IGEN-BP
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB10341 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:We carried out a trans-ethnic genome-wide association and replication study of blood pressure phenotypes amongst up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 novel loci to be associated with blood pressure (P=3.9x10-11 to P=5.0x10-21). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that at some of the loci identified DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 novel loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7, TBX2) function. The novel and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, cardiovascular and all-cause mortality (P=0.04 to 8.6x10-6). Our results provide new evidence for the role of DNA methylation in blood pressure regulation.
| EGAS00001001427 | EGA
Project description:We carried out a genome-wide association and replication study for blood pressure in a two-stage approach (max N = 289,038) with a discovery stage sample of 130,777 East Asian individuals, identifying 19 new genetic loci. We found a significant genetic heterogeneity between East Asian and European-descent populations at several blood pressure loci, conforming to “a common ancestry-specific variant association model”. At 6 unique loci, distinct non-rare (or common) ancestry-specific variants co-localized within the same linkage disequilibrium block despite the significantly discordant direction of effects for the proxy shared variants between the ethnic groups. The genome-wide transethnic correlation of causal-variant effect sizes is 0.898 and 0.851 for systolic and diastolic blood pressure, respectively. Some of the ancestry-specific association signals were also influenced by a selective sweep. Our results provide new evidence for the role of common ancestry-specific variants and natural selection in the occurrence of ethnic differences in complex traits such as blood pressure.
| EGAS00001002991 | EGA
Project description:Kidney samples from three Dahl Salt-sensitive S rats were compared with kidney samples from three S.R(9)x3A congenic rats. Keywords = Blood Pressure Keywords = Quantitative trait locus Keywords = QTL Keywords = hypertension Keywords = rat Keywords = congenic Keywords: parallel sample
2004-09-20 | GSE1775 | GEO
Project description:Musunuru, Brown, Rader, and colleagues of the NHLBI NextGen consortium use multi-ethnic population cohorts of iPSCs and differentiated hepatocyte-like cells, in combination with mouse models, to discover and validate functional DNA variants and genes at blood lipid- associated loci previously identified by genome-wide association studies.
2019-05-15 | GSE131159 | GEO
Project description:The majority of variants associated with complex traits and common diseases identified by genome-wide association studies (GWAS) map to noncoding regions of the genome with unknown regulatory effects. By leveraging ancestrally diverse biobank-scale GWAS data, massively parallel CRISPR screens and single cell transcriptomic and proteomic sequencing, we discovered target genes of noncoding variants for blood trait loci. For 91 GWAS loci, we identified 124 target genes in cis, which were often — but not always — the closest genes to the fine-mapped variant. Using precise variant insertion via base editing, we connect specific variants with gene expression changes. We also identified trans-effect networks of noncoding loci when cis target genes encoded transcription factors or microRNAs, such as GFI1B and miR-142. Trans-regulatory networks were themselves enriched for fine-mapped GWAS variants, demonstrating polygenic contributions to complex traits. Co-expression clustering of GFI1B trans-target genes identifies gene networks specific to different blood cell fates and differentiation stages. This platform will enable massively parallel assays to characterize the target genes and mechanisms of human noncoding variants in both cis and trans.
2021-04-08 | GSE171452 | GEO
Project description:The activation of Long Interspersed Nuclear Element 1 (LINE1/L1) retrotransposons not only leads to genome instability, a factor associated with the development of human diseases, but also plays crucial biological roles in fostering genetic diversity and neuronal functions. Therefore, investigating the regulatory mechanisms that have co-evolved to enable the context-dependent activation or suppression of L1 is important for comprehending pathogenesis associated with aberrant L1 activity. Here we show that two paralogs encoding the pseudokinases NRBP1 and NRBP2 oppositely regulate L1 retrotransposon, via influencing integrity of the L1 ribonucleoprotein complex. We demonstrate that the antagonism between NRBP1 and NRBP2 is not a result of the competitive mechanism, but rather due to targeting NRBP1 to proteasome-mediated degradation by NRBP2, probably through heterodimer formation between these two closely related proteins. In addition, we show that reduced NRBP2 activity is correlated with elevated innate immune response and occurrence of autoimmune diseases, which could also be induced upon L1 activation. Moreover, our phylogenetic analysis suggests NRBP2gene as a duplication of the ancestral NRBP, indicating that evolutionary pressure has favoured this acquired layer of functional fine-tuning of the precursor gene. In summary, our discovery not only identifies NRBP1 and NRBP2 as novel L1 regulators and implicates their involvement in human pathogenesis, but also provides novel insights into the regulatory details arising from gene duplication events.
2025-06-07 | PXD051452 | Pride
Project description:Single-cell elderly blood-CSF atlas implicates peripherally-influenced neuroinflammatory degeneration in normal pressure hydrocephalus
| PRJNA1237269 | ENA
Project description:The MESA Epigenomics and Transcriptomics Study has been launched to investigate potential gene expression regulatory methylation sites in humans by examining the association between CpG methylation and gene expression in purified human monocytes from a large study population (community-dwelling participants in the Multi-Ethnic Study of Atherosclerosis (MESA)). The MESA Epigenomics and Transcriptomics Study was funded by a National Heart, Lung and Blood Institute grant (R01HL101250) through the NIH Roadmap Epigenomics Program in 2009.
2014-11-24 | GSE56046 | GEO
Project description:The MESA Epigenomics and Transcriptomics Study has been launched to investigate potential gene expression regulatory methylation sites in humans by examining the association between CpG methylation and gene expression in purified human monocytes from a large study population (community-dwelling participants in the Multi-Ethnic Study of Atherosclerosis (MESA)). The MESA Epigenomics and Transcriptomics Study was funded by a National Heart, Lung and Blood Institute grant (R01HL101250) through the NIH Roadmap Epigenomics Program in 2009.
2014-11-24 | GSE56045 | GEO