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  • Brief Communications Arising
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PLD3 in non-familial Alzheimer's disease

Nature volume 520, pages E3–E5 (2015)Cite this article

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arising from C. Cruchaga et al. Nature 505, 550–554 (2014); doi:10.1038/nature12825

Interest in the role of rare genetic variants in the aetiology of complex diseases such as Alzheimer's disease is increasing1,2. Recently, Cruchaga et al.3 provided evidence supporting the role of rare variants in the phospholipase D3 (PLD3) gene in both familial late-onset Alzheimer's disease (age at onset >65 years) and in non-familial Alzheimer's disease. In a follow-up study of 3,568 non-familial Alzheimer's disease cases and 3,867 controls of German or Spanish descent, we failed to replicate the latter finding. Our results therefore cast doubt on the aetiological relevance of rare coding PLD3 variants in non-familial Alzheimer's disease. There is a Reply to this Brief Communication Arising by Cruchaga, C. & Goate, A. M. Nature 520, http://dx.doi.org/10.1038/nature14037 (2015).

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Authors and Affiliations

  1. Institute of Human Genetics, University of Bonn, Bonn, 53127, Germany

    Stefanie Heilmann, Markus M. Nöthen & Alfredo Ramirez

  2. Department of Genomics, Life & Brain Center, University of Bonn, Bonn, 53127, Germany

    Stefanie Heilmann & Markus M. Nöthen

  3. German Center for Neurodegenerative Diseases (DZNE), Bonn, 53175, Germany

    Dmitriy Drichel, André Lacour, Michael T. Heneka, Frank Jessen, Tim Becker & Wolfgang Maier

  4. Neurology Department and Sant Pau Biomedical Research Institute, Memory Unit, Hospital Santa Creu i Sant Pau, Autonomous University Barcelona, Barcelona, 08025, Spain

    Jordi Clarimon, Juan Fortea, Rafael Blesa & Alberto Lleó

  5. Center for Networking Biomedical Research in Neurodegenerative Diseases (CIBERNED), Madrid, 28029, Spain

    Jordi Clarimon, Juan Fortea, Rafael Blesa & Alberto Lleó

  6. Memory Clinic of Fundaciò ACE, Catalan Institute of Applied Neurosciences, Barcelona, 08028, Spain

    Victoria Fernández, Isabel Hernández, Montserrat Alegret, Ana Mauleón, Maitée Rosende Roca, Lluís Tárraga, Mercè Boada & Agustin Ruiz

  7. Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, 53127, Germany

    Holger Wagner, Mathias Thelen, Reinhard Heun, Frank Jessen, Wolfgang Maier & Alfredo Ramirez

  8. Department of Psychiatry and Psychotherapy, University Clinic Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, 91054, Germany

    Johannes Kornhuber

  9. Department of Psychiatry, Charité University Medicine, Berlin, 14050, Germany

    Oliver Peters

  10. Department of Geriatric Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, 68159, Germany

    Lutz Frölich

  11. Centre for Geriatric Medicine and Section of Gerontopsychiatry and Neuropsychology, Medical School, University of Freiburg, Freiburg, 79106, Germany

    Michael Hüll

  12. Department of Neurology, Clinical Neuroscience Unit, University of Bonn, Bonn, 53127, Germany

    Michael T. Heneka

  13. Department of Psychiatry and Psychotherapy, University of Göttingen, Göttingen, 37075, Germany

    Eckart Rüther & Jens Wiltfang

  14. Institute of Social Medicine, Occupational Health and Public Health, University of Leipzig, Leipzig, 04103, Germany

    Steffi Riedel-Heller

  15. Department of Primary Medical Care, University Medical Centre Hamburg-Eppendorf, Hamburg, 20246, Germany

    Martin Scherer

  16. Department of Psychiatry and Psychotherapy, University of Cologne, Cologne, 50937, Germany

    Frank Jessen

  17. Institute for Medical Biometry, Informatics and Epidemiology, University of Bonn, Bonn, 53127, Germany

    Tim Becker

Authors
  1. Stefanie Heilmann
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Contributions

Data collection: J.C., I.H., J.F., M.A., R.B., A.M., M.R.R., J.K., O.P., R.H., L.F., M.H., M.T.H., E.R., S.R.H., M.S., J.W., F.J., L.T., M.B., Al.L.; experimental work: S.H., V.F., A.L., H.W., M.T.; project planning: Ag.R., Al.R., J.C., T.B., S.H., M.M.N.; data analysis: S.H., D.D., An.L., T.B., Al.R., J.C., Ag.R.; administrative, technical or material support: J.C., An.L., H.W., M.T., I.H., J.F., M.A., R.B., A.M., M.R.R., J.K., O.P., M.S., L.T., M.B., W.M., Al.L., Ag.R., Al.R.; critical revision of the manuscript for important intellectual content: S.H., D.D., J.C., V.F., An.L., H.W., M.T., I.H., J.F., M.A., R.B., A.M., M.R.R., J.K., O.P., R.H., L.F., M.H., M.T.H., E.R., S.R.H., M.S., J.W., F.J., T.B., L.T., M.B., W.M., Al.L., Ag.R., M.M.N., Al.R.; drafting of the manuscript: Al.R., M.M.N., S.H., T.B., D.D., Ag.R., J.C.; obtaining funding: W.M., M.M.N., F.J., M.S., M.B., L.T., Ag.R., T.B. and J.C.

Corresponding author

Correspondence to Alfredo Ramirez.

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Heilmann, S., Drichel, D., Clarimon, J. et al. PLD3 in non-familial Alzheimer's disease. Nature 520, E3–E5 (2015). https://doi.org/10.1038/nature14039

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