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

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

Tesi, N. (TU Delft Pattern Recognition and Bioinformatics; Vrije Universiteit Amsterdam)
Stringa, N. (Amsterdam UMC)
Hadjigeorgiou, Georgios (University of Cyprus)
Hulsman, M. (Vrije Universiteit Amsterdam)
van Schoor, Natasja M. (Amsterdam UMC)
Ruiz, A. (Universitat Internacional de Catalunya)
Jansen, Iris E. (Vrije Universiteit Amsterdam)
Holstege, H. (Vrije Universiteit Amsterdam)
van der Lee, S.J. (Vrije Universiteit Amsterdam)

2021

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.

http://resolver.tudelft.nl/uuid:4c240257-f29e-419a-aa0b-9f4e9f47d895

https://doi.org/10.1038/s41467-021-22491-8

2041-1723

Nature Communications, 12 (1)

The original version of this Article omitted from the author list the 212th author Patrizia Mecocci, who is from the Institute of Gerontology and Geriatrics, Department of Medicine, University of Perugia, Perugia, Italy. Consequently, the “Sample Contribution” section of Author Contributions was updated to add “P.M” between “P.D.” and “R.C.”. Additionally, the original version of this Article contained the incorrect affiliation for author Patrick Gavin Kehoe, which incorrectly read “German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany”. The correct version replaces this affiliation with “Bristol Medical School (THS), University of Bristol, Southmead Hospital, Bristol, UK”. This has been corrected in both the PDF and HTML versions of the Article. DOI: https://doi.org/10.1038/s41467-023-36192-x Author notes These authors contributed equally: Itziar de Rojas, Sonia Moreno-Grau, Niccolo Tesi, Benjamin Grenier-Boley, Victor Andrade, Iris E. Jansen. These authors jointly supervised this work: Jordi Clarimón, Mercè Boada, Wiesje M. van der Flier, Alfredo Ramirez, Jean-Charles Lambert, Sven J. van der Lee, Agustín Ruiz.

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© 2021 N. Tesi, N. Stringa, Georgios Hadjigeorgiou, M. Hulsman, Natasja M. van Schoor, A. Ruiz, Iris E. Jansen, H. Holstege, S.J. van der Lee, More Authors