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

EADB, EADI, Bonn, ADGC, CHARGE, FinnGen, GERAD, GR@ACE/DEGESCO, PGC-ALZ and Castillo Morales, Atahualpa 2026. Consensus meta-analysis of genome-wide association studies for Alzheimer’s disease and related dementias. Nature Genetics 58 , pp. 1214-1225. 10.1038/s41588-026-02583-1

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Abstract

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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Schools > Medicine
Additional Information:	For full author list see article webpage https://doi.org/10.1038/s41588-026-02583-1
Publisher:	Nature Research
ISSN:	1061-4036
Date of First Compliant Deposit:	16 June 2026
Date of Acceptance:	25 March 2026
Last Modified:	16 Jun 2026 10:00
URI:	https://orca.cardiff.ac.uk/id/eprint/187577

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