Common variants in Alzheimer's disease and risk stratification by polygenic risk scores

EADB contributors, GR@ACE study group, DEGESCO consortium, IGAP (ADGC, CHARGE, EADI, GERAD), PGC-ALZ consortia, Itziar de Rojas, Sonia Moreno-Grau, Niccolo Tesi, Benjamin Grenier-Boley, Victor Andrade, Iris E. Jansen, Nancy L. Pedersen, Najada Stringa, Anna Zettergren, Isabel Hernández, Laura Montrreal, Carmen Antúnez, Anna Antonell, Rick M. Tankard, Joshua C. BisRebecca Sims, Céline Bellenguez, Inés Quintela, Antonio González-Perez, Miguel Calero, Emilio Franco-Macías, Juan Macías, Rafael Blesa, Laura Cervera-Carles, Manuel Menéndez-González, Ana Frank-García, Jose Luís Royo, Fermin Moreno, Barbara Borroni, Beatrice Arosio, Benedetta Nacmias, Chiara Fenoglio, Daniela Galimberti, Davide Seripa, Elio Scarpini, Evelyn Ferri, Fabrizio Tagliavini, Giacomina Rossi, Gianfranco Spalletta, Giorgio Giaccone, Giuliano Binetti, Luisa Benussi, Marina Arcaro, Nerisa Banaj, Paola Bossù, Paolo Dionigi Rossi, Roberta Ghidoni, Sandro Sorbi, Silvia Fostinelli, Simona Ciccone

Research output: Contribution to journalArticlepeer-review


Genetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer's disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer's disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer's disease.

Original languageEnglish
Pages (from-to)3417
Number of pages1
JournalNature Communications
Issue number1
Publication statusPublished - Jun 7 2021

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)


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