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Genome-wide association study of Alzheimer's disease CSF biomarkers in the EMIF-AD Multimodal Biomarker Discovery dataset

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Harvard

Hong, S, Prokopenko, D, Dobricic, V, Kilpert, F, Bos, I, Vos, SJB, Tijms, BM, Andreasson, U, Blennow, K, Vandenberghe, R, Cleynen, I, Gabel, S, Schaeverbeke, J, Scheltens, P, Teunissen, CE, Niemantsverdriet, E, Engelborghs, S, Frisoni, G, Blin, O, Richardson, JC, Bordet, R, Molinuevo, JL, Rami, L, Kettunen, P, Wallin, A, Lleó, A, Sala, I, Popp, J, Peyratout, G, Martinez-Lage, P, Tainta, M, Dobson, RJB, Legido-Quigley, C, Sleegers, K, Van Broeckhoven, C, Ten Kate, M, Barkhof, F, Zetterberg, H, Lovestone, S, Streffer, J, Wittig, M, Franke, A, Tanzi, RE, Visser, PJ, Bertram, L & Alzheimer’s Disease Neuroimaging Initiative (ADNI) 2020, 'Genome-wide association study of Alzheimer's disease CSF biomarkers in the EMIF-AD Multimodal Biomarker Discovery dataset', Translational psychiatry, bind 10, nr. 1, 403, s. 403. https://doi.org/10.1038/s41398-020-01074-z

APA

Hong, S., Prokopenko, D., Dobricic, V., Kilpert, F., Bos, I., Vos, S. J. B., Tijms, B. M., Andreasson, U., Blennow, K., Vandenberghe, R., Cleynen, I., Gabel, S., Schaeverbeke, J., Scheltens, P., Teunissen, C. E., Niemantsverdriet, E., Engelborghs, S., Frisoni, G., Blin, O., ... Alzheimer’s Disease Neuroimaging Initiative (ADNI) (2020). Genome-wide association study of Alzheimer's disease CSF biomarkers in the EMIF-AD Multimodal Biomarker Discovery dataset. Translational psychiatry, 10(1), 403. [403]. https://doi.org/10.1038/s41398-020-01074-z

CBE

Hong S, Prokopenko D, Dobricic V, Kilpert F, Bos I, Vos SJB, Tijms BM, Andreasson U, Blennow K, Vandenberghe R, Cleynen I, Gabel S, Schaeverbeke J, Scheltens P, Teunissen CE, Niemantsverdriet E, Engelborghs S, Frisoni G, Blin O, Richardson JC, Bordet R, Molinuevo JL, Rami L, Kettunen P, Wallin A, Lleó A, Sala I, Popp J, Peyratout G, Martinez-Lage P, Tainta M, Dobson RJB, Legido-Quigley C, Sleegers K, Van Broeckhoven C, Ten Kate M, Barkhof F, Zetterberg H, Lovestone S, Streffer J, Wittig M, Franke A, Tanzi RE, Visser PJ, Bertram L, Alzheimer’s Disease Neuroimaging Initiative (ADNI). 2020. Genome-wide association study of Alzheimer's disease CSF biomarkers in the EMIF-AD Multimodal Biomarker Discovery dataset. Translational psychiatry. 10(1):403. https://doi.org/10.1038/s41398-020-01074-z

MLA

Vancouver

Author

Hong, Shengjun ; Prokopenko, Dmitry ; Dobricic, Valerija ; Kilpert, Fabian ; Bos, Isabelle ; Vos, Stephanie J B ; Tijms, Betty M ; Andreasson, Ulf ; Blennow, Kaj ; Vandenberghe, Rik ; Cleynen, Isabelle ; Gabel, Silvy ; Schaeverbeke, Jolien ; Scheltens, Philip ; Teunissen, Charlotte E ; Niemantsverdriet, Ellis ; Engelborghs, Sebastiaan ; Frisoni, Giovanni ; Blin, Olivier ; Richardson, Jill C ; Bordet, Regis ; Molinuevo, José Luis ; Rami, Lorena ; Kettunen, Petronella ; Wallin, Anders ; Lleó, Alberto ; Sala, Isabel ; Popp, Julius ; Peyratout, Gwendoline ; Martinez-Lage, Pablo ; Tainta, Mikel ; Dobson, Richard J B ; Legido-Quigley, Cristina ; Sleegers, Kristel ; Van Broeckhoven, Christine ; Ten Kate, Mara ; Barkhof, Frederik ; Zetterberg, Henrik ; Lovestone, Simon ; Streffer, Johannes ; Wittig, Michael ; Franke, Andre ; Tanzi, Rudolph E ; Visser, Pieter Jelle ; Bertram, Lars ; Alzheimer’s Disease Neuroimaging Initiative (ADNI). / Genome-wide association study of Alzheimer's disease CSF biomarkers in the EMIF-AD Multimodal Biomarker Discovery dataset. I: Translational psychiatry. 2020 ; Bind 10, Nr. 1. s. 403.

