Heritability of white matter microstructure in late middle age: A twin study of tract‐based fractional anisotropy and absolute diffusivity indices

Vuoksimaa, Eero; Panizzon, Matthew S.; Hagler, Donald J.; Hatton, Sean N.; Fennema-Notestine, Christine; Rinker, Daniel A.; Eyler, Lisa T.; Franz, Carol E.; Lyons, Michael J.; Neale, Michael C.; Tsuang, Ming T.; Dale, Anders M.; Kremen, William S.

doi:10.1002/hbm.23502

Cited by 51 publications

(50 citation statements)

References 59 publications

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“…We sought to clarify whether the same or different genetic and environmental factors contribute to AD and RD. We report that AD and RD exhibit significant heritability estimates of generally similar magnitude in most of the bilateral tracts measured, consistent with our prior report of diffusivity heritability estimates separately for left and right hemispheres (Vuoksimaa et al, ). The core novel finding is that there are strong genetic correlations between AD and RD in the majority of tracts measured.…”

Section: Discussionsupporting

confidence: 91%

“… The mean diffusion measures of these fiber tracts by hemisphere for this cohort have previously been characterized (refer to table in Vuoksimaa et al, ).…”

Section: Resultsmentioning

confidence: 99%

“…In contrast, this study suggested that AD is more influenced by environmental factors. Recently, our group (Vuoksimaa et al, ) reported on the heritability of diffusivity measures in middle‐aged male twins as part of the ongoing Vietnam Era Twin Study of Aging (VETSA; Kremen, Franz, & Lyons, ; Kremen et al, ). We showed that despite the narrow age range of these nondemented, community‐dwelling individuals age was correlated with the global average for each diffusion index measured (FA, AD, RD, and MD), and older age was related to poorer white matter microstructural properties even in middle age (Vuoksimaa et al, ).…”

Section: Introductionmentioning

confidence: 99%

“…Recently, our group (Vuoksimaa et al, ) reported on the heritability of diffusivity measures in middle‐aged male twins as part of the ongoing Vietnam Era Twin Study of Aging (VETSA; Kremen, Franz, & Lyons, ; Kremen et al, ). We showed that despite the narrow age range of these nondemented, community‐dwelling individuals age was correlated with the global average for each diffusion index measured (FA, AD, RD, and MD), and older age was related to poorer white matter microstructural properties even in middle age (Vuoksimaa et al, ). Contrary to the observations of Kochunov et al (), most tracts measured were significantly heritable for both RD ( a 2 = .74 for all tracts combined) and AD ( a 2 = .72 for all tracts combined) similar to findings in neonate (Lee et al, ) and pediatric twins (Brouwer et al, ).…”

Section: Introductionmentioning

confidence: 99%

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Genetic relatedness of axial and radial diffusivity indices of cerebral white matter microstructure in late middle age

Hatton

Panizzon

Vuoksimaa

et al. 2018

Human Brain Mapping

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Two basic neuroimaging-based characterizations of white matter tracts are the magnitude of water diffusion along the principal tract orientation (axial diffusivity, AD) and water diffusion perpendicular to the principal orientation (radial diffusivity, RD). It is generally accepted that decreases in AD reflect disorganization, damage, or loss of axons, whereas increases in RD are indicative of disruptions to the myelin sheath. Previous reports have detailed the heritability of individual AD and RD measures, but have not examined the extent to which the same or different genetic or environmental factors influence these two phenotypes (except for corpus callosum). We implemented bivariate twin analyses to examine the shared and independent genetic influences on AD and RD. In the Vietnam Era Twin Study of Aging, 393 men (mean age = 61.8 years, SD = 2.6) underwent diffusion-weighted magnetic resonance imaging. We derived fractional anisotropy (FA), mean diffusivity (MD), AD, and RD estimates for 11 major bilateral white matter tracts and the mid-hemispheric corpus callosum, forceps major, and forceps minor. Separately, AD and RD were each highly heritable. In about three-quarters of the tracts, genetic correlations between AD and RD were >.50 (median = .67) and showed both unique and common variance. Genetic variance of FA and MD were predominately explained by RD over AD. These findings are important for informing genetic association studies of axonal coherence/damage and myelination/demyelination. Thus, genetic studies would benefit from examining the shared and unique contributions of AD and RD.

