| http://purl.uniprot.org/citations/33798195 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/33798195 | http://www.w3.org/2000/01/rdf-schema#comment | "Transcriptome-wide association studies (TWAS) have been widely used to integrate transcriptomic and genetic data to study complex human diseases. Within a test dataset lacking transcriptomic data, traditional two-stage TWAS methods first impute gene expression by creating a weighted sum that aggregates SNPs with their corresponding cis-eQTL effects on reference transcriptome. Traditional TWAS methods then employ a linear regression model to assess the association between imputed gene expression and test phenotype, thereby assuming the effect of a cis-eQTL SNP on test phenotype is a linear function of the eQTL's estimated effect on reference transcriptome. To increase TWAS robustness to this assumption, we propose a novel Variance-Component TWAS procedure (VC-TWAS) that assumes the effects of cis-eQTL SNPs on phenotype are random (with variance proportional to corresponding reference cis-eQTL effects) rather than fixed. VC-TWAS is applicable to both continuous and dichotomous phenotypes, as well as individual-level and summary-level GWAS data. Using simulated data, we show VC-TWAS is more powerful than traditional TWAS methods based on a two-stage Burden test, especially when eQTL genetic effects on test phenotype are no longer a linear function of their eQTL genetic effects on reference transcriptome. We further applied VC-TWAS to both individual-level (N = ~3.4K) and summary-level (N = ~54K) GWAS data to study Alzheimer's dementia (AD). With the individual-level data, we detected 13 significant risk genes including 6 known GWAS risk genes such as TOMM40 that were missed by traditional TWAS methods. With the summary-level data, we detected 57 significant risk genes considering only cis-SNPs and 71 significant genes considering both cis- and trans-SNPs, which also validated our findings with the individual-level GWAS data. Our VC-TWAS method is implemented in the TIGAR tool for public use."xsd:string |
| http://purl.uniprot.org/citations/33798195 | http://purl.org/dc/terms/identifier | "doi:10.1371/journal.pgen.1009482"xsd:string |
| http://purl.uniprot.org/citations/33798195 | http://purl.uniprot.org/core/author | "Yang J."xsd:string |
| http://purl.uniprot.org/citations/33798195 | http://purl.uniprot.org/core/author | "Tang S."xsd:string |
| http://purl.uniprot.org/citations/33798195 | http://purl.uniprot.org/core/author | "Epstein M.P."xsd:string |
| http://purl.uniprot.org/citations/33798195 | http://purl.uniprot.org/core/author | "De Jager P.L."xsd:string |
| http://purl.uniprot.org/citations/33798195 | http://purl.uniprot.org/core/author | "Bennett D.A."xsd:string |
| http://purl.uniprot.org/citations/33798195 | http://purl.uniprot.org/core/author | "Buchman A.S."xsd:string |
| http://purl.uniprot.org/citations/33798195 | http://purl.uniprot.org/core/date | "2021"xsd:gYear |
| http://purl.uniprot.org/citations/33798195 | http://purl.uniprot.org/core/name | "PLoS Genet"xsd:string |
| http://purl.uniprot.org/citations/33798195 | http://purl.uniprot.org/core/pages | "e1009482"xsd:string |
| http://purl.uniprot.org/citations/33798195 | http://purl.uniprot.org/core/title | "Novel Variance-Component TWAS method for studying complex human diseases with applications to Alzheimer's dementia."xsd:string |
| http://purl.uniprot.org/citations/33798195 | http://purl.uniprot.org/core/volume | "17"xsd:string |
| http://purl.uniprot.org/citations/33798195 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/33798195 |
| http://purl.uniprot.org/citations/33798195 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/33798195 |
| http://purl.uniprot.org/uniprot/#_O96008-mappedCitation-33798195 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/33798195 |
| http://purl.uniprot.org/uniprot/O96008 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/33798195 |