The Genetics of Structural Similarity Networks in the Brain

COEX 

Recent imaging-genetics research has demonstrated that heritable MRI-derived brain structural features show important genetic overlaps with brain function and psychopathology [1,2,3]. Yet, while the brain forms a genetically-coordinated network, existing work on the genetics of brain structure has focused on structural features at the global or regional level. As such, the genetics of network-based measures of brain structure remain largely unknown.

In this work, we conducted hundreds of genome-wide association studies (GWAS) to comprehensively characterize the genetics of structural similarity networks in the brain. Specifically, using N>30,000 subjects from the UK Biobank, we studied the genetics of Morphometric INverse Divergence (MIND), a robust and biologically-validated method to construct structural similarity networks from MRI [4]. We identified 109 independent genomic regions associated with MIND, many of which were not associated with the structural feature from which the networks were derived.

We observed positive genetic correlations between MIND network edges and the corresponding edges from functional connectivity (FC) networks, offering new evidence for a shared genetic basis for brain structure and function. Moreover, we identified putative causal relationships between MIND and functional connectivity that were specific to the association cortex.

Finally, we observed evidence for local genetic correlations between MIND network connectivity and schizophrenia, identifying specific genes such as CACNA1c that may disproportionately contribute to the shared genetic basis of brain connectivity and mental illness.