GBA and APOE ε4 associate with sporadic dementia with Lewy bodies in European genome wide association study

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Abstract

Dementia with Lewy Bodies (DLB) is a common neurodegenerative disorder with poor prognosis and mainly unknown pathophysiology. Heritability estimates exceed 30% but few genetic risk variants have been identified. Here we investigated common genetic variants associated with DLB in a large European multisite sample. We performed a genome wide association study in Norwegian and European cohorts of 720 DLB cases and 6490 controls and included 19 top-associated single-nucleotide polymorphisms in an additional cohort of 108 DLB cases and 75545 controls from Iceland. Overall the study included 828 DLB cases and 82035 controls. Variants in the ASH1L/GBA (Chr1q22) and APOE ε4 (Chr19) loci were associated with DLB surpassing the genome-wide significance threshold (p < 5 × 10 −8 ). One additional genetic locus previously linked to psychosis in Alzheimer’s disease, ZFPM1 (Chr16q24.2), showed suggestive association with DLB at p-value < 1 × 10 −6 . We report two susceptibility loci for DLB at genome-wide significance, providing insight into etiological factors. These findings highlight the complex relationship between the genetic architecture of DLB and other neurodegenerative disorders.

Detaljer

Författare
  • Arvid Rongve
  • Aree Witoelar
  • Agustín Ruiz
  • Lavinia Athanasiu
  • Carla Abdelnour
  • Jordi Clarimon
  • Stefanie Heilmann-Heimbach
  • Isabel Hernández
  • Sonia Moreno-Grau
  • Itziar de Rojas
  • Estrella Morenas-Rodríguez
  • Tormod Fladby
  • Sigrid B. Sando
  • Geir Bråthen
  • Frédéric Blanc
  • Olivier Bousiges
  • Afina W. Lemstra
  • Inger van Steenoven
  • Ina S. Almdahl
  • Lene Pålhaugen
  • Jon A. Eriksen
  • Srdjan Djurovic
  • Eystein Stordal
  • Ingvild Saltvedt
  • Ingun D. Ulstein
  • Francesco Bettella
  • Rahul S. Desikan
  • Ane Victoria Idland
  • Mathias Toft
  • Lasse Pihlstrøm
  • Jon Snaedal
  • Lluís Tárraga
  • Mercè Boada
  • Alberto Lleó
  • Hreinn Stefánsson
  • Kári Stefánsson
  • Alfredo Ramírez
  • Dag Aarsland
  • Ole A. Andreassen
Enheter & grupper
Externa organisationer
  • Haugesund Hospital
  • University of Bergen
  • Oslo university hospital
  • University of Oslo
  • International University of Catalonia
  • Autonomous University of Barcelona
  • CIBER Enfermedades Neurodegenerativas (CIBERNED)
  • University of Bonn
  • Akershus University Hospital
  • Norwegian University of Science and Technology
  • St. Olav’s University Hospital
  • Institut de Biologie Moléculaire et Cellulaire Immunopathologie et Chimie Thérapeutique
  • University of Strasbourg
  • VU University Medical Center
  • Namsos Hospital
  • National University Hospital of Iceland
  • deCODE Genetics, Amgen, Inc.
  • University of Cologne
  • King's College London
  • Stavanger University Hospital
  • University of California, San Francisco
  • Skåne University Hospital
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Medicinsk genetik
  • Neurovetenskaper
Originalspråkengelska
Artikelnummer7013
TidskriftScientific Reports
Volym9
Utgivningsnummer1
StatusPublished - 2019 maj 7
PublikationskategoriForskning
Peer review utfördJa