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<p>Obesity impairs subcutaneous adipose tissue function, which predisposes to chronic cardiometabolic comorbidities and accelerated biological aging. However, regulatory variants, their target genes and epigenomic landscape underlying this predisposition in each subcutaneous adipose tissue cell-type remain elusive. Our subcutaneous adipose tissue cell-type level <i>cis</i>-expression quantitative trait and colocalization analyses reveal <i>ci</i>s-expression quantitative trait locus variants, regulating 279 genes for 33 cardiometabolic disease and aging traits. Most of these genes are cell-type-specific (90%), led by adipocytes (55%), and missed in previous bulk tissue colocalization studies. Conducting subcutaneous adipose tissue cell-type level epigenome analysis, we discover that the vast majority (81%) of these colocalized cardiometabolic disease and aging risk variants map to the active chromatin compartments that comprise only 45% of the human genome, revealing three-dimensional epigenome in the center of cardiometabolic disease and aging risk. These findings uncover genetic and epigenomic regulation of genes underlying 33 cardiometabolic disease and aging traits in subcutaneous adipose tissue cell-types and offer critical insights into the principal role of three-dimensional chromatin in disease risk.</p>

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Adipose single cell epigenome and transcriptome localize genetic risk for cardiometabolic disease and accelerated aging

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月20日

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  • Seung Hyuk T. Lee,
  • Asha Kar,
  • Kyla Z. Gelev,
  • Zeyuan Johnson Chen,
  • Sankha Subhra Das,
  • Sini Heinonen,
  • Tuure Saarinen,
  • Maija Vaittinen,
  • Dorota Kaminska,
  • Hilkka Peltoniemi,
  • Chongyuan Luo,
  • Anne Juuti,
  • Ville Männistö,
  • Jussi Pihlajamäki,
  • Minna U. Kaikkonen,
  • Kirsi H. Pietiläinen,
  • Brunilda Balliu,
  • Päivi Pajukanta

摘要

Obesity impairs subcutaneous adipose tissue function, which predisposes to chronic cardiometabolic comorbidities and accelerated biological aging. However, regulatory variants, their target genes and epigenomic landscape underlying this predisposition in each subcutaneous adipose tissue cell-type remain elusive. Our subcutaneous adipose tissue cell-type level cis-expression quantitative trait and colocalization analyses reveal cis-expression quantitative trait locus variants, regulating 279 genes for 33 cardiometabolic disease and aging traits. Most of these genes are cell-type-specific (90%), led by adipocytes (55%), and missed in previous bulk tissue colocalization studies. Conducting subcutaneous adipose tissue cell-type level epigenome analysis, we discover that the vast majority (81%) of these colocalized cardiometabolic disease and aging risk variants map to the active chromatin compartments that comprise only 45% of the human genome, revealing three-dimensional epigenome in the center of cardiometabolic disease and aging risk. These findings uncover genetic and epigenomic regulation of genes underlying 33 cardiometabolic disease and aging traits in subcutaneous adipose tissue cell-types and offer critical insights into the principal role of three-dimensional chromatin in disease risk.