Alzheimer s & DementiaGenetic & Genomic MedicinePeer-reviewed journal article
Local genetic correlation analysis of Alzheimer's disease and stroke implicates PHLPP1 as a shared locus in individuals of African ancestry
Nicholas R. RayiD, Jiji Thulaseedhara KurupiD, Ajneesh KumariD, Farid RajabliiD, Liyong WangiD, Wanying Xu, Fulai JiniD, Elanur YılmaziD, Çağhan KızıliD, Luciana Bertholim NascibeniD, Sofia MouraiD, Aura María RamíreziD, Olusegun BaiyewuiD, Anthony J. GriswoldiD, Motunrayo Mojoyin CokeriD, Kyle M. Scott, Kazeem AkinwandeiD, Larry Deon Adams, Samuel Diala, Patrice G. Whitehead, Jacob L. McCauleyiD, Mayowa OgunronbiiD, Kara L. Hamilton‐NelsoniD, Albertino Damasceno, Andrew F. ZamaniD, , Christiane ReitziD
Abstract
BackgroundNeuropathological studies indicate a strong association between Alzheimers disease (AD) and stroke, yet the molecular mechanisms underlying this association remain unclear. MethodsLocal genetic correlation analysis was conducted with LAVA using the results from genome-wide association studies on AD and stroke in individuals of African ancestry. Enhanced Hi-C Capture Analysis (eHiCA) examined chromatin interactions using iPSC-derived cells from AD brain autopsy samples. ResultsLAVA identified a region shared between AD and stroke on chromosome 18q21.33(rg = .77, P = 2.41x10-6). eHiCA demonstrated that the AD and stroke loci interact with regulatory elements in PHLPP1. Variants at PHLPP1 were also associated with AD in an independent set of individuals of African ancestry (P = 4.56 x 10-5). ConclusionsThis study identified a region on top of PHLPP1 as a locus associated with both AD and stroke. PHLPP1 inhibits protein kinase B, which contributes to both AD and stroke pathophysiology.
- organism: human
- assay: whole-genome sequencing
- research focus: GWAS / association mapping
- approach: statistical model
- Citations
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- FWCI
- 0.00
- Field percentile
- 26th percentile
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