Journal article
Risk prediction of late-onset Alzheimer’s disease implies an oligogenic architecture
Nature Communications, Vol.11(1), Art. 4799
2020
Abstract
Genetic association studies have identified 44 common genome-wide significant risk loci for late-onset Alzheimer’s disease (LOAD). However, LOAD genetic architecture and prediction are unclear. Here we estimate the optimal P-threshold (Poptimal) of a genetic risk score (GRS) for prediction of LOAD in three independent datasets comprising 676 cases and 35,675 family history proxy cases. We show that the discriminative ability of GRS in LOAD prediction is maximised when selecting a small number of SNPs. Both simulation results and direct estimation indicate that the number of causal common SNPs for LOAD may be less than 100, suggesting LOAD is more oligogenic than polygenic. The best GRS explains approximately 75% of SNP-heritability, and individuals in the top decile of GRS have ten-fold increased odds when compared to those in the bottom decile. In addition, 14 variants are identified that contribute to both LOAD risk and age at onset of LOAD.
Details
- Title
- Risk prediction of late-onset Alzheimer’s disease implies an oligogenic architecture
- Authors/Creators
- Q. Zhang (Author/Creator) - The University of QueenslandJ. Sidorenko (Author/Creator) - The University of QueenslandB. Couvy-Duchesne (Author/Creator) - The University of QueenslandR.E. Marioni (Author/Creator) - Edinburgh Cancer ResearchM.J. Wright (Author/Creator) - The University of QueenslandA.M. Goate (Author/Creator) - Icahn School of Medicine at Mount SinaiE. Marcora (Author/Creator) - Icahn School of Medicine at Mount SinaiK-l Huang (Author/Creator) - Icahn School of Medicine at Mount SinaiT. Porter (Author/Creator)S.M. Laws (Author/Creator) - Edith Cowan UniversityP.S. Sachdev (Author/Creator) - UNSW SydneyK.A. Mather (Author/Creator) - Murdoch UniversityN.J. Armstrong (Author/Creator) - UNSW SydneyA. Thalamuthu (Author/Creator) - UNSW SydneyH. Brodaty (Author/Creator) - The University of QueenslandL. Yengo (Author/Creator) - The University of QueenslandJ. Yang (Author/Creator) - The University of QueenslandN.R. Wray (Author/Creator) - The University of QueenslandA.F. McRae (Author/Creator) - The University of QueenslandP.M. Visscher (Author/Creator) - The University of Queensland
- Publication Details
- Nature Communications, Vol.11(1), Art. 4799
- Publisher
- Springer Nature
- Identifiers
- 991005542712507891
- Copyright
- © 2020 Springer Nature Limited
- Murdoch Affiliation
- Information Technology, Mathematics and Statistics
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Domestic collaboration
- International collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.52 Neurodegenerative Diseases
- 1.52.57 Alzheimer's Mechanisms
- Web Of Science research areas
- Genetics & Heredity
- ESI research areas
- Molecular Biology & Genetics