eQTL Set-Based Association Analysis Identifies Novel Susceptibility Loci for Barrett Esophagus and Esophageal Adenocarcinoma.
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.
Wang Xiaoyu, Gharahkhani Puya, Levine David M, Fitzgerald Rebecca C, Gockel Ines, Corley Douglas A, Risch Harvey A, Bernstein Leslie, Chow Wong-Ho, Onstad Lynn, Shaheen Nicholas J, Lagergren Jesper, Hardie Laura J, Wu Anna H, Pharoah Paul D P, Liu Geoffrey, Anderson Lesley A, Iyer Prasad G, Gammon Marilie D, Caldas Carlos, Ye Weimin, Barr Hugh, Moayyedi Paul, Harrison Rebecca, Watson R G Peter, Attwood Stephen, Chegwidden Laura, Love Sharon B, MacDonald David, deCaestecker John, Prenen Hans, Ott Katja, Moebus Susanne, Venerito Marino, Lang Hauke, Mayershofer Rupert, Knapp Michael, Veits Lothar, Gerges Christian, Weismüller Josef, Reeh Matthias, Nöthen Markus M, Izbicki Jakob R, Manner Hendrik, Neuhaus Horst, Rösch Thomas, Böhmer Anne C, Hölscher Arnulf H, Anders Mario, Pech Oliver, Schumacher Brigitte, Schmidt Claudia, Schmidt Thomas, Noder Tania, Lorenz Dietmar, Vieth Michael, May Andrea, Hess Timo, Kreuser Nicole, Becker Jessica, Ell Christian, Tomlinson Ian, Palles Claire, Jankowski Janusz A, Whiteman David C, MacGregor Stuart, Schumacher Johannes, Vaughan Thomas L, Buas Matthew F, Dai James Y
Аннотация
METHODS: Using genetic data from 4,323 BE and 4,116 EAC patients aggregated by international consortia including the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON), we conducted a comprehensive transcriptome-wide association study (TWAS) for BE/EAC, leveraging Genotype Tissue Expression (GTEx) gene-expression data from six tissue types of plausible relevance to EAC etiology: mucosa and muscularis from the esophagus, gastroesophageal (GE) junction, stomach, whole blood, and visceral adipose. Two analytical approaches were taken: standard TWAS using the predicted gene expression from local expression quantitative trait loci (eQTL), and set-based SKAT association using selected eQTLs that predict the gene expression.
RESULTS: Although the standard approach did not identify significant signals, the eQTL set-based approach identified eight novel associations, three of which were validated in independent external data (eQTL SNP sets for EXOC3, ZNF641, and HSP90AA1).
CONCLUSIONS: This study identified novel genetic susceptibility loci for EAC and BE using an eQTL set-based genetic association approach.
IMPACT: This study expanded the pool of genetic susceptibility loci for EAC and BE, suggesting the potential of the eQTL set-based genetic association approach as an alternative method for TWAS analysis.