Inferring the heritability of large-scale functional networks with a multivariate ACE modeling approach

Recent evidence suggests that the human functional connectome is stable at different timescales and is unique. These characteristics posit the functional connectome not only as an individual marker but also as a powerful discriminatory measure characterized by high intersubject variability. Among distinct sources of intersubject variability, the long-term sources include functional patterns that emerge from genetic factors. Here, we sought to investigate the contribution of additive genetic factors to the variability of functional networks by determining the heritability of the connectivity strength in a multivariate fashion. First, we reproduced and extended the connectome fingerprinting analysis to the identification of twin pairs. Then, we estimated the heritability of functional networks by a multivariate ACE modeling approach with bootstrapping. Twin pairs were identified above chance level using connectome fingerprinting, with monozygotic twin identification accuracy equal to 57.2% on average for whole-brain connectome. Additionally, we found that a visual (0.37), the medial frontal (0.31), and the motor (0.30) functional networks were the most influenced by additive genetic factors. Our findings suggest that genetic factors not only partially determine intersubject variability of the functional connectome, such that twins can be identified using connectome fingerprinting, but also differentially influence connectivity strength in large-scale functional networks. AUTHOR SUMMARY The functional connectome is a unique representation of the functional organization of the human brain. As such, it has been extensively used as an individual marker, a "fingerprint," because of its high intersubject variability. Here, we sought to investigate the influence of genetic factors on intersubject variability of functional networks. Therefore, we extended the connectome fingerprinting analysis to the identification of twin pairs, and we estimated the heritability of functional networks by a multivariate ACE modeling approach with bootstrapping. We found that genetic factors not only partially determine intersubject variability of the functional connectome, such that monozygotic twin identification accuracy achieved 57.2% on average using whole-brain connectome in the fingerprinting analysis, but also differentially influence connectivity strength in large-scale functional networks.