FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3189793883> ?p ?o ?g. }

• W3189793883 abstract "Abstract Although genome-wide association studies (GWAS) have identified thousands of disease-associated common SNPs, these SNPs generally do not implicate the underlying target genes, as most disease SNPs are regulatory. Many SNP-to-gene (S2G) linking strategies have been developed to link regulatory SNPs to the genes that they regulate in cis , but it is unclear how these strategies should be applied in the context of interpreting common disease risk variants. We developed a framework for evaluating and combining different S2G strategies to optimize their informativeness for common disease risk, leveraging polygenic analyses of disease heritability to define and estimate their precision and recall . We applied our framework to GWAS summary statistics for 63 diseases and complex traits (average N =314K), evaluating 50 S2G strategies. Our optimal combined S2G strategy (cS2G) included 7 constituent S2G strategies (Exon, Promoter, 2 fine-mapped cis -eQTL strategies, EpiMap enhancer-gene linking, Activity-By-Contact (ABC), and Cicero), and achieved a precision of 0.75 and a recall of 0.33, more than doubling the precision and/or recall of any individual strategy; this implies that 33% of SNP-heritability can be linked to causal genes with 75% confidence. We applied cS2G to fine-mapping results for 49 UK Biobank diseases/traits to predict 7,111 causal SNP-gene-disease triplets (with S2G-derived functional interpretation) with high confidence. Finally, we applied cS2G to genome-wide fine-mapping results for these traits (not restricted to GWAS loci) to rank genes by the heritability linked to each gene, providing an empirical assessment of disease omnigenicity; averaging across traits, we determined that the top 200 (1%) of ranked genes explained roughly half of the heritability linked to all genes. Our results highlight the benefits of our cS2G strategy in providing functional interpretation of GWAS findings; we anticipate that precision and recall will increase further under our framework as improved functional assays lead to improved S2G strategies." @default.
• W3189793883 created "2021-08-16" @default.
• W3189793883 creator A5016230870 @default.
• W3189793883 creator A5028616817 @default.
• W3189793883 creator A5030938002 @default.
• W3189793883 creator A5034206272 @default.
• W3189793883 creator A5034446085 @default.
• W3189793883 creator A5042815092 @default.
• W3189793883 creator A5046661602 @default.
• W3189793883 creator A5057203825 @default.
• W3189793883 creator A5057630970 @default.
• W3189793883 creator A5057743688 @default.
• W3189793883 creator A5062800512 @default.
• W3189793883 creator A5066797582 @default.
• W3189793883 creator A5079614072 @default.
• W3189793883 date "2021-08-05" @default.
• W3189793883 modified "2023-09-26" @default.
• W3189793883 title "Combining SNP-to-gene linking strategies to pinpoint disease genes and assess disease omnigenicity" @default.
• W3189793883 cites W1636205509 @default.
• W3189793883 cites W1844405070 @default.
• W3189793883 cites W1971751459 @default.
• W3189793883 cites W1988331425 @default.
• W3189793883 cites W2024439539 @default.
• W3189793883 cites W2038049117 @default.
• W3189793883 cites W2051314902 @default.
• W3189793883 cites W2056198580 @default.
• W3189793883 cites W2060270800 @default.
• W3189793883 cites W2073836327 @default.
• W3189793883 cites W2076154138 @default.
• W3189793883 cites W2078059415 @default.
• W3189793883 cites W2104549677 @default.
• W3189793883 cites W2110676385 @default.
• W3189793883 cites W2117446594 @default.
• W3189793883 cites W2117792884 @default.
• W3189793883 cites W2118198468 @default.
• W3189793883 cites W2127751349 @default.
• W3189793883 cites W2128016314 @default.
• W3189793883 cites W2133009026 @default.
• W3189793883 cites W2135735996 @default.
• W3189793883 cites W2135993011 @default.
• W3189793883 cites W2145191876 @default.
• W3189793883 cites W2146774792 @default.
• W3189793883 cites W2148201806 @default.
• W3189793883 cites W2153118028 @default.
• W3189793883 cites W2173732482 @default.
• W3189793883 cites W2264585211 @default.
• W3189793883 cites W2288649857 @default.
• W3189793883 cites W2297334215 @default.
• W3189793883 cites W2553838260 @default.
• W3189793883 cites W2555614465 @default.
• W3189793883 cites W2573291923 @default.
• W3189793883 cites W2590321928 @default.
• W3189793883 cites W2606675097 @default.
• W3189793883 cites W2626606138 @default.
• W3189793883 cites W2725988230 @default.
• W3189793883 cites W2738082385 @default.
• W3189793883 cites W2765253743 @default.
• W3189793883 cites W2766412303 @default.
• W3189793883 cites W2804434811 @default.
• W3189793883 cites W2806225217 @default.
• W3189793883 cites W2808363286 @default.
• W3189793883 cites W2809388509 @default.
• W3189793883 cites W2811205482 @default.
• W3189793883 cites W2887694579 @default.
• W3189793883 cites W2895486342 @default.
• W3189793883 cites W2896352133 @default.
• W3189793883 cites W2897334647 @default.
• W3189793883 cites W2898598946 @default.
• W3189793883 cites W2901303766 @default.
• W3189793883 cites W2906884244 @default.
• W3189793883 cites W2934861239 @default.
• W3189793883 cites W2943309532 @default.
• W3189793883 cites W2952835495 @default.
• W3189793883 cites W2952882474 @default.
• W3189793883 cites W2953357410 @default.
• W3189793883 cites W2955994579 @default.
• W3189793883 cites W2957675127 @default.
• W3189793883 cites W2963404097 @default.
• W3189793883 cites W2965985232 @default.
• W3189793883 cites W2966010373 @default.
• W3189793883 cites W2979683718 @default.
• W3189793883 cites W2991283206 @default.
• W3189793883 cites W2994150660 @default.
• W3189793883 cites W2999574254 @default.
• W3189793883 cites W2999883126 @default.
• W3189793883 cites W3002247544 @default.
• W3189793883 cites W3004748148 @default.
• W3189793883 cites W3025047014 @default.
• W3189793883 cites W3029661147 @default.
• W3189793883 cites W3042068575 @default.
• W3189793883 cites W3042292144 @default.
• W3189793883 cites W3083216853 @default.
• W3189793883 cites W3083925241 @default.
• W3189793883 cites W3094550675 @default.
• W3189793883 cites W3102939328 @default.
• W3189793883 cites W3127556601 @default.
• W3189793883 cites W3133859624 @default.
• W3189793883 cites W3138461147 @default.
• W3189793883 cites W3149376923 @default.
• W3189793883 cites W3151678771 @default.

• next