Interethnic comparability in blood pressure GWAS
Ontology highlight
ABSTRACT:
PROVIDER: EGAS00001002991 | EGA |
REPOSITORIES: EGA
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:Single-cell RNA-seq (scRNA-seq) of pancreatic islets have reported on α- and β-cell gene expression in mice and subjects of predominantly European ancestry. We aimed to assess these findings in East-Asian islet-cells. 448 islet-cells were captured from three East-Asian non-diabetic subjects for scRNA-seq. Hierarchical clustering using pancreatic cell lineage genes was used to assign cells into cell-types. Differentially expressed transcripts between α- and β-cells were detected using ANOVA and in silico replications of mouse and human islet cell genes were performed. We identified 118 α, 105 β, 6 δ endocrine cells and 47 exocrine cells. Besides INS and GCG, 26 genes showed differential expression between α- and β-cells. 10 genes showed concordant expression as reported in rodents, while FAM46A was significantly discordant. Comparing our East-Asian data with data from primarily European subjects, we replicated several genes implicated in nuclear receptor activations, acute phase response pathway, glutaryl-CoA/tryptophan degradations and EIF2/AMPK/mTOR signaling. Additionally, we identified protein ubiquitination to be associated among East-Asian β-cells. We report on East-Asian α- and β-cell gene signatures and substantiate several genes/pathways. We identify expression signatures in East-Asian β-cells that perhaps reflects increased susceptibility to cell-death and warrants future validations to fully appreciate their role in East-Asian diabetes pathogenesis.
2017-08-11 | GSE97655 | GEO
Project description:Atrial fibrillation (AF) is the most common arrhythmia in the world, and is linked to significant morbidity and mortality. Despite advances in the treatment and management of AF, important challenges remain for patients. Human genetics can provide strong therapeutic candidates, but the identification of the causal genes and their functions is difficult. Here, we apply an AF fine-mapping strategy that leverages results from a cross-ancestry genome-wide association study (GWAS), expression quantitative trait loci (eQTLs) from left atrial appendages (LAA) obtained from two cohorts with distinct ancestry (European and East Asian), and a paired RNAseq and ATACseq LAA single-nucleus assay (sn-multiome). We found that AF-associated LAA eQTLs are largely consistent across ancestries. At ten AF loci, our co-localization and fine-mapping analyses implicated 14 genes. Furthermore, by integrating our LAA sn-multiome data and other epigenomic datasets with our fine-mapping results, we identified four primary candidate causal AF variants, including rs7612445 at GNB4 and rs242557 at MAPT, for which we propose molecular mechanisms of AF-association at the cellular level. Finally, we showed that the repression of the strongest AF-associated eQTL gene, LINC01629, in human embryonic stem cell-derived cardiomyocytes using CRISPR inhibition results in the dysregulation of pathways linked to genes involved in the development of atrial tissue and the cardiac conduction system (e.g. HCN4, PITX2 and TBX5).
2024-07-09 | GSE271839 | GEO
Project description:Atrial fibrillation (AF) is the most common arrhythmia in the world, and is linked to significant morbidity and mortality. Despite advances in the treatment and management of AF, important challenges remain for patients. Human genetics can provide strong therapeutic candidates, but the identification of the causal genes and their functions is difficult. Here, we apply an AF fine-mapping strategy that leverages results from a cross-ancestry genome-wide association study (GWAS), expression quantitative trait loci (eQTLs) from left atrial appendages (LAA) obtained from two cohorts with distinct ancestry (European and East Asian), and a paired RNAseq and ATACseq LAA single-nucleus assay (sn-multiome). We found that AF-associated LAA eQTLs are largely consistent across ancestries. At ten AF loci, our co-localization and fine-mapping analyses implicated 14 genes. Furthermore, by integrating our LAA sn-multiome data and other epigenomic datasets with our fine-mapping results, we identified four primary candidate causal AF variants, including rs7612445 at GNB4 and rs242557 at MAPT, for which we propose molecular mechanisms of AF-association at the cellular level. Finally, we showed that the repression of the strongest AF-associated eQTL gene, LINC01629, in human embryonic stem cell-derived cardiomyocytes using CRISPR inhibition results in the dysregulation of pathways linked to genes involved in the development of atrial tissue and the cardiac conduction system (e.g. HCN4, PITX2 and TBX5).
2024-07-09 | GSE238242 | GEO
Project description:Despite being located at the crossroads of Asia, genetics of the Afghanistan populations have been largely overlooked. It is currently inhabited by five major ethnic populations: Pashtun, Tajik, Hazara, Uzbek and Turkmen. Here we present autosomal from a subset of our samples, mitochondrial and Y- chromosome data from over 500 Afghan samples among these 5 ethnic groups. This Afghan data was supplemented with the same Y-chromosome analyses of samples from Iran, Kyrgyzstan, Mongolia and updated Pakistani samples (HGDP-CEPH). The data presented here was integrated into existing knowledge of pan-Eurasian genetic diversity. The pattern of genetic variation, revealed by structure-like and Principal Component analyses and Analysis of Molecular Variance indicates that the people of Afghanistan are made up of a mosaic of components representing various geographic regions of Eurasian ancestry. The absence of a major Central Asian-specific component indicates that the Hindu Kush, like the gene pool of Central Asian populations in general, is a confluence of gene flows rather than a source of distinctly autochthonous populations that have arisen in situ: a conclusion that is reinforced by the phylogeography of both haploid loci. 24 samples were analysed with the Illumina platform Human660W-Quad v1.0 Genotyping BeadChip and are described herein.
