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

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

PROVIDER: PRJNA434436 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR8438370_1.fastq.gz	Fastqsanger.gz
	SRR8438370_2.fastq.gz	Fastqsanger.gz
	SRR8438366_1.fastq.gz	Fastqsanger.gz
	SRR8438366_2.fastq.gz	Fastqsanger.gz
	SRR8438367_1.fastq.gz	Fastqsanger.gz

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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.

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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.

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