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

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. Overall design: ATAC-seq on adipose tissue from three individuals from the METSIM study and two replicates of SGBS preadipocytes and three replicates of differentiated SGBS adipocytes Authors' note: Please note that the METSIM study does not allow unrestricted access to fastq files and other files that allow individual identity to be determined. Therefore, the raw data for the adipose tissue ATAC-seq samples will be submitted to dbGaP where researchers can request access to them. We do have permission to share ATAC-seq peaks and bigWig signal tracks because it is not possible to identify an individual from these files.