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Chromatin accessibility and gene expression during adipocyte differentiation identify context-dependent effects at cardiometabolic GWAS loci

ABSTRACT: Chromatin accessibility and gene expression during adipocyte differentiation identify context-dependent effects at cardiometabolic GWAS loci

PROVIDER: PRJNA740373 | ENA |

REPOSITORIES: ENA

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Chromatin accessibility and gene expression during adipocyte differentiation identify context-dependent effects at cardiometabolic GWAS loci [RNA-seq]

Project description:Chromatin accessibility and gene expression in relevant cell contexts can guide identification of regulatory elements and mechanisms at genome-wide association study (GWAS) loci. To identify regulatory elements that display differential activity across adipocyte differentiation, we performed ATAC-seq and RNA-seq in a cell model of preadipocytes and adipocytes at days 4 and 14 of differentiation. For comparison, we created a consensus map of ATAC-seq peaks in 11 subcutaneous adipose tissue samples. A set of 15,919 adipocyte-dependent peaks showed stronger enrichment (60.1%) of adipocyte nuclei enhancers than 51,855 adipose tissue peaks (44.6%) or 18,244 preadipocyte-dependent peaks (11.5%). We linked context-dependent peaks to genes based on adipocyte promoter capture Hi-C data, overlap with adipose eQTL variants, and differential gene expression. Of 16,167 context-dependent peaks that could be linked to a gene, 5,184 were linked by two or more strategies to 1,675 genes. Among GWAS loci for cardiometabolic traits, adipocyte peaks showed the strongest enrichment for waist-to-hip ratio, coronary artery disease, and HDL-cholesterol, while adipose tissue peaks also showed significant enrichment for LDL-cholesterol and triglyceride levels. We identified 666 peaks linked to 507 genes by two or more methods and overlapping a GWAS signal, suggesting a regulatory mechanism at these loci. At one GWAS locus for palmitoleic acid, rs603424 was located in an adipocyte-dependent peak linked to SCD and exhibited allelic differences in transcriptional activity in adipocytes (P=0.003) but not preadipocytes (P=0.09). These results demonstrate that context-dependent peaks and genes can guide discovery of regulatory variants at GWAS loci and aid identification of regulatory mechanisms.

2021-08-01 | GSE178795 | GEO

Chromatin accessibility and gene expression during adipocyte differentiation identify context-dependent effects at cardiometabolic GWAS loci [ATAC-seq]

2021-08-01 | GSE178794 | GEO

Chromatin accessibility and gene expression during adipocyte differentiation identify context-dependent effects at cardiometabolic GWAS loci [RNA-seq]

Project description:Chromatin accessibility and gene expression during adipocyte differentiation identify context-dependent effects at cardiometabolic GWAS loci [RNA-seq]

| PRJNA740463 | ENA

Chromatin accessibility and gene expression during adipocyte differentiation identify context-dependent effects at cardiometabolic GWAS loci [ATAC-seq]

Project description:Chromatin accessibility and gene expression during adipocyte differentiation identify context-dependent effects at cardiometabolic GWAS loci [ATAC-seq]

| PRJNA740464 | ENA

Chromatin accessibility and gene expression during adipocyte differentiation identify context-dependent effects at cardiometabolic GWAS loci

Project description: Not available

| S-EPMC8570510 | biostudies-literature

Chromatin accessibility and gene expression during adipocyte differentiation identify context-dependent effects at cardiometabolic GWAS loci

Project description:This SuperSeries is composed of the SubSeries listed below.

2021-08-01 | GSE178796 | GEO

Open chromatin profiling in adipose tissue marks genomic regions with functional roles in cardiometabolic traits

Project description:Identifying the regulatory mechanisms of genome-wide association study (GWAS) loci affecting adipose tissue has been restricted due to limited characterization of adipose transcriptional regulatory elements. We profiled chromatin accessibility in three frozen human subcutaneous adipose tissue needle biopsies and preadipocytes and adipocytes from the Simpson Golabi-Behmel Syndrome (SGBS) cell strain using an assay for transposase-accessible chromatin (ATAC-seq). We identified 68,571 representative accessible chromatin regions (peaks) across adipose tissue samples (FDR<5%). GWAS loci for eight cardiometabolic traits were enriched in these peaks (p<0.005), with the strongest enrichment for waist-hip ratio. Of 110 recently described cardiometabolic GWAS loci colocalized with adipose tissue eQTLs, 59 loci had one or more variants overlapping an adipose tissue peak. Annotated variants at the SNX10 waist-hip ratio locus and the ATP2A1-SH2B1 body mass index locus showed allelic differences in regulatory assays. These adipose tissue accessible chromatin regions elucidate genetic variants that may alter adipose tissue function to impact cardiometabolic traits.

2019-01-01 | GSE110734 | GEO

RNA-seq of in vitro differentiated human abdominal and gluteal adipocyte cell lines following doxycycline induced RSPO3-knockdown

Project description:GWAS studies and our own work have identified RSPO3 as a gene modulating human body fat distribution. The GWAS signal at RSPO3 is coincident with an eQTL in mature adipocytes. To assess the effects of RSPO3 on abdominal and gluteal adipocyte biology, we undertook inducible RSPO3-knockdown in in vitro differentiated immortalized human abdominal and gluteal adipocyte cell lines (DFAT cells).

2020-06-01 | GSE149294 | GEO

Biological constraints on GWAS SNPs at suggestive significance thresholds reveal true BMI loci [hMSC_adipocytes_captureC]

Project description:We investigated whether intersecting functional genomic data (ATAC-seq + promoter focused Capture C) with increasingly powered publically available GWAS for Body Mass Index and Waist to Hip Ratio could identify additional true postiive subsignficant signals (5x10-8< P value < 5x10-4) without increasing the GWAS sample size

2021-01-16 | GSE164911 | GEO

Biological constraints on GWAS SNPs at suggestive significance thresholds reveal true BMI loci [hMSC_adipocytes_atacseq]

2021-01-16 | GSE164745 | GEO

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