Abstract
Brain arteriolosclerosis (B-ASC) is characterized by pathologically altered brain parenchymal arterioles. B-ASC is associated with cognitive impairment and increased likelihood of clinical dementia. To date, no study has been conducted on genome-wide genetic risk of autopsy-proven B-ASC. We performed a genome-wide association study (GWAS) of the B-ASC phenotype using multiple independent aged neuropathologic cohorts. Included in the study were participants with B-ASC autopsy and genotype data available from the NACC, ROSMAP, ADNI, and ACT data sets. Initial Stage 1 GWAS (n = 3382) and Stage 2 mega-analysis (n = 4569) were performed using data from the two largest cohorts (NACC and ROSMAP). Replication of top variants and additional Stage 3 mega-analysis were performed incorporating two smaller cohorts (ADNI and ACT). Lead variants in the top two loci in the Stage 2 mega-analysis (rs7902929, p = (Formula presented.) ; rs2603462, p = (Formula presented.)) were significant in the ADNI cohort (rs7902929, p = (Formula presented.) ; rs2603462, p = (Formula presented.)). The rs2603462 lead variant colocalized with ELOVL4 expression in the cerebellum (posterior probability = 90.1%). Suggestive associations were also found near SORCS1 and SORCS3. We thus identified putative loci associated with B-ASC risk, but additional replication is needed.
Original language | English |
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Pages (from-to) | 1437-1450 |
Number of pages | 14 |
Journal | Journal of Cerebral Blood Flow and Metabolism |
Volume | 42 |
Issue number | 8 |
DOIs | |
State | Published - Aug 2022 |
Bibliographical note
Publisher Copyright:© The Author(s) 2022.
Keywords
- SVD
- VCID
- aging
- arteriosclerosis
- dementia
- neuropathology
ASJC Scopus subject areas
- Neurology
- Clinical Neurology
- Cardiology and Cardiovascular Medicine