Consensus meta-analysis of genome-wide association studies for Alzheimer’s disease and related dementias

@article{biobank2026consensus,
  title = {{Consensus meta-analysis of genome-wide association studies for Alzheimer’s disease and related dementias}},
  author = {EADB (Alzheimer Disease European DNA biobank) and Céline Bellenguez and Atahualpa Castillo-Morales and Najaf Amin and Sven J. van der Lee and Manon Muntaner and Kayenat Parveen and Fahri Küçükali and Benjamin Grenier‐Boley and Sami Heikkinen and Itziar de Rojas and Maria Carolina Dalmasso and Luca Kleineidam and Oliver Peters and Anja Schneider and Martin Dichgans and Dan Rujescu and Norbert Scherbaum and Jürgen Deckert and Steffi Riedel-Heller and Lucrezia Hausner and Laura Molina‐Porcel and Emrah Düzel and Timo Grimmer and Jens Wiltfang and Stefanie Heilmann‐Heimbach and Susanne Moebus and Matthias Schmid and Thomas Tegos and Nikolaos Scarmeas and Oriol Dols‐Icardo and Fermín Moreno and Jordi Pérez‐Tur and María José Bullido and Pau Pástor and Raquel Sánchez‐Valle and Victoria Álvarez and Merçé Boada and Pablo García‐González and Raquel Puerta and Pablo Mir and Luis M. Real and Gerard Piñol‐Ripoll and José María García‐Alberca and Eloy Rodríguez‐Rodríguez and Hilkka S. Soininen and Alexandre de Mendonça and Shima Mehrabian and Jakub Hort and Martin Vyhnálek and Nicolai Sandau and Jiao Luo and Jesper Qvist Thomassen and Yolande A.L. Pijnenburg and Wiesje M. van der Flier and Harro Seelaar and Inez H.G.B. Ramakers and Janne M. Papma and Marc Hulsman and Gert-Jan Biessels},
  journal = {Nature Genetics},
  year = {2026},
  month = jun,
  doi = {10.1038/s41588-026-02583-1},
  url = {https://doi.org/10.1038/s41588-026-02583-1},
  note = {CC BY},
}

TY  - JOUR
TI  - Consensus meta-analysis of genome-wide association studies for Alzheimer’s disease and related dementias
AU  - EADB (Alzheimer Disease European DNA biobank)
AU  - Céline Bellenguez
AU  - Atahualpa Castillo-Morales
AU  - Najaf Amin
AU  - Sven J. van der Lee
AU  - Manon Muntaner
AU  - Kayenat Parveen
AU  - Fahri Küçükali
AU  - Benjamin Grenier‐Boley
AU  - Sami Heikkinen
AU  - Itziar de Rojas
AU  - Maria Carolina Dalmasso
AU  - Luca Kleineidam
AU  - Oliver Peters
AU  - Anja Schneider
AU  - Martin Dichgans
AU  - Dan Rujescu
AU  - Norbert Scherbaum
AU  - Jürgen Deckert
AU  - Steffi Riedel-Heller
AU  - Lucrezia Hausner
AU  - Laura Molina‐Porcel
AU  - Emrah Düzel
AU  - Timo Grimmer
AU  - Jens Wiltfang
AU  - Stefanie Heilmann‐Heimbach
AU  - Susanne Moebus
AU  - Matthias Schmid
AU  - Thomas Tegos
AU  - Nikolaos Scarmeas
AU  - Oriol Dols‐Icardo
AU  - Fermín Moreno
AU  - Jordi Pérez‐Tur
AU  - María José Bullido
AU  - Pau Pástor
AU  - Raquel Sánchez‐Valle
AU  - Victoria Álvarez
AU  - Merçé Boada
AU  - Pablo García‐González
AU  - Raquel Puerta
AU  - Pablo Mir
AU  - Luis M. Real
AU  - Gerard Piñol‐Ripoll
AU  - José María García‐Alberca
AU  - Eloy Rodríguez‐Rodríguez
AU  - Hilkka S. Soininen
AU  - Alexandre de Mendonça
AU  - Shima Mehrabian
AU  - Jakub Hort
AU  - Martin Vyhnálek
AU  - Nicolai Sandau
AU  - Jiao Luo
AU  - Jesper Qvist Thomassen
AU  - Yolande A.L. Pijnenburg
AU  - Wiesje M. van der Flier
AU  - Harro Seelaar
AU  - Inez H.G.B. Ramakers
AU  - Janne M. Papma
AU  - Marc Hulsman
AU  - Gert-Jan Biessels
PY  - 2026
DA  - 2026/06/01
JO  - Nature Genetics
DO  - 10.1038/s41588-026-02583-1
UR  - https://doi.org/10.1038/s41588-026-02583-1
AB  - To better characterize the genetic architecture underlying Alzheimer's disease (AD) and related dementias (ADRD), we performed a meta-analysis of European-ancestry genome-wide association studies in 128,681 cases or proxy cases of ADRD and 849,833 (proxy) controls. We identified 91 genetic loci associated with ADRD risk, of which 16 are new and 56 are specifically detected in clinically diagnosed AD cases. We also provide a list of 18 loci (15 new) requiring further external validation. A polygenic score combining the effects of ADRD loci other than APOE was primarily associated with AD rather than non-AD pathology. Individuals in the tenth decile of the score exhibited a twofold increased risk of presenting with Braak neurofibrillary tangles stage of >4 and moderate-to-severe neuritic amyloid plaque pathology at death compared to individuals in the median score group. In conclusion, our study validated a large number of loci associated with the risk of clinically diagnosed AD, while further investigations are required to confirm the impact of the other loci on AD clinical diagnosis and of each locus on AD pathology.
SN  - 1061-4036
SN  - 1546-1718
ER  -