Excess of rare coding variants in PLD3 in late- but not early-onset Alzheimer's disease

Eva C Schulte; Alexander Kurz; Panagiotis Alexopoulos; Harald Hampel; Annette Peters; Christian Gieger; Dan Rujescu; Janine Diehl-Schmid; Juliane Winkelmann

doi:10.1038/hgv.2014.28

Excess of rare coding variants in PLD3 in late- but not early-onset Alzheimer's disease

Hum Genome Var. 2015 Jan 9:2:14028. doi: 10.1038/hgv.2014.28. eCollection 2015.

Authors

Eva C Schulte¹, Alexander Kurz², Panagiotis Alexopoulos², Harald Hampel³, Annette Peters⁴, Christian Gieger⁵, Dan Rujescu⁶, Janine Diehl-Schmid², Juliane Winkelmann⁷

Affiliations

¹ Neurologische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany; Institut für Humangenetik, Helmholtz Zentrum München, Neuherberg, Germany.
² Klinik und Poliklinik für Psychiatrie und Psychotherapie, Klinikum rechts der Isar, Technische Universität München , Munich, Germany.
³ AXA Research Fund; Sorbonne Universités, Université Pierre et Marie Curie, Paris 06, Institut de la Mémoire et de la Maladie d'Alzheimer (IM2A) & Institut du Cerveau et de la Moelle épinière (ICM), Département de Neurologie, Hôpital de la Pitié-Salpétrière, Paris, France; Université Pierre et Marie Curie-Paris 6, AP-HP, Hôpital de la Salpêtrière, Paris, France.
⁴ Institute of Epidemiology II, Helmholtz Zentrum München , Neuherberg, Germany.
⁵ Institute of Genetic Epidemiology, Helmholtz Zentrum München , Neuherberg, Germany.
⁶ Klinik für Psychiatrie, Universität Halle , Halle, Germany.
⁷ Neurologische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany; Institut für Humangenetik, Helmholtz Zentrum München, Neuherberg, Germany; Institut für Humangenetik, Technische Universität München, Munich, Germany; Munich Cluster for Systems Neurology (SyNergy), Munich, Germany; Department of Neurology and Neurosciences, Stanford University, Palo Alto, CA, USA.

Abstract

Recently, mutations in phospholipase D3 (PLD3) were reported in late-onset Alzheimer's disease (AD). By screening the coding regions of PLD3 for variants in a European cohort of 1,089 AD cases, 182 individuals with frontotemporal lobar degeneration and 1,456 controls, we identified 32 variants with a minor allele frequency <5% and observed an excess of rare variants in individuals with late- but not early-onset AD (P=0.034, χ (2)-test; odds ratio=1.46).