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BRIEF RESEARCH REPORT article

Front. Hum. Neurosci.

Sec. Brain Imaging and Stimulation

Genetic and environmental influence on white matter: Insight from an Italian twin population study

Provisionally accepted
Giovanni VidettaGiovanni Videtta1Chiara ColliChiara Colli1,2*Letizia SquarcinaLetizia Squarcina2Corrado FagnaniCorrado Fagnani3Emanuela MeddaEmanuela Medda3Cristina D'IppolitoCristina D'Ippolito3Carolina BoniventoCarolina Bonivento4Maria NobileMaria Nobile5Paolo BrambillaPaolo Brambilla1,2
  • 1Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
  • 2Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
  • 3Istituto Superiore di Sanita, Rome, Italy
  • 4Scientific Institute IRCCS Eugenio Medea, Pasian di Prato (Udine), Italy
  • 5Istituto di Ricovero e Cura a Carattere Scientifico Eugenio Medea, Bosisio Parini, Italy

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Introduction. The heritability of white matter (WM) has been a central focus of diffusion neuroimaging and genetic research. Twin studies have reported high heritability estimates for WM integrity, primarily based on fractional anisotropy (FA). However, other diffusion tensor imaging (DTI) metrics - mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) - remain less explored. Methods. In the present twin study, we assessed WM heritability using FA, MD, AD, and RD metrics. Tract-Based Spatial Statistics was applied to DTI data from 81 healthy twin pairs (33 monozygotic, 48 dizygotic) recruited through the population-based Italian Twin Registry. Twin correlations and genetic and environmental variance components were estimated for each DTI index across brain regions. Results. Monozygotic twins exhibited higher correlations than dizygotic twins across most brain regions; however, a few regions showed an unexpected inverse pattern. Notably, while several regions demonstrated strong genetic influences, others showed no detectable genetic contribution, suggesting a substantial role for environmental factors in shaping WM characteristics in those areas. Conclusion. These findings revealed regional variability in WM heritability and challenged the assumption of uniform genetic influence, highlighting the importance of considering early environmental factors and supporting the development of more nuanced models of WM development.

Keywords: Diffusion Tensor Imaging, Genetics, heritability, tract-based spatial statistics, Twins, white matter

Received: 10 Dec 2025; Accepted: 13 Feb 2026.

Copyright: © 2026 Videtta, Colli, Squarcina, Fagnani, Medda, D'Ippolito, Bonivento, Nobile and Brambilla. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Chiara Colli

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Supplementary Material