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Explorative results from multistep screening for potential genetic risk loci of Alzheimer’s disease in the longitudinal VITA study cohort

  • Neurology and Preclinical Neurological Studies - Original Article
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Abstract

Alzheimer’s disease (AD) is a neurodegenerative disorder that preferentially affects individuals of advanced age. Heritability estimates for AD range between 60 and 80%, but only few genetic risk factors have been identified so far. In the present explorative study, we aimed at characterizing the genetic contribution to late-onset AD in participants of the Vienna Transdanube Aging (VITA) longitudinal birth cohort study in a two-step approach. First, we performed a genome-wide screen of pooled DNA samples (n = 588) to identify allele frequency differences between AD patients and non-AD individuals using life-time diagnoses made at the age of 80 (t = 60 months). This analysis suggested a high proportion of brain-expressed genes required for cell adhesion, cell signaling and cell morphogenesis, and also scored in known AD risk genes. In a second step, we confirmed associations using individual genotypes of top-ranked markers examining AD diagnoses as well as the dimensional scores: FULD and MMSE determined up to the age of 82.5 (t = 90 months). Taken together, our study proposes genes ANKS1B, ENST00000414107, LOC100505811, SLC22A14, QRFPR, ZDHHC8P1, ADAMTS3 and PPFIA1 as possible new candidates involved in the etiology of late-onset AD, with further research being needed to clarify their exact roles.

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Acknowledgements

We thank all participants of the VITA study and their families. We credit the excellent technical assistance of Miryame Hofmann, Terri Töppner and Margarete Göbel.

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Authors and Affiliations

  1. Core Unit Systems Medicine, University Hospital of Würzburg, Würzburg, Germany

    Claus-Jürgen Scholz

  2. Department of Psychiatry, Psychosomatics, Psychotherapy, University Hospital Frankfurt/Main, Frankfurt/Main, Germany

    Heike Weber & Andreas Reif

  3. Center of Mental Health, Clinic and Policlinic of Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Würzburg, Würzburg, Germany

    Heike Weber, Peter Riederer, Jürgen Deckert & Edna Grünblatt

  4. Ludwig Boltzmann Society, L. Boltzmann Institute of Aging Research, Vienna, Austria

    Susanne Jungwirth, Walter Danielczyk, Karl-Heinz Tragl & Peter Fischer

  5. Department of Psychiatry, Social Medicine Center East- Donauspital, Vienna, Austria

    Susanne Jungwirth & Peter Fischer

  6. Department of Child and Adolescent Psychiatry and Psychotherapy, University Hospital of Psychiatry Zurich, University of Zurich, Wagistrasse 12, Schlieren, 8952, Zurich, Switzerland

    Edna Grünblatt

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  1. Claus-Jürgen Scholz
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  2. Heike Weber
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  3. Susanne Jungwirth
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  4. Walter Danielczyk
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  6. Karl-Heinz Tragl
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  7. Peter Fischer
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  8. Peter Riederer
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  9. Jürgen Deckert
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  10. Edna Grünblatt
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Contributions

CJS and HW performed data analysis; SJ, WD, KHT and PF were involved in participant recruitment and coordinated the cohort study; HW and AR generated genotyping data; PR, JD and EG supervised the study, CJS, JD and EG wrote the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Edna Grünblatt.

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Informed consent

The VITA study was carried out with the permission of the Ethics Committee of the City of Vienna, Austria and conforms to the Declaration of Helsinki; each participant provided written informed consent.

Conflict of interest

The authors declare that they have no competing interests.

Funding

This work has been funded by the Ludwig Boltzmann Institute of Aging Research (Vienna, Austria) and the Alzheimer Forschung Initiative e.V. (AFI) with Grant 09802 to EG. CJS is supported by the Interdisziplinäres Zentrum für Klinische Forschung (IZKF) Grant Z-6.

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Scholz, CJ., Weber, H., Jungwirth, S. et al. Explorative results from multistep screening for potential genetic risk loci of Alzheimer’s disease in the longitudinal VITA study cohort. J Neural Transm 125, 77–87 (2018). https://doi.org/10.1007/s00702-017-1796-6

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  • DOI: https://doi.org/10.1007/s00702-017-1796-6

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