Cross-Disorder Analysis of Shared Genetic Components Between Cortical Structures and Major Psychiatric Disorders

Zongchang Li; David Li; Ying He; Kangli Wang; Xiaoqian Ma; Xiaogang Chen

doi:10.1093/schbul/sbac019

Cross-Disorder Analysis of Shared Genetic Components Between Cortical Structures and Major Psychiatric Disorders

Schizophr Bull. 2022 Sep 1;48(5):1145-1154. doi: 10.1093/schbul/sbac019.

Authors

Zongchang Li^{1

2

3}, David Li¹, Ying He^{1

2

3}, Kangli Wang⁴, Xiaoqian Ma¹, Xiaogang Chen^{1

2

3}

Affiliations

¹ Department of Psychiatry, The Second Xiangya Hospital, Central South University, Changsha, PR China.
² National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital, Central South University, Changsha, PR China.
³ China National Technology Institute on Mental Disorders & Hunan Key Laboratory of Psychiatry and Mental Health, Mental Health Institute, The Second Xiangya Hospital, Central South University, Changsha, PR China.
⁴ Center for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, PR China.

Abstract

Background and hypothesis: Although large-scale neuroimaging studies have demonstrated similar patterns of structural brain abnormalities across major psychiatric disorders, the underlying genetic etiology behind these similar cross-disorder patterns is not well understood.

Study design: We quantified the extent of shared genetic components between cortical structures and major psychiatric disorders (CS-MPD) by using genome-wide association study (GWAS) summary statistics of 70 cortical structures (surface area and thickness of the whole cortex and 34 cortical regions) and five major psychiatric disorders, consisting of attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BD), major depressive disorder (MDD), and schizophrenia (SCZ). Cross-disorder analyses were then conducted to estimate the degree of similarity in CS-MPD shared genetic components among these disorders.

Study results: The CS-MPD shared genetic components have medium-to-strong positive correlations in ADHD, BD, MDD, and SCZ (r = 0.415 to r = 0.806) while ASD was significantly correlated with ADHD, BD, and SCZ (r = 0.388 to r = 0.403). These pairwise correlations of CS-MPD shared genetic components among disorders were significantly associated with corresponding cross-disorder similarities in cortical structural abnormalities (r = 0.668), accounting for 44% variance. In addition, one latent shared factor consisted primarily of BD, MDD, and SCZ, explaining 62.47% of the total variance in CS-MPD shared genetic components of all disorders.

Conclusions: The current results bridge the gap between shared cross-disorder heritability and shared structural brain abnormalities in major psychiatric disorders, providing important implications for a shared genetic basis of cortical structures in these disorders.

Keywords: cortical structures; cross-disorder similarities; major psychiatric disorders; shared genetic components.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Attention Deficit Disorder with Hyperactivity* / diagnostic imaging
Attention Deficit Disorder with Hyperactivity* / genetics
Autism Spectrum Disorder* / diagnostic imaging
Autism Spectrum Disorder* / genetics
Bipolar Disorder* / diagnostic imaging
Bipolar Disorder* / genetics
Depressive Disorder, Major* / diagnostic imaging
Depressive Disorder, Major* / genetics
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans