Genome-wide association scan identifies new variants associated with a cognitive predictor of dyslexia.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
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.
Gialluisi Alessandro, Andlauer Till F M, Mirza-Schreiber Nazanin, Moll Kristina, Becker Jessica, Hoffmann Per, Ludwig Kerstin U, Czamara Darina, St Pourcain Beate, Brandler William, Honbolygó Ferenc, Tóth Dénes, Csépe Valéria, Huguet Guillaume, Morris Andrew P, Hulslander Jacqueline, Willcutt Erik G, DeFries John C, Olson Richard K, Smith Shelley D, Pennington Bruce F, Vaessen Anniek, Maurer Urs, Lyytinen Heikki, Peyrard-Janvid Myriam, Leppänen Paavo H T, Brandeis Daniel, Bonte Milene, Stein John F, Talcott Joel B, Fauchereau Fabien, Wilcke Arndt, Francks Clyde, Bourgeron Thomas, Monaco Anthony P, Ramus Franck, Landerl Karin, Kere Juha, Scerri Thomas S, Paracchini Silvia, Fisher Simon E, Schumacher Johannes, Nöthen Markus M, Müller-Myhsok Bertram, Schulte-Körne Gerd
Аннотация
Developmental dyslexia (DD) is one of the most prevalent learning disorders, with high impact on school and psychosocial development and high comorbidity with conditions like attention-deficit hyperactivity disorder (ADHD), depression, and anxiety. DD is characterized by deficits in different cognitive skills, including word reading, spelling, rapid naming, and phonology. To investigate the genetic basis of DD, we conducted a genome-wide association study (GWAS) of these skills within one of the largest studies available, including nine cohorts of reading-impaired and typically developing children of European ancestry (N = 2562-3468). We observed a genome-wide significant effect (p < 1 × 10-8) on rapid automatized naming of letters (RANlet) for variants on 18q12.2, within MIR924HG (micro-RNA 924 host gene; rs17663182 p = 4.73 × 10-9), and a suggestive association on 8q12.3 within NKAIN3 (encoding a cation transporter; rs16928927, p = 2.25 × 10-8). rs17663182 (18q12.2) also showed genome-wide significant multivariate associations with RAN measures (p = 1.15 × 10-8) and with all the cognitive traits tested (p = 3.07 × 10-8), suggesting (relational) pleiotropic effects of this variant. A polygenic risk score (PRS) analysis revealed significant genetic overlaps of some of the DD-related traits with educational attainment (EDUyears) and ADHD. Reading and spelling abilities were positively associated with EDUyears (p ~ [10-5-10-7]) and negatively associated with ADHD PRS (p ~ [10-8-10-17]). This corroborates a long-standing hypothesis on the partly shared genetic etiology of DD and ADHD, at the genome-wide level. Our findings suggest new candidate DD susceptibility genes and provide new insights into the genetics of dyslexia and its comorbities.