Bibtex

@article{25a55d4110f14eb592ddd6f77fc377d4,
title = "Genome-wide association study of Alzheimer's disease CSF biomarkers in the EMIF-AD Multimodal Biomarker Discovery dataset",
abstract = "Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder and the most common form of dementia in the elderly. Susceptibility to AD is considerably determined by genetic factors which hitherto were primarily identified using case-control designs. Elucidating the genetic architecture of additional AD-related phenotypic traits, ideally those linked to the underlying disease process, holds great promise in gaining deeper insights into the genetic basis of AD and in developing better clinical prediction models. To this end, we generated genome-wide single-nucleotide polymorphism (SNP) genotyping data in 931 participants of the European Medical Information Framework Alzheimer's Disease Multimodal Biomarker Discovery (EMIF-AD MBD) sample to search for novel genetic determinants of AD biomarker variability. Specifically, we performed genome-wide association study (GWAS) analyses on 16 traits, including 14 measures derived from quantifications of five separate amyloid-beta (Aβ) and tau-protein species in the cerebrospinal fluid (CSF). In addition to confirming the well-established effects of apolipoprotein E (APOE) on diagnostic outcome and phenotypes related to Aβ42, we detected novel potential signals in the zinc finger homeobox 3 (ZFHX3) for CSF-Aβ38 and CSF-Aβ40 levels, and confirmed the previously described sex-specific association between SNPs in geminin coiled-coil domain containing (GMNC) and CSF-tau. Utilizing the results from independent case-control AD GWAS to construct polygenic risk scores (PRS) revealed that AD risk variants only explain a small fraction of CSF biomarker variability. In conclusion, our study represents a detailed first account of GWAS analyses on CSF-Aβ and -tau-related traits in the EMIF-AD MBD dataset. In subsequent work, we will utilize the genomics data generated here in GWAS of other AD-relevant clinical outcomes ascertained in this unique dataset.",
keywords = "Aged, Alzheimer Disease/genetics, Amyloid beta-Peptides/genetics, Biomarkers, Female, Genome-Wide Association Study, Humans, Male, Peptide Fragments, tau Proteins/genetics",
author = "Shengjun Hong and Dmitry Prokopenko and Valerija Dobricic and Fabian Kilpert and Isabelle Bos and Vos, {Stephanie J B} and Tijms, {Betty M} and Ulf Andreasson and Kaj Blennow and Rik Vandenberghe and Isabelle Cleynen and Silvy Gabel and Jolien Schaeverbeke and Philip Scheltens and Teunissen, {Charlotte E} and Ellis Niemantsverdriet and Sebastiaan Engelborghs and Giovanni Frisoni and Olivier Blin and Richardson, {Jill C} and Regis Bordet and Molinuevo, {Jos{\'e} Luis} and Lorena Rami and Petronella Kettunen and Anders Wallin and Alberto Lle{\'o} and Isabel Sala and Julius Popp and Gwendoline Peyratout and Pablo Martinez-Lage and Mikel Tainta and Dobson, {Richard J B} and Cristina Legido-Quigley and Kristel Sleegers and {Van Broeckhoven}, Christine and {Ten Kate}, Mara and Frederik Barkhof and Henrik Zetterberg and Simon Lovestone and Johannes Streffer and Michael Wittig and Andre Franke and Tanzi, {Rudolph E} and Visser, {Pieter Jelle} and Lars Bertram and {Alzheimer{\textquoteright}s Disease Neuroimaging Initiative (ADNI)}",
year = "2020",
month = dec,
day = "22",
doi = "10.1038/s41398-020-01074-z",
language = "English",
volume = "10",
pages = "403",
journal = "Translational Psychiatry",
issn = "2158-3188",
publisher = "Nature Publishing Group",
number = "1",

}

RIS

TY - JOUR

T1 - Genome-wide association study of Alzheimer's disease CSF biomarkers in the EMIF-AD Multimodal Biomarker Discovery dataset

