Genetic associations with age at dementia onset in the PSEN1 E280A Colombian kindred.
Обработка статьи · этапы, ошибки и управление
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Cochran Jesse Nicholas, Acosta-Uribe Juliana, Esposito Bianca T, Madrigal Lucia, Aguillón David, Giraldo Margarita M, Taylor Jared W, Bradley Joseph, Fulton-Howard Brian, Andrews Shea J, Acosta-Baena Natalia, Alzate Diana, Garcia Gloria P, Piedrahita Francisco, Lopez Hugo E, Anderson Ashlyn G, Rodriguez-Nunez Ivan, Roberts Kevin, Dominantly Inherited Alzheimer Network, Absher Devin, Myers Richard M, Beecham Gary W, Reitz Christiane, Rizzardi Lindsay F, Fernandez Maria Victoria, Goate Alison M, Cruchaga Carlos, Renton Alan E, Lopera Francisco, Kosik Kenneth S
Аннотация
METHODS: A genetic association study was conducted to examine ADAD AAO in 340 individuals with the PSEN1 E280A mutation via TOPMed array imputation. Replication was assessed in two ADAD cohorts, one sporadic early-onset AD study and four late-onset AD studies.
RESULTS: 13 variants had p<1×10-7 or p<1×10-5 with replication including three independent loci with candidate associations with clusterin including near CLU. Other suggestive associations were identified in or near HS3ST1, HSPG2, ACE, LRP1B, TSPAN10, and TSPAN14.
DISCUSSION: Variants with suggestive associations with AAO were associated with biological processes including clusterin, heparin sulfate, and amyloid processing. The detection of these effects in the presence of a strong mutation for ADAD reinforces their potentially impactful role.