RT Journal Article
SR Electronic
T1 GRIPT: A novel case-control analysis method for Mendelian disease gene discovery
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 454975
DO 10.1101/454975
A1 Jun Wang
A1 Li Zhao
A1 Xia Wang
A1 Yong Chen
A1 Mingchu Xu
A1 Zachry T. Soens
A1 Zhongqi Ge
A1 Peter Ronghan Wang
A1 Fei Wang
A1 Rui Chen
YR 2018
UL http://biorxiv.org/content/early/2018/10/29/454975.abstract
AB Despite rapid progress of next-generation sequencing (NGS) technologies, the disease-causing genes underpinning about 50% of Mendelian diseases remain elusive. One main challenge is the high genetic heterogeneity of Mendelian diseases in which similar phenotypes are caused by different genes and each gene only accounts for a small proportion of the patients. To overcome this gap, we developed a novel method, the Gene Ranking, Identification and Prediction Tool (GRIPT), for performing case-control analysis of NGS data. Analyses of simulated and real datasets show that GRIPT is well-powered for disease gene discovery, especially for diseases with high locus heterogeneity.List of abbreviationsAFRAfrican/African AmericanAMRAmericanARAutosomal recessiveADAutosomal dominantCADDCombined Annotation Dependent DepletionCASTCohort Allelic Sums TestCMCCombined Multivariate and CollapsingDANNDeleterious Annotation of genetic variants using Neural NetworksEASEast AsianExACExome Aggregation ConsortiumFINFinnishgnomADgenome Aggregation DatabaseGRIPTGene Ranking, Identification and Prediction ToolGWSLGenome-wide significant levelHGMDHuman Gene Mutation DatabaseKBACKernel-Based Adaptive ClusteringLCALeber’s congenital amaurosisNFENon-Finnish EuropeanNGSNext generation sequencingNSAGNumber of significant autosomal genesOMIMOnline Mendelian Inheritance in ManOTHOtherREVELRare Exome Variant Ensemble LearnerRPRetinitis pigmentosaSASSouth AsianSKATSequence Kernel Association TestVAASTVariant Annotation, Analysis and Search ToolVCFVariant Call FormatWESWhole exome sequencingWGSWhole genome sequencingWRSTWilcox rank sum test