Heritability of complex white matter diffusion traits assessed in a population isolate

Area of Science:

• Neuroimaging genetics
• Brain microstructure heritability
• Diffusion-weighted imaging (DWI) analysis

Background:

• Diffusion-weighted imaging (DWI) noninvasively assesses cerebral microstructure by analyzing water diffusion patterns and directions.
• Understanding the genetic contribution to diffusion signals across white matter (WM) and gray matter (GM) is crucial for brain research.

Purpose of the Study:

• To calculate the heritability of DWI parameters in cerebral WM and GM.
• To investigate the genetic contribution to diffusion signals using advanced DWI models.
• To compare heritability estimates across different DWI modeling approaches.

Main Methods:

• Utilized the Old Order Amish (OOA) population isolate for its large family pedigrees and environmental homogeneity.
• Compared heritability of measures from diffusion tensor imaging (DTI), permeability-diffusivity (PD) model, and neurite orientation dispersion and density imaging (NODDI) model.
• Targeted diffusion signal modeling in the corpus callosum WM and cingulate gyrus GM using one, two, and three diffusion compartments.

Main Results:

• Replicated high heritability for DTI-based fractional anisotropy (h²=0.67) and radial diffusivity (h²=0.72) in WM.
• Observed high heritability for the PD model's permeability-diffusivity index (h²=0.64 WM, h²=0.84 GM) and NODDI's neurite density (h²=0.70 WM, h²=0.55 GM).
• Found the NODDI model's orientation dispersion index significantly heritable only in GM (h²=0.68).

Conclusions:

• DWI measures derived from multicompartmental models demonstrate significant heritability in both WM and GM.
• DWI provides valuable phenotypes for genetic research into brain structure and function.
• Identified genes may elucidate mechanisms underlying neurological and mental disorders associated with diffusion imaging anomalies.