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Area of Science:

  • Neurogenetics
  • Brain Imaging
  • Aging Research

Background:

  • The genetic underpinnings of white matter hyperintensities (WMH) remain largely unexplored.
  • Understanding the heritability of WMH is crucial for elucidating its pathogenesis.

Purpose of the Study:

  • To investigate the heritability of WMH across different brain regions and sexes.
  • To examine the influence of aging on WMH heritability.

Main Methods:

  • Utilized a twin design from the Older Australian Twins Study (n=320).
  • Estimated heritability using magnetic resonance imaging (MRI) and medical assessments.
  • Calculated heritability as the ratio of additive genetic variance to total phenotypic variance.

Main Results:

  • High heritability for total WMH volume (0.76), periventricular WMH (0.64), and deep WMH (0.77).
  • Heritability varied significantly across brain regions, from 0.18 (cerebellum) to 0.76 (occipital lobe).
  • Genetic influence on deep WMH decreased with age, particularly after 75, and was higher in women.

Conclusions:

  • WMH exhibit substantial genetic influence, with regional and sex-specific variations.
  • A single additive genetic factor largely explains the shared variance between deep and periventricular WMH.
  • Findings suggest heterogeneous WMH pathogenesis influenced by genetics, sex, and age.