1. Polygenic Risk Score of Sporadic late Onset Alzheimer Disease Reveals a Shared Architecture with the Familial and Early Onset Forms
- Author
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Richard Mayeux, Kathleen Black, Manav Kapoor, John P. Budde, John C. Morris, Laura Ibanez, Giuseppe Tosto, Alison Goate, David M. Holtzman, Anne M. Fagan, Benjamin Saef, Oscar Harari, Jorge Del aguila, Randall J. Bateman, Carlos Cruchaga, and Maria Victoria Fernandez
- Subjects
Genetics ,0303 health sciences ,business.industry ,Late Onset Alzheimer Disease ,Familial clustering ,Disease ,medicine.disease ,Genetic architecture ,03 medical and health sciences ,0302 clinical medicine ,Medicine ,Polygenic risk score ,Alzheimer's disease ,business ,030217 neurology & neurosurgery ,030304 developmental biology ,Early onset - Abstract
Objective:To determine whether the genetic architecture of sporadic late-onset Alzheimer’s Disease (sLOAD) has an effect on familial late-onset AD (fLOAD), sporadic early-onset (sEOAD) and autosomal dominant early-onset (eADAD).Methods:Polygenic risk scores (PRS) were constructed using previously identified 21 genome-wide significant loci for LOAD risk.Results:We found that there is an overlap in the genetic architecture among sEOAD, fLOAD, and sLOAD. sEOAD showed the highest odds for the PRS (OR=2.27; p=1.29×10-7), followed by fLOAD (OR=1.75; p=1.12×10-7) and sLOAD (OR=1.40; p=1.21×10-3). PRS is associated with cerebrospinal fluid ptau181-Aβ42on eADAD.Conclusion:Our analysis confirms that the genetic factors identified for sLOAD also modulate risk in fLOAD and sEOAD cohorts. Furthermore, our results suggest that the burden of these risk variants is associated with familial clustering and earlier-onset of AD. Although these variants are not associated with risk in the eADAD, they may be modulating age at onset.
- Published
- 2017