New insights into the genetic etiology of Alzheimer’s disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin…

• MH
  McLean Hospital
• SO
  School of Medicine, Boston University
• UO
  University of Washington
• UD
  Università degli Studi di Cagliari
• DO
  Development of Innovative Strategies for a Transdisciplinary approach to ALZheimer's disease
• UD
  Université de Lille
• IN
  Institut National de la Santé et de la Recherche Médicale

  Award: U1245
• NA
  National and Kapodistrian University of Athens
• DZ
  Deutsches Zentrum für Neurodegenerative Erkrankungen
• UD
  Universitat de Barcelona
• UZ
  Universität zu Köln
• RF
  Rheinische Friedrich-Wilhelms-Universität Bonn
• UD
  Universität Duisburg-Essen
• HU
  Harokopio University
• CD
  Centro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas
• RN
  Région Normandie
• MR
  Medical Research Council

  Awards: MR/L023784/2, MR/N029402/1, MR/L501517/1, MR/R024804/1, MR/L501529/1, MR/L010305/1, MC_PC_17112, MR/K013041/1, MR/L023784/1, MR/T04604X/1
• BA
  Biotechnology and Biological Sciences Research Council

  Award: BB/W008793/1