Genetic and Environmental Effects on the Development of White Matter Hyperintensities in a Middle Age Twin Population

Abstract

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.

Keywords: MRI; heritability; twins; volBrain; white matter hyperintensities.

Figure 1

FLAIR MRI imaging of 65 years old female monozygotic twins (left column); the right side column pictures are the segmented version of the FLAIR images. The similarity of the anatomy and WMH of the cut is visible. According to our analysis, one twin has a total number of 17 WMHs (first row) and the other pair has a total number of 19 WMHs (second row). The red color represents the periventricular WMH and the blue and green colors represent the juxtacortical and deep white matter WMH—image from the Semmelweis University Medical Imaging Centre.

Figure 2

FLAIR MRI imaging of 69 years old female dizygotic twins (left column); the right side column pictures show the segmented version of the FLAIR images. The difference in the anatomy and number of WMH of the cut is visible in this image. According to our analysis, one twin has a total number of 24 WMHs (first row) and the other pair has a total number of 33 WMHs (second row). The red color represents the periventricular WMH and the blue color represents the juxtacortical WMH—image from the Semmelweis University Medical Imaging Centre.