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

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

Genetic and environmental effects on the development of white matter hyperintensities in a middle age twin population

Introduction: White matter hyperintensities (WMH) are indicative of white matter brain lesions in the magnetic resonance imaging (MRI), which can be used as a marker for brain aging, 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). The count of WMH on FLAIR images was calculated using both an automated volumetry pipeline (volBrain) and human processing. The age- and sexadjusted 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 lesions (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

Heritability of Subcortical Grey Matter Structures

Introduction: Subcortical grey matter structures play essential roles in cognitive, affective, social, and motoric functions in humans. Their volume changes with age and decreased volumes have been linked with many neuropsychiatric disorders. The aim of our study was to examine the heritability of six subcortical brain volumes; the amygdala, caudate nucleus, pallidum, putamen, thalamus, and nucleus accumbens, and four general brain volumes; total intracranial volume, grey matter, white matter, and cerebrospinal fluid (CSF) volume in twins. Materials and Methods: 120 healthy adult twins from the Hungarian Twin Registry (86 monozygotic and 34 dizygotic; median age 50±26.5 years) underwent brain magnetic resonance imaging. Two volumetry pipelines, Computational Anatomy Toolbox 12 (CAT12) and volBrain were used to calculate subcortical and general brain volumes from three-dimensional T1-weighted images. Age- and sex-adjusted monozygotic and dizygotic intra-pair correlations were calculated and the univariate ACE model was applied. Pearson’s correlation test was used to compare the results obtained by the two pipelines. Results: Age- and sex-adjusted heritability estimates for the four general brain volumes were 0.78- 0.93 and 0.89-0.94 using CAT12 and volBrain, respectively. Heritability estimates, using CAT12 for the amygdala, caudate nucleus, pallidum, putamen, and nucleus accumbens were between 0.76- 0.95. The thalamus volume was more strongly influenced by common environmental factors (C=0.49-0.74). Heritability estimates, using volBrain were between 0.73-0.92 for the nucleus accumbens, pallidum, putamen, right amygdala and right caudate. The left caudate, left amygdala and thalamus were more strongly influenced by common environmental factors (C=0.49-0.86). A strong correlation between CAT12 and volBrain (r=0.74-0.94) was obtained for all volumes. Conclusions: The majority of examined subcortical volumes appeared strongly heritable. The thalamus was more strongly influenced by common environmental factors. Our results underline the importance of identifying relevant genes responsible for the variation in subcortical structure volume and associated diseases

Heritability of Subcortical Grey Matter Structures

Background and Objectives: Subcortical grey matter structures play essential roles in cognitive, affective, social, and motoric functions in humans. Their volume changes with age, and decreased volumes have been linked with many neuropsychiatric disorders. The aim of our study was to examine the heritability of six subcortical brain volumes (the amygdala, caudate nucleus, pallidum, putamen, thalamus, and nucleus accumbens) and four general brain volumes (the total intra-cranial volume and the grey matter, white matter, and cerebrospinal fluid (CSF) volume) in twins. Materials and Methods: A total of 118 healthy adult twins from the Hungarian Twin Registry (86 monozygotic and 32 dizygotic; median age 50 ± 27 years) underwent brain magnetic resonance imaging. Two automated volumetry pipelines, Computational Anatomy Toolbox 12 (CAT12) and volBrain, were used to calculate the subcortical and general brain volumes from three-dimensional T1-weighted images. Age- and sex-adjusted monozygotic and dizygotic intra-pair correlations were calculated, and the univariate ACE model was applied. Pearson’s correlation test was used to compare the results obtained by the two pipelines. Results: The age- and sex-adjusted heritability estimates, using CAT12 for the amygdala, caudate nucleus, pallidum, putamen, and nucleus accumbens, were between 0.75 and 0.95. The thalamus volume was more strongly influenced by common environmental factors (C = 0.45−0.73). The heritability estimates, using volBrain, were between 0.69 and 0.92 for the nucleus accumbens, pallidum, putamen, right amygdala, and caudate nucleus. The left amygdala and thalamus were more strongly influenced by common environmental factors (C = 0.72−0.85). A strong correlation between CAT12 and volBrain (r = 0.74−0.94) was obtained for all volumes. Conclusions: The majority of examined subcortical volumes appeared to be strongly heritable. The thalamus was more strongly influenced by common environmental factors when investigated with both segmentation methods. Our results underline the importance of identifying the relevant genes responsible for variations in the subcortical structure volume and associated diseases