Job-related exhaustion risk variant in UST is associated with dementia and DNA methylation

Autor: Sonja Sulkava, Jari Haukka, Karri Kaivola, Fatma Doagu, Alexandra Lahtinen, Katri Kantojärvi, Kalle Pärn, Priit Palta, Liisa Myllykangas, Raimo Sulkava, Tiina Laatikainen, Pentti J. Tienari, Tiina Paunio
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Scientific Reports, Vol 14, Iss 1, Pp 1-13 (2024)
Druh dokumentu: article
ISSN: 2045-2322
DOI: 10.1038/s41598-024-62600-3
Popis: Abstract Previous genome-wide association and replication study for job-related exhaustion indicated a risk variant, rs13219957 in the UST gene. Epidemiological studies suggest connection of stress-related conditions and dementia risk. Therefore, we first studied association of rs13219957 and register-based incident dementia using survival models in the Finnish National FINRISK study surveys (N = 26,693). The AA genotype of rs13219957 was significantly associated with 40% increased risk of all-cause dementia. Then we analysed the UST locus association with brain pathology in the Vantaa 85+ cohort and found association with tau pathology (Braak stage) but not with amyloid pathology. Finally, in the functional analyses, rs13219957 showed a highly significant association with two DNA methylation sites of UST, and UST expression. Thus, the results suggest a common risk variant for a stress-related condition and dementia. Mechanisms to mediate the connection may include differential DNA methylation and transcriptional regulation of UST.
Databáze: Directory of Open Access Journals
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