2013-11-04 | E-GEOD-51158 | biostudies-arrayexpress
Project description:BACKGORUND & AIMS: Hepatocellular carcinoma (HCC) disproportionally affects Asian Americans due to the high prevalence of chronic hepatitis B virus (HBV) infection and among Asian ethnic groups. The Hmong are diagnosed with HCC at a younger age, with more advanced stage disease, and have the highest cause specific mortality of any Asian ethnic group. Poor survival from HCC has also been associated with differential gene expression in HCC tumors leading us to hypothesize that quantitative traits loci lead to differences in the expression of genes in Hmong which reduce their HCC survival. METHODS: We performed bulk RNA-sequencing of whole blood total RNA from HBV-infected Hmong (n=30) and non-Hmong Asians (Chinese (n=46), and Vietnamese (n=19)). RESULTS: No significant differences between groups were identified in demographic, clinical, or viral factors. A total of 1,491 differentially-expressed transcripts (DETs) were identified across the 3 ethnic groups. When restricted to those with an HBV viral load >2,000 IU/L, 768 DETs were identified and accurately separated individuals by ethincity. Among 273 DETs identified by functional enrichment and pathway analysis and associated with annotated sets of HCC-related genes, 9 were found in 2 gene sets highly expressed in HCC with poor survival. After adjusting for age and sex, expression levels of 4 of these, including CD164, ECT2, HDAC2, and UBE2T, remained significantly elevated in Hmong compared to Chinese and Vietnamese. CONCLUSIONS: These results suggest expression quantitative trait loci predispose Hmong to a more agrressive form of HCC and may explain the poor survival among this Asian ethnic group.
2021-11-01 | GSE173897 | GEO
Project description:There exists a common deletion polymorphism on the genetic loci of APOBEC3B and this polymorphism exist in ~37% of East Asians and ~7% of Europeans. Germline APOBEC3B deletion has bee27233495n shown to confer modest risk to breast cancer in both East Asian women and women of European descent We performed expression profiling by array to investigate the significantly differentially expressed genes and enriched gene sets in APOBEC3B-null vs. APOBEC3B breast cancers
2016-09-18 | GSE73540 | GEO
Project description:Despite being located at the crossroads of Asia, genetics of the Afghanistan populations have been largely overlooked. It is currently inhabited by five major ethnic populations: Pashtun, Tajik, Hazara, Uzbek and Turkmen. Here we present autosomal from a subset of our samples, mitochondrial and Y- chromosome data from over 500 Afghan samples among these 5 ethnic groups. This Afghan data was supplemented with the same Y-chromosome analyses of samples from Iran, Kyrgyzstan, Mongolia and updated Pakistani samples (HGDP-CEPH). The data presented here was integrated into existing knowledge of pan-Eurasian genetic diversity. The pattern of genetic variation, revealed by structure-like and Principal Component analyses and Analysis of Molecular Variance indicates that the people of Afghanistan are made up of a mosaic of components representing various geographic regions of Eurasian ancestry. The absence of a major Central Asian-specific component indicates that the Hindu Kush, like the gene pool of Central Asian populations in general, is a confluence of gene flows rather than a source of distinctly autochthonous populations that have arisen in situ: a conclusion that is reinforced by the phylogeography of both haploid loci.
2013-11-04 | GSE51158 | GEO
Project description:As Asians are underrepresented across many omics databases limiting the potential of precision medicine of the global population. It is thus important for multi-omics derived quantitative trait loci (QTLs) to fill the knowledge gap of complex traits in the Asian ancestry. Integrating omics data from genomics and epigenomics (including DNA methylation and RNA-seq from blood), we developed iMOMdb, an open-acesss database to enhance disease prediction models and precision medicine outcomes in Asian pregnant women.
2022-10-04 | GSE182409 | GEO
Project description:(1) In clinical practice and biomedical research populations are often divided categorically into distinct racial and ethnic groups. In reality, these categories comprise diverse groups with highly heterogeneous histories, cultures, traditions, religions, as well as social and environmental exposures. While the factors captured by these categories contribute to clinical practice and biomedical research, the use of race/ethnicity is widely debated. As a response to this debate, genetic ancestry has been suggested as a complement or alternative to this categorization. However, few studies have examined the effect of genetic ancestry, racial/ethnic identity, and environmental exposures on biological processes. Herein, we examine the contribution of self-identification within ethnicity, genetic ancestry, and environmental exposures on epigenetic modification of DNA methylation, a phenomenon affected by both genetic and environmental factors. We typed over 450,000 variably methylated CpG sites in primary whole blood of 573 individuals of Mexican and Puerto Rican descent who also had high-density genotype data. We found that methylation levels at a large number of CpG sites were significantly associated with ethnicity even when adjusting for genetic ancestry. In addition, we found an enrichment of ethnicity-associated sites amongst loci previously associated with environmental and social exposures. Interestingly, one of the strongest associated sites is driven by the Duffy Null blood type variant, demonstrating a new function of the locus in lymphocytes. Overall, the methylation changes associated with race/ethnicity, driven by both genes and environment, highlight the importance of measuring and accounting for both self-identified race/ethnicity and genetic ancestry in clinical and biomedical studies and the benefits of studying diverse populations. (2) In epigenome-wide association studies (EWAS), different methylation profiles of distinct cell-types may lead to false discoveries. We introduce ReFACTor, a method based on principal component analysis (PCA) for the correction of cell-type heterogeneity in EWAS. ReFACTor does not require knowledge of the cell counts, and it obtains improved estimates of the cell-type composition, resulting in improved power and control for false positives in EWAS. Bisulphite converted DNA from 573 samples were hybridised to the Illumina Infinium 450k Human Methylation Beadchip and a complete blood count with automated white blood cell differential was performed by automated flow cytometry for 95 of the samples.
2016-02-29 | E-GEOD-77716 | biostudies-arrayexpress