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Title | Genome-wide association study of brain arteriolosclerosis. |
Publication Type | Journal Article |
Year of Publication | 2022 |
Authors | Shade LMp, Katsumata Y, Hohman TJ, Nho K, Saykin AJ, Mukherjee S, Boehme KL, Kauwe JSk, Farrer LA, Schellenberg GD, Haines JL, Mayeux RP, Schneider JA, Nelson PT, Fardo DW |
Journal | J Cereb Blood Flow Metab |
Volume | 42 |
Issue | 8 |
Pagination | 1437-1450 |
Date Published | 08/2022 |
ISSN | 1559-7016 |
Keywords | Aged, Alzheimer Disease, Arteriolosclerosis, Brain, Genome-Wide Association Study, Humans, Polymorphism, Single Nucleotide |
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 ( = 3382) and Stage 2 mega-analysis ( = 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, = ; rs2603462, = ) were significant in the ADNI cohort (rs7902929, = ; rs2603462, ). The rs2603462 lead variant colocalized with expression in the cerebellum (posterior probability = 90.1%). Suggestive associations were also found near and . We thus identified putative loci associated with B-ASC risk, but additional replication is needed. |
DOI | 10.1177/0271678X211066299 |
Alternate Journal | J Cereb Blood Flow Metab |
PubMed ID | 35156446 |
PubMed Central ID | PMC9274864 |
Grant List | P30 AG013854 / AG / NIA NIH HHS / United States R56 AG057191 / AG / NIA NIH HHS / United States U01 AG032984 / AG / NIA NIH HHS / United States TL1 TR000115 / TR / NCATS NIH HHS / United States R01 AG043379 / AG / NIA NIH HHS / United States P30 AG066509 / AG / NIA NIH HHS / United States TL1 TR001997 / TR / NCATS NIH HHS / United States P30 AG010133 / AG / NIA NIH HHS / United States U24 AG021886 / AG / NIA NIH HHS / United States P30 AG062715 / AG / NIA NIH HHS / United States P30 AG072976 / AG / NIA NIH HHS / United States |