesteryl ester transfer protein gene does not associate with risk of Alzheimer's disease

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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