FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3197499265> ?p ?o ?g. }

• W3197499265 endingPage "422" @default.
• W3197499265 startingPage "410" @default.
• W3197499265 abstract "Genome-wide association studies (GWAS) have identified ~20 genetic susceptibility loci for esophageal adenocarcinoma (EAC), and its precursor, Barrett's esophagus (BE). Despite such advances, functional/causal variants and gene targets at these loci remain undefined, hindering clinical translation. A key challenge is that most causal variants map to non-coding regulatory regions such as enhancers, and typically, numerous potential candidate variants at GWAS loci require testing. We developed a systematic informatics pipeline for prioritizing candidate functional variants via integrative functional potential scores (FPS) consolidated from multi-omics annotations, and used this pipeline to identify two high-scoring variants for experimental interrogation: chr9q22.32/rs11789015 and chr19p13.11/rs10423674. Minimal candidate enhancer regions spanning these variants were evaluated using luciferase reporter assays in two EAC cell lines. One of the two variants tested (rs10423674) exhibited allele-specific enhancer activity. CRISPR-mediated deletion of the putative enhancer region in EAC cell lines correlated with reduced expression of two genes-CREB-regulated transcription coactivator 1 (CRTC1) and Cartilage oligomeric matrix protein (COMP); expression of five other genes remained unchanged (CRLF1, KLHL26, TMEM59L, UBA52, RFXANK). Expression quantitative trait locus mapping indicated that rs10423674 genotype correlated with CRTC1 and COMP expression in normal esophagus. This study represents the first experimental effort to bridge GWAS associations to biology in BE/EAC and supports the utility of FPS to guide variant prioritization. Our findings reveal a functional variant and candidate risk enhancer at chr19p13.11 and implicate CRTC1 and COMP as putative gene targets, suggesting that altered expression of these genes may underlie the BE/EAC risk association." @default.
• W3197499265 created "2021-09-13" @default.
• W3197499265 creator A5011306393 @default.
• W3197499265 creator A5013835204 @default.
• W3197499265 creator A5026373258 @default.
• W3197499265 creator A5030872551 @default.
• W3197499265 creator A5032281064 @default.
• W3197499265 creator A5068204742 @default.
• W3197499265 creator A5068325965 @default.
• W3197499265 creator A5084496654 @default.
• W3197499265 date "2021-09-09" @default.
• W3197499265 modified "2023-10-16" @default.
• W3197499265 title "Prioritization and functional analysis of GWAS risk loci for Barrett’s esophagus and esophageal adenocarcinoma" @default.
• W3197499265 cites W1163643844 @default.
• W3197499265 cites W1514032394 @default.
• W3197499265 cites W1915704240 @default.
• W3197499265 cites W1946640880 @default.
• W3197499265 cites W1964963969 @default.
• W3197499265 cites W1968339490 @default.
• W3197499265 cites W1978136073 @default.
• W3197499265 cites W1978403601 @default.
• W3197499265 cites W1978908066 @default.
• W3197499265 cites W2004966039 @default.
• W3197499265 cites W2009661936 @default.
• W3197499265 cites W2013997037 @default.
• W3197499265 cites W2014042333 @default.
• W3197499265 cites W2014656523 @default.
• W3197499265 cites W2030235211 @default.
• W3197499265 cites W2045459421 @default.
• W3197499265 cites W2048143418 @default.
• W3197499265 cites W2049031369 @default.
• W3197499265 cites W2051347917 @default.
• W3197499265 cites W2051435398 @default.
• W3197499265 cites W2060525726 @default.
• W3197499265 cites W2060971625 @default.
• W3197499265 cites W2064550415 @default.
• W3197499265 cites W2071456214 @default.
• W3197499265 cites W2073836327 @default.
• W3197499265 cites W2076154138 @default.
• W3197499265 cites W2078059415 @default.
• W3197499265 cites W2096184363 @default.
• W3197499265 cites W2099154089 @default.
• W3197499265 cites W2101720796 @default.
• W3197499265 cites W2103176059 @default.
• W3197499265 cites W2109984612 @default.
• W3197499265 cites W2113974339 @default.
• W3197499265 cites W2119936758 @default.
• W3197499265 cites W2124142551 @default.
• W3197499265 cites W2127113605 @default.
• W3197499265 cites W2128016314 @default.
• W3197499265 cites W2128758643 @default.
• W3197499265 cites W2129773935 @default.
• W3197499265 cites W2135176038 @default.
• W3197499265 cites W2140102429 @default.
• W3197499265 cites W2145378917 @default.
• W3197499265 cites W2156902902 @default.
• W3197499265 cites W2161218516 @default.
• W3197499265 cites W2166320441 @default.
• W3197499265 cites W2168544170 @default.
• W3197499265 cites W2195359644 @default.
• W3197499265 cites W2221218983 @default.
• W3197499265 cites W2230150749 @default.
• W3197499265 cites W2289678000 @default.
• W3197499265 cites W2314540303 @default.
• W3197499265 cites W2328577203 @default.
• W3197499265 cites W2406216445 @default.
• W3197499265 cites W2413013962 @default.
• W3197499265 cites W2494098402 @default.
• W3197499265 cites W2498345959 @default.
• W3197499265 cites W2567033847 @default.
• W3197499265 cites W2736147572 @default.
• W3197499265 cites W2737970188 @default.
• W3197499265 cites W2752775557 @default.
• W3197499265 cites W2757770824 @default.
• W3197499265 cites W2761527879 @default.
• W3197499265 cites W2762576593 @default.
• W3197499265 cites W2773083334 @default.
• W3197499265 cites W2793146419 @default.
• W3197499265 cites W2891314908 @default.
• W3197499265 cites W2897502144 @default.
• W3197499265 cites W2898215009 @default.
• W3197499265 cites W2902503114 @default.
• W3197499265 cites W2944783947 @default.
• W3197499265 cites W2955994579 @default.
• W3197499265 cites W2974503949 @default.
• W3197499265 cites W2981263336 @default.
• W3197499265 cites W2994813193 @default.
• W3197499265 cites W3004613412 @default.
• W3197499265 cites W3010054644 @default.
• W3197499265 cites W3044915036 @default.
• W3197499265 cites W3046196569 @default.
• W3197499265 cites W3098577552 @default.
• W3197499265 cites W3099179344 @default.
• W3197499265 cites W3108451992 @default.
• W3197499265 cites W3111482730 @default.
• W3197499265 cites W3123446607 @default.
• W3197499265 cites W3133859624 @default.
• W3197499265 cites W4231972486 @default.

• next