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

A pH-eQTL interaction at the RIT2-SYT4 Parkinson’s disease risk locus in the substantia nigra

Sejal Patel, Derek Howard, Leon French
doi: https://doi.org/10.1101/2020.12.16.423140
Sejal Patel
1Krembil Centre for Neuroinformatics, Centre for Addiction and Mental Health, Toronto, ON, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Derek Howard
1Krembil Centre for Neuroinformatics, Centre for Addiction and Mental Health, Toronto, ON, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Leon French
1Krembil Centre for Neuroinformatics, Centre for Addiction and Mental Health, Toronto, ON, Canada
2Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Canada
3Department of Psychiatry, University of Toronto, Toronto
4Institute for Medical Science, University of Toronto, Toronto, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: leonfrench@gmail.com
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Data/Code
  • Preview PDF
Loading

Abstract

Parkinson’s disease (PD) causes severe motor and cognitive disabilities that result from the progressive loss of dopamine neurons in the substantia nigra. The rs12456492 variant in the RIT2 gene has been repeatedly associated with increased risk for Parkinson’s disease. From a transcriptomic perspective, a meta-analysis found that RIT2 gene expression is correlated with pH in the human brain. To assess these pH associations in relation to PD risk, we examined the two datasets that assayed rs12456492, gene expression, and pH in the postmortem human brain. Using the BrainEAC dataset, we replicate the positive correlation between RIT2 gene expression and pH in the human brain (n=100). Furthermore, we found that the relationship between expression and pH is influenced by rs12456492. When tested across ten brain regions, this interaction is specifically found in the substantia nigra. A similar association was found for the co-localized SYT4 gene. In addition, SYT4 associations are stronger in a combined model with both genes, and the SYT4 interaction appears to be specific to males. In the GTEx dataset, the pH associations involving rs12456492 and expression of either SYT4 and RIT2 was not seen. This null finding may be due to the short postmortem intervals (PMI) of the GTEx tissue samples. In the BrainEAC data, we tested the effect of PMI and only observed the interactions in the longer PMI samples. These previously unknown associations suggest novel mechanistic roles for rs12456492, RIT2, and SYT4 in the regulation of pH in the substantia nigra.

Competing Interest Statement

LF owns shares in Cortexyme Inc., a company that is developing treatments for neurodegenerative disease. The other authors declare no conflict of interest.

Footnotes

  • Corrected accidental omission of two references. Added conflict of interest.

  • https://github.com/Sejal24/PD_Manuscript_RIT2_SYT4_pH

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-NC-ND 4.0 International license.
Back to top
PreviousNext
Posted June 04, 2021.
Download PDF
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.
A pH-eQTL interaction at the RIT2-SYT4 Parkinson’s disease risk locus in the substantia nigra
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
A pH-eQTL interaction at the RIT2-SYT4 Parkinson’s disease risk locus in the substantia nigra
Sejal Patel, Derek Howard, Leon French
bioRxiv 2020.12.16.423140; doi: https://doi.org/10.1101/2020.12.16.423140
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
A pH-eQTL interaction at the RIT2-SYT4 Parkinson’s disease risk locus in the substantia nigra
Sejal Patel, Derek Howard, Leon French
bioRxiv 2020.12.16.423140; doi: https://doi.org/10.1101/2020.12.16.423140

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

  • Neuroscience
Subject Areas
All Articles
  • Animal Behavior and Cognition (4087)
  • Biochemistry (8766)
  • Bioengineering (6480)
  • Bioinformatics (23346)
  • Biophysics (11751)
  • Cancer Biology (9149)
  • Cell Biology (13255)
  • Clinical Trials (138)
  • Developmental Biology (7417)
  • Ecology (11369)
  • Epidemiology (2066)
  • Evolutionary Biology (15088)
  • Genetics (10402)
  • Genomics (14011)
  • Immunology (9122)
  • Microbiology (22050)
  • Molecular Biology (8780)
  • Neuroscience (47373)
  • Paleontology (350)
  • Pathology (1420)
  • Pharmacology and Toxicology (2482)
  • Physiology (3704)
  • Plant Biology (8050)
  • Scientific Communication and Education (1431)
  • Synthetic Biology (2209)
  • Systems Biology (6016)
  • Zoology (1250)