Transcriptional and imaging-genetic association of cortical interneurons, brain function, and schizophrenia risk.

Nature Communications
Kevin M AndersonAvram J Holmes

Abstract

Inhibitory interneurons orchestrate information flow across the cortex and are implicated in psychiatric illness. Although interneuron classes have unique functional properties and spatial distributions, the influence of interneuron subtypes on brain function, cortical specialization, and illness risk remains elusive. Here, we demonstrate stereotyped negative correlation of somatostatin and parvalbumin transcripts within human and non-human primates. Cortical distributions of somatostatin and parvalbumin cell gene markers are strongly coupled to regional differences in functional MRI variability. In the general population (n = 9,713), parvalbumin-linked genes account for an enriched proportion of heritable variance in in-vivo functional MRI signal amplitude. Single-marker and polygenic cell deconvolution establish that this relationship is spatially dependent, following the topography of parvalbumin expression in post-mortem brain tissue. Finally, schizophrenia genetic risk is enriched among interneuron-linked genes and predicts cortical signal amplitude in parvalbumin-biased regions. These data indicate that the molecular-genetic basis of brain function is shaped by interneuron-related transcripts and may capture individual di...Continue Reading

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Citations

Sep 23, 2020·Proceedings of the National Academy of Sciences of the United States of America·Kevin M AndersonAvram J Holmes
Dec 18, 2020·ELife·Golia ShafieiBratislav Misic
Dec 29, 2020·Journal of Neuroimaging : Official Journal of the American Society of Neuroimaging·Magdalena MroczekWadid Sirry
Feb 25, 2021·Proceedings of the National Academy of Sciences of the United States of America·Kevin M AndersonAvram J Holmes
Apr 4, 2021·International Journal of Molecular Sciences·Ágnes DombiGábor Pozsgai
Jun 1, 2021·Frontiers in Cell and Developmental Biology·Muhammad JahangirXiao-Ping Wang
May 27, 2021·Seminars in Cell & Developmental Biology·Anne Teissier, Alessandra Pierani
Jun 8, 2021·International Journal of Psychophysiology : Official Journal of the International Organization of Psychophysiology·Victor N Almeida
Jun 28, 2021·Brain Structure & Function·Ellie A BucherMatthew T K Kirkcaldie
Sep 12, 2021·Seminars in Cell & Developmental Biology·Lena Palaniyappan
Oct 14, 2021·European Journal of Histochemistry : EJH·Gianpaolo Antonio BasileAlberto Cacciola
Nov 6, 2021·Nature Communications·Xiaolu KongB T Thomas Yeo
Nov 17, 2021·ELife·Ross D MarkelloBratislav Misic

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Methods Mentioned

BETA
RNAseq
snDrop-Seq

Software Mentioned

AFNI
GCTA
HCP workbench
MCFLIRT
REML
Plink
PRSice
Brainspan
fastGWA
biomaRt

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