Structural brain imaging studies offer clues about the effects of the shared genetic etiology among neuropsychiatric disorders

Nevena V Radonjić,Sanjay M Sisodiya,Paula Rovira,Stephen V Faraone,Dick J Veltman,Ole Andreassen,Odile A Van Den Heuvel,Barbara Franke,Paul Thompson,Christopher R K Ching,Jonathan L Hess,Daan Van Rooij,Jan K Buitelaar,Neda Jahanshad,Lianne Schmaal,Carrie Mcdonald,Dan J Stein,Theo G M Van Erp,Martine Hoogman

doi:10.1038/s41380-020-01002-z

Abstract

Genomewide association studies have found significant genetic correlations among many neuropsychiatric disorders. In contrast, we know much less about the degree to which structural brain alterations are similar among disorders and, if so, the degree to which such similarities have a genetic etiology. From the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) consortium, we acquired standardized mean differences (SMDs) in regional brain volume and cortical thickness between cases and controls. We had data on 41 brain regions for: attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BD), epilepsy, major depressive disorder (MDD), obsessive compulsive disorder (OCD), and schizophrenia (SCZ). These data had been derived from 24,360 patients and 37,425 controls. The SMDs were significantly correlated between SCZ and BD, OCD, MDD, and ASD. MDD was positively correlated with BD and OCD. BD was positively correlated with OCD and negatively correlated with ADHD. These pairwise correlations among disorders were correlated with the corresponding pairwise correlations among disorders derived from genomewide association studies (r = 0.494). Our results show substantial similarities in sMRI phenotypes among neuropsychiatric disorders and suggest that these similarities are accounted for, in part, by corresponding similarities in common genetic variant architectures.

Highlights

Neuropsychiatric disorders have substantial heritability, as shown by many studies of twins and families [1]
Summary statistics from Enhancing Neuroimaging Genetics through MetaAnalysis (ENIGMA) structural neuroimaging studies were collected from 12 multisite analyses published by the ENIGMA Consortium for the following neuropsychiatric disorders: attention-deficit/hyperactivity disorder (ADHD) [10, 11], autism spectrum disorder (ASD) [12], bipolar disorder (BD) [13, 14], epilepsy [15], major depressive disorder (MDD) [16, 17], obsessive compulsive disorder (OCD) [18, 19], and SCZ [20, 21]
Prior to computing the summary statistics, the regional brain volumes had been segmented with a common ENIGMA protocol using FreeSurfer software

Summary

Introduction

Neuropsychiatric disorders have substantial heritability, as shown by many studies of twins and families [1]. Genomewide association studies (GWAS) have shown that common genetic variants account for some of this heritability, and that some of this heritability is shared across neuropsychiatric disorders [2,3,4,5]. The genetic overlap across disorders may partly explain why these disorders tend to cooccur with one another in both clinical and community samples [6]

Results

Discussion

Conclusion