Matches in SemOpenAlex for { <https://semopenalex.org/work/W4315703372> ?p ?o ?g. }
Showing items 1 to 74 of
74
with 100 items per page.
- W4315703372 endingPage "e54" @default.
- W4315703372 startingPage "e54" @default.
- W4315703372 abstract "To explore genetic architecture of hypertension and end-organ damages, we performed integrative genomic analyses in both humans and inbred hypertensive rat strains. In humans, noting that hypertension is more prevalent and contributes to the increased risk of stroke in people of East Asian ancestry, we performed a multi-stage GWAS for blood pressure (BP) principally in East Asians and meta-analysis in East Asians and Europeans. We reported 19 new genetic loci and ancestry-specific BP variants, conforming to a common ancestry-specific variant association model. Some of the ancestry-specific association signals are influenced by a selective sweep. These data provide new evidence for the role of common ancestry-specific variants and natural selection in ethnic differences in complex traits such as BP. In rats, we also performed genomic analyses of BP and related phenotypes in spontaneously hypertensive rats (SHR) and their substrain, stroke-prone SHR (SHRSP). By integrating whole-genome sequencing, transcriptome profiling, genome-wide linkage scans (maximum n = 1415) and fine congenic mapping (maximum n = 8704) plus comparative analysis with human, transcriptome-wide association study (TWAS) datasets, we searched causal genes and causal pathways for the tested traits. The overall results validated the polygenic architecture of elevated BP compared with a non-hypertensive control strain, Wistar Kyoto rats (WKY). We identified 26 potential target genes, including rat homologs of human TWAS loci, for the tested traits. In this analysis, we re-discovered 18 genes that had previously been determined to contribute to hypertension or cardiovascular phenotypes. Notably, five of these genes belong to the kallikrein-kinin/renin-angiotensin systems (KKS/RAS), in which the most prominent differential expression between hypertensive and non-hypertensive alleles could be detected in rat Klk1 paralogs. Furthermore, to unravel the mechanisms underlying antihypertensive drug-induced amelioration of end-organ damages, we performed transcriptomic analysis on the heart and the kidney, with administration of antihypertensive drugs to two inbred rat strains (SHRSP and WKY). Noticeable changes of mRNA expression were induced particularly by RAS blockade, for example, for genes in the natriuretic peptide system (Nppb and Corin) in the heart and for those in the KKS/RAS (Ren and rat Klk1 paralogs) and those related to calcium ion binding (Calb1 and Slc8a1) in the kidney. Taken together, we provide genetic epidemiological evidence for ethnic differences in hypertension susceptibility and also in vivo experimental evidence supporting the presence of key disease pathways, such as KKS/RAS, likely across species." @default.
- W4315703372 created "2023-01-12" @default.
- W4315703372 creator A5040049943 @default.
- W4315703372 date "2023-01-01" @default.
- W4315703372 modified "2023-10-02" @default.
- W4315703372 title "S-22-7: GENOMIC ANALYSES OF HYPERTENSION-ASSOCIATED DISEASES ACROSS ETHNIC GROUPS AND SPECIES" @default.
- W4315703372 doi "https://doi.org/10.1097/01.hjh.0000913248.76990.b0" @default.
- W4315703372 hasPublicationYear "2023" @default.
- W4315703372 type Work @default.
- W4315703372 citedByCount "0" @default.
- W4315703372 crossrefType "journal-article" @default.
- W4315703372 hasAuthorship W4315703372A5040049943 @default.
- W4315703372 hasBestOaLocation W43157033721 @default.
- W4315703372 hasConcept C104317684 @default.
- W4315703372 hasConcept C106208931 @default.
- W4315703372 hasConcept C126322002 @default.
- W4315703372 hasConcept C127716648 @default.
- W4315703372 hasConcept C135763542 @default.
- W4315703372 hasConcept C142870003 @default.
- W4315703372 hasConcept C150194340 @default.
- W4315703372 hasConcept C153209595 @default.
- W4315703372 hasConcept C162317418 @default.
- W4315703372 hasConcept C186413461 @default.
- W4315703372 hasConcept C2778086073 @default.
- W4315703372 hasConcept C54355233 @default.
- W4315703372 hasConcept C69991583 @default.
- W4315703372 hasConcept C71924100 @default.
- W4315703372 hasConcept C81941488 @default.
- W4315703372 hasConcept C84393581 @default.
- W4315703372 hasConcept C84951073 @default.
- W4315703372 hasConcept C86803240 @default.
- W4315703372 hasConcept C9287583 @default.
- W4315703372 hasConcept C97425143 @default.
- W4315703372 hasConceptScore W4315703372C104317684 @default.
- W4315703372 hasConceptScore W4315703372C106208931 @default.
- W4315703372 hasConceptScore W4315703372C126322002 @default.
- W4315703372 hasConceptScore W4315703372C127716648 @default.
- W4315703372 hasConceptScore W4315703372C135763542 @default.
- W4315703372 hasConceptScore W4315703372C142870003 @default.
- W4315703372 hasConceptScore W4315703372C150194340 @default.
- W4315703372 hasConceptScore W4315703372C153209595 @default.
- W4315703372 hasConceptScore W4315703372C162317418 @default.
- W4315703372 hasConceptScore W4315703372C186413461 @default.
- W4315703372 hasConceptScore W4315703372C2778086073 @default.
- W4315703372 hasConceptScore W4315703372C54355233 @default.
- W4315703372 hasConceptScore W4315703372C69991583 @default.
- W4315703372 hasConceptScore W4315703372C71924100 @default.
- W4315703372 hasConceptScore W4315703372C81941488 @default.
- W4315703372 hasConceptScore W4315703372C84393581 @default.
- W4315703372 hasConceptScore W4315703372C84951073 @default.
- W4315703372 hasConceptScore W4315703372C86803240 @default.
- W4315703372 hasConceptScore W4315703372C9287583 @default.
- W4315703372 hasConceptScore W4315703372C97425143 @default.
- W4315703372 hasIssue "Suppl 1" @default.
- W4315703372 hasLocation W43157033721 @default.
- W4315703372 hasLocation W43157033722 @default.
- W4315703372 hasOpenAccess W4315703372 @default.
- W4315703372 hasPrimaryLocation W43157033721 @default.
- W4315703372 hasRelatedWork W2075693647 @default.
- W4315703372 hasRelatedWork W2089916071 @default.
- W4315703372 hasRelatedWork W2182957768 @default.
- W4315703372 hasRelatedWork W2581177295 @default.
- W4315703372 hasRelatedWork W2607300493 @default.
- W4315703372 hasRelatedWork W2887733209 @default.
- W4315703372 hasRelatedWork W3082508018 @default.
- W4315703372 hasRelatedWork W4210605760 @default.
- W4315703372 hasRelatedWork W4281675959 @default.
- W4315703372 hasRelatedWork W4308008769 @default.
- W4315703372 hasVolume "41" @default.
- W4315703372 isParatext "false" @default.
- W4315703372 isRetracted "false" @default.
- W4315703372 workType "article" @default.