PLoS genetics · 2016

Rare Functional Variant in TM2D3 is Associated with Late-Onset Alzheimer's Disease.

СтатьяНазвание и аннотация: Перевод пока не подготовлен

Обработка статьи · этапы, ошибки и управление

Загрузка состояния…

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.

Jakobsdottir Johanna, van der Lee Sven J, Bis Joshua C, Chouraki Vincent, Li-Kroeger David, Yamamoto Shinya, Grove Megan L, Naj Adam, Vronskaya Maria, Salazar Jose L, DeStefano Anita L, Brody Jennifer A, Smith Albert V, Amin Najaf, Sims Rebecca, Ibrahim-Verbaas Carla A, Choi Seung-Hoan, Satizabal Claudia L, Lopez Oscar L, Beiser Alexa, Ikram M Arfan, Garcia Melissa E, Hayward Caroline, Varga Tibor V, Ripatti Samuli, Franks Paul W, Hallmans Göran, Rolandsson Olov, Jansson Jan-Håkon, Porteous David J, Salomaa Veikko, Eiriksdottir Gudny, Rice Kenneth M, Bellen Hugo J, Levy Daniel, Uitterlinden Andre G, Emilsson Valur, Rotter Jerome I, Aspelund Thor, Cohorts for Heart and Aging Research in Genomic Epidemiology consortium, Alzheimer’s Disease Genetic Consortium, Genetic and Environmental Risk in Alzheimer’s Disease consortium, O'Donnell Christopher J, Fitzpatrick Annette L, Launer Lenore J, Hofman Albert, Wang Li-San, Williams Julie, Schellenberg Gerard D, Boerwinkle Eric, Psaty Bruce M, Seshadri Sudha, Shulman Joshua M, Gudnason Vilmundur, van Duijn Cornelia M

Аннотация

We performed an exome-wide association analysis in 1393 late-onset Alzheimer's disease (LOAD) cases and 8141 controls from the CHARGE consortium. We found that a rare variant (P155L) in TM2D3 was enriched in Icelanders (~0.5% versus <0.05% in other European populations). In 433 LOAD cases and 3903 controls from the Icelandic AGES sub-study, P155L was associated with increased risk and earlier onset of LOAD [odds ratio (95% CI) = 7.5 (3.5-15.9), p = 6.6x10-9]. Mutation in the Drosophila TM2D3 homolog, almondex, causes a phenotype similar to loss of Notch/Presenilin signaling. Human TM2D3 is capable of rescuing these phenotypes, but this activity is abolished by P155L, establishing it as a functionally damaging allele. Our results establish a rare TM2D3 variant in association with LOAD susceptibility, and together with prior work suggests possible links to the β-amyloid cascade.

Rare Functional Variant in TM2D3 is Associated with Late-Onset Alzheimer's Disease.

Ошибки и ограничения

Аннотация

Предметные рубрики MeSH