Introduction: White matter hyperintensities (WMH) indicate white matter brain lesions
in magnetic resonance imaging (MRI), which can be used as a marker for brain aging
and cerebrovascular and neurodegenerative disorders. Twin studies revealed substantial
but not uniform WMH heritability in elderly twins. The objective of our study was
to investigate the genetic and environmental components of WMH, as well as their importance
in a healthy twin population, utilizing 3T MRI scanners in a middle-aged twin population.
Methods: Brain MRI was performed on 120 healthy adult twins from the Hungarian Twin
Registry on a 3T scanner (86 monozygotic, MZ and 34 dizygotic, DZ twins; median age
50 ± 26.5 years, 72.5% female and 27.5% male). The count of WMH on FLAIR images was
calculated using an automated volumetry pipeline (volBrain) and human processing.
The age- and sex-adjusted MZ and DZ intra-pair correlations were determined and the
total variance was decomposed into genetic, shared and unique environmental components
using structural equation modeling. Results: Age and sex-adjusted MZ intrapair correlations
were higher than DZ correlations, indicating moderate genetic influence in each lesion
(rMZ = 0.466, rDZ = -0.025 for total count; rMZ = 0.482, rDZ = 0.093 for deep white
matter count; rMZ = 0.739, rDZ = 0.39 for infratentorial count; rMZ = 0.573, rDZ =
0.372 for cerebellar count and rMZ = 0.473, rDZ = 0.19 for periventricular count),
indicating a moderate heritability (A = 40.3%, A = 45%, A = 72.7% and A = 55.5%and
47.2%, respectively). The rest of the variance was influenced by unique environmental
effects (E between 27.3% and 59.7%, respectively). Conclusions: The number of WMH
lesions is moderately influenced by genetic effects, particularly in the infratentorial
region in middle-aged twins. These results suggest that the distribution of WMH in
various brain regions is heterogeneous.
