Details

Autor(en) / Beteiligte

• Sulkava, Sonja
• Haukka, Jari
• Kaivola, Karri
• Doagu, Fatma
• Lahtinen, Alexandra
• Kantojärvi, Katri
• Pärn, Kalle
• Palta, Priit
• Myllykangas, Liisa
• Sulkava, Raimo
• Laatikainen, Tiina
• Tienari, Pentti J
• Paunio, Tiina

Titel

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

Ist Teil von

• Scientific reports, 2024-06, Vol.14 (1), p.13668-13

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2024

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.