Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Mapping heritability of obesity by brain cell types

View ORCID ProfilePascal N Timshel, View ORCID ProfileJonatan J Thompson, View ORCID ProfileTune H Pers
doi: https://doi.org/10.1101/2020.01.27.920033
Pascal N Timshel
Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Pascal N Timshel
Jonatan J Thompson
Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Jonatan J Thompson
Tune H Pers
Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Tune H Pers
  • For correspondence: tune.pers@sund.ku.dk
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Data/Code
  • Preview PDF
Loading

Abstract

The underlying cell types mediating predisposition to obesity remain largely obscure. Here we first integrated recently published single-cell RNA-sequencing (scRNA-seq) data from >380 peripheral and nervous system cell types spanning 19 mouse organs with body mass index (BMI) genome-wide association study (GWAS) data from >450,000 individuals. Leveraging a novel strategy for integrating scRNA-seq data with GWAS data, we identified 22, exclusively neuronal, cell types from the subthalamus, midbrain, hippocampus, thalamus, cortex, pons, medulla, pallidum that were significantly enriched for BMI heritability (P<1.6×10-4). Using genes harboring coding mutations leading to syndromic forms of obesity, we replicate four midbrain cell types from the anterior pretectal nucleus, superior nucleus, periaqueductal gray and pallidum (P<1.7×10-4). Testing an additional set of 347 hypothalamic cell types, ventromedial hypothalamic steroidogenic-factor 1 (SF1) and cholecystokinin b receptor (CCKBR)-expressing neurons (P=4.9×10-5) previously implicated in energy homeostasis and glucose control and three cell types from the preoptic area of the hypothalamus and the lateral hypothalamus enriched for BMI GWAS associations (P<4.9×10-5). Together, our results suggest brain nuclei regulating integration of sensory stimuli, learning and memory are likely to play a key role in obesity and provide testable hypotheses for mechanistic follow-up studies.

Footnotes

  • https://github.com/perslab/timshel-bmicelltypes

  • https://github.com/perslab/CELLEX

  • https://github.com/perslab/CELLECT

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
Back to top
PreviousNext
Posted January 28, 2020.
Download PDF

Supplementary Material

Data/Code
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Mapping heritability of obesity by brain cell types
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
Share
Mapping heritability of obesity by brain cell types
Pascal N Timshel, Jonatan J Thompson, Tune H Pers
bioRxiv 2020.01.27.920033; doi: https://doi.org/10.1101/2020.01.27.920033
Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
Citation Tools
Mapping heritability of obesity by brain cell types
Pascal N Timshel, Jonatan J Thompson, Tune H Pers
bioRxiv 2020.01.27.920033; doi: https://doi.org/10.1101/2020.01.27.920033

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Genetics
Subject Areas
All Articles
  • Animal Behavior and Cognition (1647)
  • Biochemistry (2739)
  • Bioengineering (1907)
  • Bioinformatics (10243)
  • Biophysics (4183)
  • Cancer Biology (3218)
  • Cell Biology (4538)
  • Clinical Trials (135)
  • Developmental Biology (2840)
  • Ecology (4460)
  • Epidemiology (2041)
  • Evolutionary Biology (7231)
  • Genetics (5476)
  • Genomics (6813)
  • Immunology (2388)
  • Microbiology (7483)
  • Molecular Biology (2992)
  • Neuroscience (18584)
  • Paleontology (136)
  • Pathology (472)
  • Pharmacology and Toxicology (780)
  • Physiology (1149)
  • Plant Biology (2706)
  • Scientific Communication and Education (680)
  • Synthetic Biology (888)
  • Systems Biology (2846)
  • Zoology (468)