Integration of Human Adipocyte Chromosomal Interactions with Adipose Gene Expression Prioritizes Obesity-related Genes from GWAS
Nature Communicationsvolume. 2018-4-17;9(1):1512.
- Abstract
- Increased adiposity is a hallmark of obesity and overweight, which affect 2.2 billion people world-wide. Understanding the genetic and molecular mechanisms that underlie obesity-related phenotypes can help to improve treatment options and drug development. Here we perform promoter Capture Hi–C in human adipocytes to investigate interactions between gene promoters and distal elements as a transcription-regulating mechanism contributing to these phenotypes. We find that promoter-interacting elements in human adipocytes are enriched for adipose-related transcription factor motifs, such as PPARG and CEBPB, and contribute to heritability of cis-regulated gene expression. We further intersect these data with published genome-wide association studies for BMI and BMI-related metabolic traits to identify the genes that are under genetic cis regulation in human adipocytes via chromosomal interactions. This integrative genomics approach identifies four cis-eQTL-eGene relationships associated with BMI or obesity-related traits, including rs4776984 and MAP2K5, which we further confirm by EMSA, and highlights 38 additional candidate genes.
- Consortium data used in this publication
- The human primary adipocyte Capture Hi–C data are available at GEO (Accession ID: GSE110619)
- Datasets
- TSTSR423QSN, DSR355DOK