Heritability of fractional anisotropy in human white matter: A comparison of Human Connectome Project and ENIGMA-DTI data

Abstract

The degree to which genetic factors influence brain connectivity is beginning to be understood. Large-scale efforts are underway to map the profile of genetic effects in various brain regions. The NIH-funded Human Connectome Project (HCP) is providing data valuable for analyzing the degree of genetic influence underlying brain connectivity revealed by state-of-the-art neuroimaging methods. We calculated the heritability of the fractional anisotropy (FA) measure derived from diffusion tensor imaging (DTI) reconstruction in 481 HCP subjects (194/287 M/F) consisting of 57/60 pairs of mono- and dizygotic twins, and 246 siblings. FA measurements were derived using (Enhancing NeuroImaging Genetics through Meta-Analysis) ENIGMA DTI protocols and heritability estimates were calculated using the SOLAR-Eclipse imaging genetic analysis package. We compared heritability estimates derived from HCP data to those publicly available through the ENIGMA-DTI consortium, which were pooled together from five-family based studies across the US, Europe, and Australia. FA measurements from the HCP cohort for eleven major white matter tracts were highly heritable (h2=0.53–0.90, p<10−5), and were significantly correlated with the joint-analytical estimates from the ENIGMA cohort on the tract and voxel-wise levels. The similarity in regional heritability suggests that the additive genetic contribution to white matter microstructure is consistent across populations and imaging acquisition parameters. It also suggests the overarching genetic influence provides an opportunity to define a common genetic search space for future gene-discovery studies. Uniquely, the measurements of additive genetic contribution performed in this study can be repeated using online genetic analysis tools provided by the HCP ConnectomeDB web application.

Reproducibility of quantitative structural and physiological MRI measurements

“…However, these conditions are unlikely to be maintained throughout the life of longer longitudinal or cross‐sectional studies where scanner upgrades, significant hardware changes such as changes head coil, and other methodological changes may be expected. To address these aspects of longitudinal studies, our group and others used two strategies to accommodate for methodological changes: collections of calibration data and use of meta‐ and mega‐analyses (Jahanshad et al., 2013; Kochunov et al., 2015; McGuire et al., 2014a). In the first approach, calibration data are collected before and after change to derive cross‐calibration parameters.…”

“…Alternatively, cross‐sectional and longitudinal studies with short interimaging periods can use statistical aggregation approaches that treat samples collected on different hardware as independent datasets. ENIGMA consortium has demonstrated the utility in meta‐ and mega‐analysis of quantitative neuroimaging data (Jahanshad et al., 2013; Kochunov et al., 2015). …”

Imaging structural and functional brain development in early childhood

“…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.…”

White Matter Microstructure and Subcortical Gray Matter Structure Volumes in Aspartylglucosaminuria; a 5-Year Follow-up Brain MRI Study of an Adolescent with Aspartylglucosaminuria and His Healthy Twin Brother

“…This is a preliminary study with only one patient, which is obviously the major limitation of the study. However, FA measurements in the large Human Connectome Project are highly hereditable in major WM tracts (Kochunov et al 2015). Also, in a prior DTI study on twins, it was noted that WM hereditability is markedly high in adolescent males (Chiang et al 2011), which makes the twin brother in our study an especially suitable control person.…”