PT  - JOURNAL ARTICLE
AU  - Jorge L Del-Aguila
AU  - Benjamin Saef
AU  - Kathleen Black
AU  - Maria Victoria Fernandez
AU  - John Budde
AU  - Laura Ibanez
AU  - Manav Kapoor
AU  - Giuseppe Tosto
AU  - Richard P Mayeux
AU  - David M Holtzman
AU  - Anne M. Fagan
AU  - John C Morris
AU  - Randall J. Bateman
AU  - Alison Goate
AU  - the Dominantly Inherited Alzheimer Network (DIAN), Disease Neuroimaging Initiative (ADNI)
AU  - the NIA-LOAD family study
AU  - Carlos Cruchaga
AU  - Oscar Harari
TI  - Polygenic Risk Score of Sporadic late Onset Alzheimer Disease Reveals a Shared Architecture with the Familial and Early Onset Forms
AID  - 10.1101/165209
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 165209
4099  - http://biorxiv.org/content/early/2017/07/19/165209.short
4100  - http://biorxiv.org/content/early/2017/07/19/165209.full
AB  - 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-Aβ42 on 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.