Integration of human adipocyte chromosomal interactions with adipose gene expression prioritizes obesity-related genes from GWAS
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 hu...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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Springer Nature
2018
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| _version_ | 1826289173533818880 |
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| author | Pan, D Garske, K Alvarez, M Bhagat, Y Boocock, J Nikkola, E Miao, Z Raulerson, C Cantor, R Civelek, M Glastonbury, C Small, K Boehnke, M Lusis, A Sinsheimer, J Mohlke, K Laakso, M Pajukanta, P Ko, A |
| author_facet | Pan, D Garske, K Alvarez, M Bhagat, Y Boocock, J Nikkola, E Miao, Z Raulerson, C Cantor, R Civelek, M Glastonbury, C Small, K Boehnke, M Lusis, A Sinsheimer, J Mohlke, K Laakso, M Pajukanta, P Ko, A |
| author_sort | Pan, D |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T02:24:52Z |
| format | Journal article |
| id | oxford-uuid:a53fb777-aaeb-47d5-9ff6-e8c4e94b1a92 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T02:24:52Z |
| publishDate | 2018 |
| publisher | Springer Nature |
| record_format | dspace |
| spelling | oxford-uuid:a53fb777-aaeb-47d5-9ff6-e8c4e94b1a922022-03-27T02:39:12ZIntegration of human adipocyte chromosomal interactions with adipose gene expression prioritizes obesity-related genes from GWASJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:a53fb777-aaeb-47d5-9ff6-e8c4e94b1a92EnglishSymplectic Elements at OxfordSpringer Nature2018Pan, DGarske, KAlvarez, MBhagat, YBoocock, JNikkola, EMiao, ZRaulerson, CCantor, RCivelek, MGlastonbury, CSmall, KBoehnke, MLusis, ASinsheimer, JMohlke, KLaakso, MPajukanta, PKo, AIncreased 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. |
| spellingShingle | Pan, D Garske, K Alvarez, M Bhagat, Y Boocock, J Nikkola, E Miao, Z Raulerson, C Cantor, R Civelek, M Glastonbury, C Small, K Boehnke, M Lusis, A Sinsheimer, J Mohlke, K Laakso, M Pajukanta, P Ko, A Integration of human adipocyte chromosomal interactions with adipose gene expression prioritizes obesity-related genes from GWAS |
| title | Integration of human adipocyte chromosomal interactions with adipose gene expression prioritizes obesity-related genes from GWAS |
| title_full | Integration of human adipocyte chromosomal interactions with adipose gene expression prioritizes obesity-related genes from GWAS |
| title_fullStr | Integration of human adipocyte chromosomal interactions with adipose gene expression prioritizes obesity-related genes from GWAS |
| title_full_unstemmed | Integration of human adipocyte chromosomal interactions with adipose gene expression prioritizes obesity-related genes from GWAS |
| title_short | Integration of human adipocyte chromosomal interactions with adipose gene expression prioritizes obesity-related genes from GWAS |
| title_sort | integration of human adipocyte chromosomal interactions with adipose gene expression prioritizes obesity related genes from gwas |
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