
==== Front
bioRxiv
BIORXIV
bioRxiv
2692-8205
Cold Spring Harbor Laboratory

10.1101/2024.09.10.610174
preprint
1
Article
Genetic regulation of microRNAs in the older adult brain and their contribution to neuropsychiatric conditions
Vattathil Selina M http://orcid.org/0000-0001-5616-4184

Gerasimov Ekaterina S
Canon Se Min
Lori Adriana http://orcid.org/0000-0001-8686-0148

Tan Sarah Sze Min
Kim Paul J
Liu Yue
Lai Eric C http://orcid.org/0000-0002-8432-5851

Bennett David A C.
Wingo Thomas S http://orcid.org/0000-0002-7679-6282

Wingo Aliza P http://orcid.org/0000-0002-6360-6726

12 9 2024
2024.09.10.610174https://creativecommons.org/licenses/by-nd/4.0/ This work is licensed under a Creative Commons Attribution-NoDerivatives 4.0 International License, which allows reusers to copy and distribute the material in any medium or format in unadapted form only, and only so long as attribution is given to the creator. The license allows for commercial use.
http://biorxiv.org/lookup/doi/10.1101/2024.09.10.610174
nihpp-2024.09.10.610174.pdf
MicroRNAs are essential post-transcriptional regulators of gene expression and involved in many biological processes; however, our understanding of their genetic regulation and role in brain illnesses is limited. Here, we mapped brain microRNA expression quantitative trait loci (miR-QTLs) using genome-wide small RNA sequencing profiles from dorsolateral prefrontal cortex (dlPFC) samples of 604 older adult donors of European ancestry. miR-QTLs were identified for 224 miRNAs (48% of 470 tested miRNAs) at false discovery rate < 1%. We found that miR-QTLs were enriched in brain promoters and enhancers, and that intragenic miRNAs often did not share QTLs with their host gene. Additionally, we integrated the brain miR-QTLs with results from 16 GWAS of psychiatric and neurodegenerative diseases using multiple independent integration approaches and identified four miRNAs that contribute to the pathogenesis of bipolar disorder, major depression, post-traumatic stress disorder, schizophrenia, and Parkinson's disease. This study provides novel insights into the contribution of miRNAs to the complex biological networks that link genetic variation to disease.
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pmc
