Genetic influences on resting‐state functional networks: A twin study

Abstract

Alterations in resting-state networks (RSNs) are often associated with psychiatric and neurologic disorders. Given this critical linkage, it has been hypothesized that RSNs can potentially be used as endophenotypes for brain diseases. To validate this notion, a critical step is to show that RSNs exhibit heritability. However, the investigation of the genetic basis of RSNs has only been attempted in the default-mode network at the region-of-interest level, while the genetic control on other RSNs has not been determined yet. Here we examined the genetic and environmental influences on eight well-characterized RSNs by using a twin design. Resting-state functional magnetic resonance imaging data in 56 pairs of twins were collected. The genetic and environmental effects on each RSN were estimated by fitting the functional connectivity covariance of each voxel in the RSN to the classic ACE twin model. The data showed that although environmental effects accounted for the majority of variance in widespread areas, there were specific brain sites that showed significant genetic control for individual RSNs. These results suggest that part of the human brain functional connectome is shaped by genomic constraints. Importantly, this information can be useful for bridging genetic analysis and network-level assessment of brain disorders.

Environmental factors linked to depression vulnerability are associated with altered cerebellar resting-state synchronization

“…Both cerebellar resting-state connectivity and depression liability, when considered independently, are caused by the confluence of many genetic and environmental factors131415. Although disengaging genes and environment has a prominent value in psychiatric research16, whether the association between cerebellar functionality and depression vulnerability can be explained by genetic or non-genetic factors remains largely unexplored.…”

“…First, it has been proposed that some alternative phenotypes (i.e., endophenotypes) would have a tougher connection with the genetic basis of psychopathology than phenomenologically-derived clinical diagnoses1718. As some resting-state networks including cerebellar regions are likely to serve as endophenotypes in brain research13, it is feasible hypothesizing that some genetic factors determining cerebellar resting-state activity may also modify the risk for depression. Secondly, the link between the cerebellum and depression liability may perhaps be due to environmental factors.…”

“…While the presence of resting-state fMRI alterations at cerebral regions –i.e., the default mode network– is broadly acknowledged in depressive disorders, the contribution of cerebellar function to those clinical phenotypes has recently been gaining attention9. This is a relevant point since data on healthy twins and families shows significant quantitative genetic components of whole-brain resting-state fMRI activity at cerebellar regions1314, but their putative modulation of depression vulnerability remains only scarcely explored.…”

“…As co-twins of a MZ pair have almost identical DNA sequences, their phenotypic similarities and differences were investigated to gain insights on putative familial and environmental influences. Following conventions from classical quantitative genetic analysis, intrapair brain differences in genetically identical individuals (MZ twins) are considered a measure of environmental factors influencing that neural phenotype1330. Since the cerebellar fMRI signal constitutes a well-defined resting-state network33, and considering that intra-cerebellar resting-state connectivity may be especially relevant in neuropsychiatry34, an anatomically-restricted 26-node network comprising different subdivisions of the cerebellum was examined.…”

Relationship of a common OXTR gene variant to brain structure and default mode network function in healthy humans

“…The rsFC of the DMN has been implicated in social cognition (Andrews-Hanna, 2012), so its disruption may be relevant to the manifestation of symptoms in these disorders. fMRI signal synchronicity among DMN regions is moderately heritable (Fu et al, 2015; Glahn et al, 2010), but so far, specific genetic variants that explain DMN synchronicity are unknown.…”