Publications
1. Hernandez, Leanna M; Kim, Minsoo; Zhang, Pan; Bethlehem, Richard A I; Hoftman, Gil; Loughnan, Robert; Smith, Diana; Bookheimer, Susan Y; Fan, Chun Chieh; Bearden, Carrie E; Thompson, Wesley K; Gandal, Michael J
Multi-ancestry phenome-wide association of complement component 4
variation with psychiatric and brain phenotypes in youth Journal Article
In: Genome Biol., vol. 24, no. 1, pp. 42, 2023.
Abstract | BibTeX | Tags: Brain; Complement; Gene expression; Genetics; Neuroimaging; Psychosis; Schizophrenia
@article{Hernandez2023-yv,
title = {Multi-ancestry phenome-wide association of complement component 4
variation with psychiatric and brain phenotypes in youth},
author = {Leanna M Hernandez and Minsoo Kim and Pan Zhang and Richard A I Bethlehem and Gil Hoftman and Robert Loughnan and Diana Smith and Susan Y Bookheimer and Chun Chieh Fan and Carrie E Bearden and Wesley K Thompson and Michael J Gandal},
year = {2023},
date = {2023-03-01},
journal = {Genome Biol.},
volume = {24},
number = {1},
pages = {42},
abstract = {BACKGROUND: Increased expression of the complement component 4A
(C4A) gene is associated with a greater lifetime risk of
schizophrenia. In the brain, C4A is involved in synaptic pruning;
yet, it remains unclear the extent to which upregulation of C4A
alters brain development or is associated with the risk for
psychotic symptoms in childhood. Here, we perform a
multi-ancestry phenome-wide association study in 7789 children
aged 9-12 years to examine the relationship between genetically
regulated expression (GREx) of C4A, childhood brain structure,
cognition, and psychiatric symptoms. RESULTS: While C4A GREx is
not related to childhood psychotic experiences, cognition, or
global measures of brain structure, it is associated with a
localized reduction in regional surface area (SA) of the
entorhinal cortex. Furthermore, we show that reduced entorhinal
cortex SA at 9-10 years predicts a greater number and severity of
psychosis-like events at 1-year and 2-year follow-up time points.
We also demonstrate that the effects of C4A on the entorhinal
cortex are independent of genome-wide polygenic risk for
schizophrenia. CONCLUSIONS: Our results suggest
neurodevelopmental effects of C4A on childhood medial temporal
lobe structure, which may serve as a biomarker for schizophrenia
risk prior to symptom onset.},
keywords = {Brain; Complement; Gene expression; Genetics; Neuroimaging; Psychosis; Schizophrenia},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: Increased expression of the complement component 4A
(C4A) gene is associated with a greater lifetime risk of
schizophrenia. In the brain, C4A is involved in synaptic pruning;
yet, it remains unclear the extent to which upregulation of C4A
alters brain development or is associated with the risk for
psychotic symptoms in childhood. Here, we perform a
multi-ancestry phenome-wide association study in 7789 children
aged 9-12 years to examine the relationship between genetically
regulated expression (GREx) of C4A, childhood brain structure,
cognition, and psychiatric symptoms. RESULTS: While C4A GREx is
not related to childhood psychotic experiences, cognition, or
global measures of brain structure, it is associated with a
localized reduction in regional surface area (SA) of the
entorhinal cortex. Furthermore, we show that reduced entorhinal
cortex SA at 9-10 years predicts a greater number and severity of
psychosis-like events at 1-year and 2-year follow-up time points.
We also demonstrate that the effects of C4A on the entorhinal
cortex are independent of genome-wide polygenic risk for
schizophrenia. CONCLUSIONS: Our results suggest
neurodevelopmental effects of C4A on childhood medial temporal
lobe structure, which may serve as a biomarker for schizophrenia
risk prior to symptom onset.