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  • Brief Communications Arising
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PLD3 variants in population studies

Nature volume 520, pages E2–E3 (2015)Cite this article

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

Cruchaga et al.1 reported that rare genetic variants in phospholipase D3 (PLD3) are associated with increased Alzheimer's disease risk, and showed that PLD3 is involved in amyloid-β precursor protein processing and is overexpressed in brain tissue from Alzheimer's disease patients; however, the key variant PLD3 Val232Met did not pass genome-wide significance. This observation raises questions whether the genetic association of PLD3 with Alzheimer's disease replicates. We associated PLD3 Val232Met with Alzheimer's disease in three large population-based studies and three case–control studies. In total, we performed a meta-analysis of results from 1,914 Alzheimer's disease cases and 8,021 controls of European descent; furthermore, we searched for other coding PLD3 variants in sequence data of 1,067 Alzheimer's disease cases and 1,553 controls. 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. Department of Epidemiology, Erasmus Medical Center, Rotterdam, 3000, CA, The Netherlands

    Sven J. van der Lee, Najaf Amin, Andre G. Uitterlinden, Albert Hofman, M. Arfan Ikram & Cornelia M. van Duijn

  2. Department of Neurology, Alzheimer Center, VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam, 1081, HZ, The Netherlands

    Henne Holstege, Yolande A. L. Pijnenburg, Eva Louwersheimer, Philip Scheltens, John C. van Swieten & Wiesje M. van der Flier

  3. Department of Clinical Genetics, VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam, 1081, HZ, The Netherlands

    Henne Holstege

  4. Department of Neurology, Erasmus Medical Center, Rotterdam, 3000, CA, The Netherlands

    Tsz Hang Wong, John C. van Swieten & M. Arfan Ikram

  5. Icelandic Heart Association, Kopavogur 201, Iceland

    Johanna Jakobsdottir, Albert V. Smith, Gudny Eirkisdottir, Valur Emilsson, Thor Aspelund & Vilmundur Gudnason

  6. Department of Medicine, Cardiovascular Health Research Unit, University of Washington, Seattle, 98101, Washington, USA

    Joshua C. Bis & Bruce M. Psaty

  7. National Heart, Lung and Blood Institute Framingham Heart Study, Framingham, 01702-5827, Massachusetts, USA

    Vincent Chouraki, Seung-Hoan Choi, Alexa S. Beiser, Daniel Levy, Christopher J. O'Donnell, Anita L. DeStefano & Sudha Seshadri

  8. Boston University School of Medicine, Boston, 02118, Massachusetts, USA

    Vincent Chouraki, Daniel Levy & Sudha Seshadri

  9. Department of Internal Medicine, Erasmus Medical Center, Rotterdam, 3000, CA, The Netherlands

    Jeroen G. J. van Rooij & Andre G. Uitterlinden

  10. School of Public Health, Human Genetics Center, University of Texas Health Science Center at Houston, Houston, 77030, Texas, USA

    Megan L. Grove & Eric Boerwinkle

  11. Faculty of Medicine, University of Iceland, Reykjavik 101, Iceland

    Albert V. Smith & Vilmundur Gudnason

  12. Department of Biostatistics, Boston University School of Public Health, Boston, 02118, Massachusetts, USA

    Seung-Hoan Choi, Alexa S. Beiser & Anita L. DeStefano

  13. Laboratory of Epidemiology and Population Sciences, National Institute on Aging, Bethesda, 20892, Maryland, USA

    Melissa E. Garcia & Lenore J. Launer

  14. Center for Biomics, Erasmus Medical Center, Rotterdam, 3000, CA, The Netherlands

    Wilfred F. J. van IJcken, Rutger W. W. Brouwer, Mirjam C. G. N. van den Hout & Edwin Oole

  15. National Heart, Lung, and Blood Institute, Intramural Research Program, National Institutes of Health, Bethesda, 20892, Maryland, USA

    Daniel Levy & Christopher J. O'Donnell

  16. Institute for Translational Genomics and Population Sciences, Los Angeles BioMedical Research Institute at Harbor-UCLA Medical Center, Torrance, 90502, California, USA

    Jerome I. Rotter

  17. Faculty of Pharmaceutical Sciences, University of Iceland, Reykjavik 101, Iceland

    Valur Emilsson

  18. Centre for Public Health, University of Iceland, Reykjavik 101, Iceland

    Thor Aspelund

  19. Netherlands Consortium on Health Aging and National Genomics Initiative, Leiden, 2300, RC, The Netherlands

    Andre G. Uitterlinden

  20. Human Genome Sequencing Center, Baylor College of Medicine, Houston, 77030, Texas, USA

    Eric Boerwinkle

  21. Department of Epidemiology, University of Washington, Seattle, 98101, Washington, USA

    Bruce M. Psaty

  22. Group Health Research Institute, Seattle, 98101-1448, Washington, USA

    Bruce M. Psaty

  23. Department of Epidemiology & Biostatistics, VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam 1081 HZ, The Netherlands

    Wiesje M. van der Flier

  24. Departments of Radiology, Erasmus Medical Center, Rotterdam, 3000, CA, The Netherlands

    M. Arfan Ikram

Authors
  1. Sven J. van der Lee
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  2. Henne Holstege
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  18. Mirjam C. G. N. van den Hout
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  25. Thor Aspelund
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  26. Andre G. Uitterlinden
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  27. Lenore J. Launer
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  28. Albert Hofman
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  31. Anita L. DeStefano
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  32. Philip Scheltens
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  33. Sudha Seshadri
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  34. John C. van Swieten
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  35. Vilmundur Gudnason
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  36. Wiesje M. van der Flier
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  37. M. Arfan Ikram
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  38. Cornelia M. van Duijn
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Contributions

Study design: C.M.v.D.; acquisition of phenotype and genotype data: H.H., T.H.W., J.G.J.v.R., A.V.S., S.-H.C., A.S.B., M.E.G., W.F.J.v.IJ., Y.A.L.P., E.L., R.W.W.B., M.C., G.N.v.d.H., E.O., G.E., D.L., J.I.R., V.E., C.J.O., T.A., A.G.U., L.J.L., A.H., E.B., B.M.P., A.L.D., P.S., S.S., J.C.v.S., V.G., W.M.v.d.F., M.A.I., C.M.v.D.; data analysis: S.J.v.d.L, H.H., T.H.W., J.J., J.C.B., V.C., N.A. The manuscript was drafted by S.J.v.d.L., N.A., M.A.I., C.M.v.D.; all authors reviewed the manuscript.

Corresponding author

Correspondence to Cornelia M. van Duijn.

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Cite this article

van der Lee, S., Holstege, H., Wong, T. et al. PLD3 variants in population studies. Nature 520, E2–E3 (2015). https://doi.org/10.1038/nature14038

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