The Genetic and Environmental Architecture of the Human Functional Connectome

TL;DR

This study extends twin models to analyze genetic and environmental influences on the human functional connectome, accounting for measurement error, and reveals structured, multiscale brain networks affected by these factors.

Contribution

It introduces a method to incorporate measurement error into twin models for functional connectivity, enabling more accurate analysis of genetic and environmental effects.

Findings

Genetic and environmental influences form distinct, hierarchical brain network modules.

Measurement error correction improves the interpretability of twin model analyses.

Functional couplings show differentiated influences across conditions and scales.

Abstract

Functional connectivity varies across individuals due to genetic and environmental factors, yet classical twin models typically confound non-shared environment with measurement error and are largely limited to resting-state analyses. We hypothesized that: i) explicitly modeling measurement error from repeated fMRI sessions enables more accurate application of classical twin models (ACE/ADE) to functional connectivity; ii) model applicability depends on scan-length and parcellation granularity; iii) genetic and environmental effects on functional connectomes show differentiated functional modules across conditions. We extended ACE/ADE models to include a repeated-scan derived error term by analyzing monozygotic and dizygotic twins from the Young-Adult Human Connectome Project dataset. Genetic and environment variance components were estimated for all functional couplings across resting-state and task conditions, integrated across conditions using a minimum-error criterion, and analyzed using multilayer community detection across resolution scales. Functional couplings segregated into distinct categories characterized by shared environmental, additive, dominant, or epistatic influences, with a substantial fraction not meeting twin-model assumptions. Integrating across conditions revealed hierarchical community structure in genetic and environmental components observed across community resolution scales. Incorporating measurement error into twin models improves interpretability and applicability at the functional connectome level, revealing that genetic and environmental influences are structured into coherent, multiscale brain networks.