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Section: Discussionsupporting

confidence: 91%

“… The mean diffusion measures of these fiber tracts by hemisphere for this cohort have previously been characterized (refer to table in Vuoksimaa et al, ).…”

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Genetic relatedness of axial and radial diffusivity indices of cerebral white matter microstructure in late middle age

Hatton

Panizzon

Vuoksimaa

et al. 2018

Human Brain Mapping

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“…Together with the adult data, these results suggest that the heritability of white-matter volume is stable over the course of postnatal brain development and that the heritability of grey-matter volume seems to increase during the period of rapid grey-matter growth from birth to later childhood. Diffusion-tensor imaging studies also indicate that white-matter microstructure, as represented by FA, is generally highly heritable in adults, with variability across different white-matter tracts 147, 148 . By comparison, the heritability of tract-based FA in neonates 149, 150 and in 9- and 12-year-olds 151 is relatively low, suggesting that the heritability of white-matter microstructure increases over the course of childhood; however, longitudinal studies are lacking.…”

Section: Influences Of Genes and Environmentmentioning

confidence: 99%

Imaging structural and functional brain development in early childhood

2018

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In humans, the period from term birth to ~2 years of age is characterized by rapid and dynamic brain development and plays an important role in cognitive development and risk for disorders such as autism and schizophrenia. Recent imaging studies have begun to delineate the growth trajectories of brain structure and function in the first years after birth and their relationship to cognition and risk for neuropsychiatric disorders. This Review discusses the development of grey and white matter, structural and functional networks, as well as genetic and environmental influences on early childhood brain development. We also discuss initial evidence regarding the usefulness of early imaging biomarkers for predicting cognitive outcomes and risk for neuropsychiatric disorders.

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Heritability of abnormalities in limbic networks of autism spectrum disorder children: Evidence from an autism spectrum disorder twin study

et al. 2022

Autism Research

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Although the limbic system is closely related to emotion and social behaviors, little is known about the integrity of limbic pathways and how genetics influence the anatomical abnormalities of limbic networks in children with autism spectrum disorder (ASD). Therefore, we used an ASD twin study design to evaluate the microstructural integrity and autism-related differences in limbic pathways of young children with ASD and to estimate the heritability of limbic tracts microstructure variance. We obtained diffusion tensor imaging scans from 33 pairs of twins with ASD aged 2-9 years and 20 age-matched typically developing children. The ACE model was used to estimate the relative effects of additive genetic factors (A), shared environmental factors (C) and specific environmental factors (E) on the variability of diffusivity measurements. We found a significant decrease in fractional anisotropy (FA) in the bilateral fornix and uncinate fasciculus (UF), as well as increased mean diffusivity (MD) and radial diffusivity (RD) in the bilateral fornix and right UF of ASD children. Correlation analysis showed that FA, MD, and lateralization indices of UF were correlated with autism diagnostic observation schedule scores. The ACE model revealed that genetic effects may drive some of the variability of microstructure in the bilateral fornix, cingulum, and left UF. In conclusion, in children with ASD, there are abnormalities in the white matter microstructure of the limbic system, which is related to the core symptoms; these abnormalities may be related to the relative contribution of genetic and environmental effects on specific tracts. Lay SummaryAutism spectrum disorder (ASD) children have abnormal white matter structure in limbic system related to ASD symptoms, and genetic factors play an important role in the development of limbic tracts.

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Heritability of white matter microstructure in late middle age: A twin study of tract‐based fractional anisotropy and absolute diffusivity indices

Cited by 51 publications

References 59 publications

Genetic relatedness of axial and radial diffusivity indices of cerebral white matter microstructure in late middle age

Genetic relatedness of axial and radial diffusivity indices of cerebral white matter microstructure in late middle age

Imaging structural and functional brain development in early childhood

Heritability of abnormalities in limbic networks of autism spectrum disorder children: Evidence from an autism spectrum disorder twin study

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