White matter hyperintensities are under strong genetic influence

Perminder S. Sachdev*, Anbupalam Thalamuthu, Karen A. Mather, David Ames, Margaret J. Wright, Wei Wen, OATS Collaborative Research Team

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    22 Citations (Scopus)

    Abstract

    Background and Purpose - The genetic basis of white matter hyperintensities (WMH) is still unknown. This study examines the heritability of WMH in both sexes and in different brain regions, and the influence of age. Methods - Participants from the Older Australian Twins Study were recruited (n=320; 92 monozygotic and 68 dizygotic pairs) who volunteered for magnetic resonance imaging scans and medical assessments. Heritability, that is, the ratio of the additive genetic variance to the total phenotypic variance, was estimated using the twin design. Results - Heritability was high for total WMH volume (0.76), and for periventricular WMH (0.64) and deep WMH (0.77), and varied from 0.18 for the cerebellum to 0.76 for the occipital lobe. The genetic correlation between deep and periventricular WMH regions was 0.85, with one additive genetics factor accounting for most of the shared variance. Heritability was consistently higher in women in the cerebral regions. Heritability in deep but not periventricular WMH declined with age, in particular after the age of 75. Conclusions - WMH have a strong genetic influence but this is not uniform through the brain, being higher for deep than periventricular WMH and in the cerebral regions. The genetic influence is higher in women, and there is an age-related decline, most markedly for deep WMH. The data suggest some heterogeneity in the pathogenesis of WMH for different brain regions and for men and women.

    Original languageEnglish
    Pages (from-to)1422-1428
    Number of pages7
    JournalStroke
    Volume47
    Issue number6
    DOIs
    Publication statusPublished - 1 Jun 2016

    Keywords

    • aging
    • epidemiology
    • heritable quantitative trait
    • magnetic resonance imaging
    • white matter

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