Genetic and Environmental Influence on the Human Functional Connectome

Area of Science:

• Neuroscience
• Behavioral Genetics
• Psychiatric Genetics

Background:

• Understanding the genetic and environmental underpinnings of the human brain's functional connectome is vital for bridging the gap between genetic predispositions and clinical outcomes or cognitive functions.
• Previous research has explored genetic influences on brain structure and function, but high-resolution mapping of genetic effects across the entire functional connectome remains an area for deeper investigation.

Purpose of the Study:

• To comprehensively map genetic and environmental influences on pairwise functional connections within the human brain's resting-state functional magnetic resonance imaging (rs-fMRI) connectome.
• To identify specific functional connections with significant genetic heritability and explore the distinctiveness of these genetic influences compared to global connectivity measures and motion artifacts.

Main Methods:

• Analysis of rs-fMRI data from two independent adult twin samples (N=446 and N=371) to assess genetic and environmental contributions to approximately 35,000 pairwise functional connections across 264 brain regions.
• Application of a novel connectome-wide bivariate genetic modeling approach to differentiate genetic influences on individual connections from global connectivity, network properties, and head motion during scanning.
• Quantification of heritability estimates and nonshared/shared environmental influences for each functional connection.

Main Results:

• Nonshared environmental influences were predominant across the entire functional connectome.
• Approximately 14-22% of functional connections showed nominally significant genetic influence in each sample, with 4.6% significant in both, and 1-2% exhibiting heritability exceeding 30%.
• Genetic influences on specific connections were found to be distinct from those affecting global connectivity measures, network-based connectivity estimates, and movement parameters.

Conclusions:

• The brain's genetic architecture of functional connectivity is highly diverse, with localized genetic effects that are not easily predicted from lower-resolution or structural data alone.
• A high-resolution genetic taxonomy of brain connectivity reveals specific pathways influenced by genetics, which can serve as valuable intermediate phenotypes for understanding the genetic basis of brain disorders.
• Future research can leverage this detailed genetic mapping to investigate the etiological pathways of neurological and psychiatric conditions.