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The Shared Genetic Basis of Neuropsychiatric Disorders

A recent study has demonstrated that there are substantial similarities in the structural phenotypes of different neuropsychiatric disorders. Furthermore, they report that these structural similarities are, in part, explained by genetics.

The Genetic Basis of Neuropsychiatric Disorders

Family and twin studies have demonstrated that many neuropsychiatric disorders have significant levels of heritability. Furthermore, genome-wide association studies (GWAS) have identified common genetic variants which contribute to this heritability. Importantly, many of these same genetic variants are shared across several neuropsychiatric disorders. This genetic overlap may explain why many disorders tend to co-occur with one another.

Structural Differences in Neuropsychiatric Disorders

Much less is known about the degree to which structural brain abnormalities are shared among disorders, and if so, the degree to which these similarities have a genetic basis. Subcortical brain volume and cortical thickness/surface area changes dynamically through our lives, impacted by genetic and environmental factors.

Brain volumes can be measured using structural magnetic resonance imaging (sMRI) and certain sMRI phenotypes have been linked to different neuropsychiatric disorders. This study aimed to estimate the degree of similarity in sMRI phenotypes among these disorders and evaluate whether these similarities are influenced by genetic correlations.

Neurological and Genetic Correlations

The study reported that certain disorders were linked to specific sMRI phenotypes. However, in some cases, these sMRI phenotypes were similar to one another, suggesting that changes in specific brain regions plays a role in several different disorders. These neuroanatomical similarities were also correlated to a shared genetic basis.

The shared role of specific brain regions and corresponding genetic loci is intriguing. These findings suggest that to varying degrees, different neuropsychiatric disorders share aspects of their aetiology and pathophysiology. This is supported by previous findings.

Supporting Evidence

Schizophrenia and Bipolar Disorder were found to have high levels of overlap in sMRI phenotypes. Previous studies have also reported a significant aetiologic overlap between the two disorders, supporting these findings. Both disorders also showed strong sMRI phenotype correlations with Major Depressive Disorder and OCD. This aligns with previous findings of OCD as a common comorbidity of Schizophrenia.

Overall, the researchers found a modest, yet distinct linear correlation between sMRI phenotypes and genetic correlations. However, only ~24% of this variation cold be accounted for by genetic correlations. Combined, these findings suggest that more work is needed to examine the shared pathophysiologic features between these disorders, while taking genetic, neuroanatomic, and environmental factors into consideration.

Final Remarks

The study reported substantial cross-disorder correlations in selective brain region vulnerability. These correlations were also positively associated with genetic factors. Several disorders with separate diagnostic classification showed significant overlap in aetiology and pathophysiology. Further studies are required to understand the shared role of sMRI abnormalities and genetics in the progression of neuropsychiatric disorders.

Image Credit: Pixabay

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Gene / Genetic Variants / GWAS