AU - Hong, Shengjun

AU - Prokopenko, Dmitry

AU - Dobricic, Valerija

AU - Kilpert, Fabian

AU - Bos, Isabelle

AU - Vos, Stephanie J B

AU - Tijms, Betty M

AU - Andreasson, Ulf

AU - Blennow, Kaj

AU - Vandenberghe, Rik

AU - Cleynen, Isabelle

AU - Gabel, Silvy

AU - Schaeverbeke, Jolien

AU - Scheltens, Philip

AU - Teunissen, Charlotte E

AU - Niemantsverdriet, Ellis

AU - Engelborghs, Sebastiaan

AU - Frisoni, Giovanni

AU - Blin, Olivier

AU - Richardson, Jill C

AU - Bordet, Regis

AU - Molinuevo, José Luis

AU - Rami, Lorena

AU - Kettunen, Petronella

AU - Wallin, Anders

AU - Lleó, Alberto

AU - Sala, Isabel

AU - Popp, Julius

AU - Peyratout, Gwendoline

AU - Martinez-Lage, Pablo

AU - Tainta, Mikel

AU - Dobson, Richard J B

AU - Legido-Quigley, Cristina

AU - Sleegers, Kristel

AU - Van Broeckhoven, Christine

AU - Ten Kate, Mara

AU - Barkhof, Frederik

AU - Zetterberg, Henrik

AU - Lovestone, Simon

AU - Streffer, Johannes

AU - Wittig, Michael

AU - Franke, Andre

AU - Tanzi, Rudolph E

AU - Visser, Pieter Jelle

AU - Bertram, Lars

AU - Alzheimer’s Disease Neuroimaging Initiative (ADNI)

PY - 2020/12/22

Y1 - 2020/12/22

N2 - Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder and the most common form of dementia in the elderly. Susceptibility to AD is considerably determined by genetic factors which hitherto were primarily identified using case-control designs. Elucidating the genetic architecture of additional AD-related phenotypic traits, ideally those linked to the underlying disease process, holds great promise in gaining deeper insights into the genetic basis of AD and in developing better clinical prediction models. To this end, we generated genome-wide single-nucleotide polymorphism (SNP) genotyping data in 931 participants of the European Medical Information Framework Alzheimer's Disease Multimodal Biomarker Discovery (EMIF-AD MBD) sample to search for novel genetic determinants of AD biomarker variability. Specifically, we performed genome-wide association study (GWAS) analyses on 16 traits, including 14 measures derived from quantifications of five separate amyloid-beta (Aβ) and tau-protein species in the cerebrospinal fluid (CSF). In addition to confirming the well-established effects of apolipoprotein E (APOE) on diagnostic outcome and phenotypes related to Aβ42, we detected novel potential signals in the zinc finger homeobox 3 (ZFHX3) for CSF-Aβ38 and CSF-Aβ40 levels, and confirmed the previously described sex-specific association between SNPs in geminin coiled-coil domain containing (GMNC) and CSF-tau. Utilizing the results from independent case-control AD GWAS to construct polygenic risk scores (PRS) revealed that AD risk variants only explain a small fraction of CSF biomarker variability. In conclusion, our study represents a detailed first account of GWAS analyses on CSF-Aβ and -tau-related traits in the EMIF-AD MBD dataset. In subsequent work, we will utilize the genomics data generated here in GWAS of other AD-relevant clinical outcomes ascertained in this unique dataset.

AB - Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder and the most common form of dementia in the elderly. Susceptibility to AD is considerably determined by genetic factors which hitherto were primarily identified using case-control designs. Elucidating the genetic architecture of additional AD-related phenotypic traits, ideally those linked to the underlying disease process, holds great promise in gaining deeper insights into the genetic basis of AD and in developing better clinical prediction models. To this end, we generated genome-wide single-nucleotide polymorphism (SNP) genotyping data in 931 participants of the European Medical Information Framework Alzheimer's Disease Multimodal Biomarker Discovery (EMIF-AD MBD) sample to search for novel genetic determinants of AD biomarker variability. Specifically, we performed genome-wide association study (GWAS) analyses on 16 traits, including 14 measures derived from quantifications of five separate amyloid-beta (Aβ) and tau-protein species in the cerebrospinal fluid (CSF). In addition to confirming the well-established effects of apolipoprotein E (APOE) on diagnostic outcome and phenotypes related to Aβ42, we detected novel potential signals in the zinc finger homeobox 3 (ZFHX3) for CSF-Aβ38 and CSF-Aβ40 levels, and confirmed the previously described sex-specific association between SNPs in geminin coiled-coil domain containing (GMNC) and CSF-tau. Utilizing the results from independent case-control AD GWAS to construct polygenic risk scores (PRS) revealed that AD risk variants only explain a small fraction of CSF biomarker variability. In conclusion, our study represents a detailed first account of GWAS analyses on CSF-Aβ and -tau-related traits in the EMIF-AD MBD dataset. In subsequent work, we will utilize the genomics data generated here in GWAS of other AD-relevant clinical outcomes ascertained in this unique dataset.

KW - Aged

KW - Alzheimer Disease/genetics

KW - Amyloid beta-Peptides/genetics

KW - Biomarkers

KW - Female

KW - Genome-Wide Association Study

KW - Humans

KW - Male

KW - Peptide Fragments

KW - tau Proteins/genetics

UR - http://www.scopus.com/inward/record.url?scp=85096381015&partnerID=8YFLogxK

U2 - 10.1038/s41398-020-01074-z

DO - 10.1038/s41398-020-01074-z

M3 - Journal article

C2 - 33223526

VL - 10

SP - 403

JO - Translational Psychiatry

JF - Translational Psychiatry

SN - 2158-3188

IS - 1

M1 - 403

ER -

ID: 61376178