Investigation Of Transcriptional Regulation At The Alzheimer’s Disease Risk Loci. (S28.006)

• DOI: 10.1212/wnl.82.10_supplement.s28.006
• Publication Date: 2023-12-07T11:45:25Z
• Authors: Michaela Kachadoo...; Mariet Allen; Aditya Karhade; Lester Manly; Fanggeng Zou; High Seng Chai; Curtis Younkin; Julia Crook; Vernon Pankratz; Minerva Carrasquillo; Asha Nair; Sumit Middha; Sooraj Maharjan; Thuy Nguyen; Li Ma; Kimberly Malphrus; Sarah Lincoln; Gina Bisceglio; Christopher Kolbert; Jin Jen; Ronald Petersen; Neill Graff-Radford; Steven Younkin; Dennis Dickson; Nilufer Taner

OBJECTIVE:To investigate transcriptional regulation of late-onset Alzheimer’s disease (LOAD) GWAS risk loci genes in the human brain. BACKGROUND:We previously identified genetic associations brain levels at LOAD ABCA7 , BIN1, CLU, CR1 and MS4A4A with cisSNPs, including some top AD variants. Recently, 11 additional were through a large meta-analysis multiple GWAS. In this study, our first aim is to association these novel cis SNPs. Our second evaluate potential role alternative splicing gene expression associations. DESIGN/METHODS:We have already obtained measures ~24,000 transcripts two regions (temporal cortex cerebellum) for ~ 200 subjects ~200 other pathologies using Illumina’s WG-DASL assay. SNPs will be analyzed corresponding linear regression adjusting appropriate covariates. To splicing, we use NanoString nCounter™ technology measure all known candidate ~350 RNA samples. RESULTS:We demonstrated utility approach anticipate that there exist genes, which are likewise influenced by We postulate also confer due exons. CONCLUSIONS:Many associate SNPs, This suggests many variants loci. Dissection expected implications understanding pathophysiology. Study Supported by: R01 AG032990, P50 AG016574 Disclosure: Dr. Kachadoorian has nothing disclose. Allen Karhade Zou Chai Younkin Crook Pankratz received research support from Abbott Laboratories, Inc. Carrasquillo Nair Middha Maharjan Nguyen Ma Malphrus Lincoln Bisceglio Kolbert Jen Petersen personal compensation activities Pfizer, Inc., Janssen Alzheimer9s Immunotherapy. royalty payments Oxford University Press. Graff-Radford Codman as member scientific advisory board. an editorial capacity The Neurologist. Janssen, Pfizer Medivation, Forest Laboratories Allon. Dickson Neotope, consultant. Taner