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

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

Department of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.Department of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. · pubmed

Paper

Abstract

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.

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Research summary

The paper claims that specific genetic and epigenomic factors in subcutaneous adipose tissue are linked to cardiometabolic diseases and aging traits. This research is relevant as it explores the underlying genetic and epigenomic mechanisms that contribute to aging and age-related diseases, potentially addressing root causes rather than just symptoms.

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