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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Resumen

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.

Idioma original	English
Páginas (desde-hasta)	595-598
Número de páginas	4
Publicación	Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring
Volumen	10
DOI	https://doi.org/10.1016/j.dadm.2018.08.008
Estado	Published - ene 1 2018

Nota bibliográfica

Publisher Copyright:
© 2018 The Authors

Financiación

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.

Financiadores	Número del financiador
National Institutes of Health (NIH)
National Institute on Aging	R01 AG054076, R01 AG033193, U01 AG049505, R01AG049607, R01 AG008122
National Heart, Lung, and Blood Institute (NHLBI)	K01HL125751
Institute of Neurological Disorders and Stroke National Advisory Neurological Disorders and Stroke Council	R01-NS017950
UK Medical Research Council, Engineering and Physical Sciences Research Council	MR/R024804/1

ODS de las Naciones Unidas

Este resultado contribuye a los siguientes Objetivos de Desarrollo Sostenible

Good health and well being

ASJC Scopus subject areas

Clinical Neurology
Psychiatry and Mental health

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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 = "Publisher Copyright: {\textcopyright} 2018 The Authors",

year = "2018",

month = jan,

day = "1",

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

language = "English",

volume = "10",

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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.

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 - https://www.scopus.com/pages/publications/85055648674

UR - https://www.scopus.com/pages/publications/85055648674#tab=citedBy

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

ER -

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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Financiación

ODS de las Naciones Unidas

ASJC Scopus subject areas

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