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Examining the heritability of functional brain networks in adolescence

Coffman, C.; Koirala, S.; Hermosillo, R.; Lundquist, J.; Grimsurd, G.; Miranda Dominguez, O.; Weldon, K. B.; Anderson, M.; Madison, T.; Nelson, S.; Elison, J. T.; Wilson, S.; Fair, D.; Tervo-Clemmens, B.; Basu, S.; Feczko, E. J.

2025-08-10 genomics
10.1101/2025.08.08.669358 bioRxiv
Show abstract

Discovering mechanisms underlying mental illness requires disentangling genetic and environmental factors influencing mental health. Researchers have started investigating the brains role as a potential intermediate biomarker linking genes and environment to mental health; however, understanding how much genetics shapes adolescent brain function remains elusive. Using data from the ABCD study (5,247 unrelated, 330 dizygotic, 248 monozygotic twin subjects), we estimated the heritability of functional connectivity and topography using both SNP and twin data. SNP-based heritability was calculated using genetic correlation and the recently developed AdjHE-RE estimator. We found low SNP heritability for brain functional connectivity (median = 2e-10% Gordon, 5.8e-7% probabilistic) and topography (max = 2%). Twin estimates using ACE models replicated prior findings from the literature (median = 8.9e-6% Gordon, 6% probabilistic, 27% topography). This suggest that additive genetic effects are minimally associated with functional brain features in adolescents highlighting the importance of considering both genetic and environmental factors when studying the development of functional brain networks and their relevance to mental health.

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