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

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Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_FC0401585DE0
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Genome-wide association study of Alzheimer's disease CSF biomarkers in the EMIF-AD Multimodal Biomarker Discovery dataset.
Journal
Translational psychiatry
Author(s)
Hong S., Prokopenko D., Dobricic V., Kilpert F., Bos I., Vos SJB, 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., Richardson J.C., Bordet R., Molinuevo J.L., 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 R.E., Visser P.J., Bertram L.
Working group(s)
Alzheimer's Disease Neuroimaging Initiative (ADNI)
ISSN
2158-3188 (Electronic)
ISSN-L
2158-3188
Publication state
Published
Issued date
22/11/2020
Peer-reviewed
Oui
Volume
10
Number
1
Pages
403
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
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.
Pubmed
Web of science
Open Access
Yes
Create date
26/11/2020 23:00
Last modification date
30/04/2021 6:16
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