Human Connectomes are Heritable.
Jaewon ChungEric W BridgefordMichael PowellJoshua T VogelsteinPublished in: bioRxiv : the preprint server for biology (2023)
The heritability of human connectomes is crucial for understanding the influence of genetic and environmental factors on variations in connectomes, and their implications for behavior and disease. However, current methods for studying heritability assume an associational rather than a causal effect, and rely on modeling assumptions that may not be appropriate for complex, high-dimensional connectomes. To address these limitations, we propose two solutions: first, formalize heritability as causal effects, and identify measurable covariates to control for unmeasured confounding, allowing us to make causal claims. Second, leverage statistical models that capture the underlying structure and dependence within connectomes, enabling us to define different notions of connectome heritability. For example, we remove common structures with increasing complexity across connectomes and test whether heritability exists beyond these commonalities. We then develop a non-parametric test to detect causal heritability and apply it to connectomes estimated from the Human Connectome Project diffusion data. Our investigation provides compelling evidence that genetics play a significant role in shaping connectomes.