Connecting genomic results for psychiatric disorders to human brain cell types and regions reveals convergence with functional connectivity

Shuyang Yao, Arvid Harder, Fahimeh Darki, Yu-Wei Chang, Ang Li, Kasra Nikouei, Giovanni Volpe, Johan N. Lundström, Jian Zeng, Naomi R. Wray, Yi Lu, Patrick F. Sullivan () and Jens Hjerling-Leffler ()
Additional contact information
Shuyang Yao: Karolinska Institutet
Arvid Harder: Karolinska Institutet
Fahimeh Darki: Karolinska Institutet
Yu-Wei Chang: University of Gothenburg
Ang Li: University of Queensland
Kasra Nikouei: Karolinska Institutet
Giovanni Volpe: University of Gothenburg
Johan N. Lundström: Karolinska Institutet
Jian Zeng: University of Queensland
Naomi R. Wray: University of Queensland
Yi Lu: Karolinska Institutet
Patrick F. Sullivan: Karolinska Institutet
Jens Hjerling-Leffler: Karolinska Institutet

Nature Communications, 2025, vol. 16, issue 1, 1-18

Abstract: Abstract Identifying cell types and brain regions critical for psychiatric disorders and brain traits is essential for targeted neurobiological research. By integrating genomic insights from genome-wide association studies with a comprehensive single-cell transcriptomic atlas of the adult human brain, we prioritized specific neuronal clusters significantly enriched for the SNP-heritabilities for schizophrenia, bipolar disorder, and major depressive disorder along with intelligence, education, and neuroticism. Extrapolation of cell-type results to brain regions reveals the whole-brain impact of schizophrenia genetic risk, with subregions in the hippocampus and amygdala exhibiting the most significant enrichment of SNP-heritability. Using functional MRI connectivity, we further confirmed the significance of the central and lateral amygdala, hippocampal body, and prefrontal cortex in distinguishing schizophrenia cases from controls. Our findings underscore the value of single-cell transcriptomics in understanding the polygenicity of psychiatric disorders and suggest a promising alignment of genomic, transcriptomic, and brain imaging modalities for identifying common biological targets.

Date: 2025
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-55611-1 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-024-55611-1

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-55611-1

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().