Genetic and environmental effects on the development of white matter hyperintensities in a middle age twin population

Alijanpourotaghsara, Amirreza and Strelnikov, David and Piroska, Marton and Szalontai, Laszlo and Forgó, Bianka and Jokkel, Zsofia and Persely, Alíz and Hernyes, Anita and Kozák, Lajos R. and Szabó, Ádám György and Maurovich-Horvat, Pál and Tárnoki, Ádám Domonkos and Tárnoki, Dávid László (2022) Genetic and environmental effects on the development of white matter hyperintensities in a middle age twin population. MEDICINA. ISSN 1010-660X (Submitted)

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Abstract

Introduction: White matter hyperintensities (WMH) are indicative of white matter brain lesions in the magnetic resonance imaging (MRI), which can be used as a marker for brain aging, cerebrovascular and neurodegenerative disorders. Twin studies revealed substantial but not uniform WMH heritability in elderly twins. The objective of our study was to investigate the genetic and environmental components of WMH, as well as their importance in a healthy twin population, utilizing 3T MRI scanners in a middle-aged twin population. Methods: Brain MRI was performed on 120 healthy adult twins from the Hungarian Twin Registry on a 3T scanner (86 monozygotic, MZ, and 34 dizygotic, DZ twins; median age 50±26.5 years, 72.5% female). The count of WMH on FLAIR images was calculated using both an automated volumetry pipeline (volBrain) and human processing. The age- and sexadjusted MZ and DZ intra-pair correlations were determined, and the total variance was decomposed into genetic, shared, and unique environmental components using structural equation modeling. Results: Age and sex adjusted MZ intrapair correlations were higher than DZ correlations indicating moderate genetic influence in each lesions (rMZ=0.466, rDZ=-0.025 for total count; rMZ=0.482, rDZ=0.093 for deep white matter count; rMZ=0.739, rDZ=0.39 for infratentorial count; rMZ=0.573, rDZ=0.372 for cerebellar count and rMZ=0.473, rDZ=0.19 for periventricular count), indicating a moderate heritability (A=40.3%, A=45%, A=72.7% and A=55.5%and 47.2% respectively). The rest of the variance was influenced by unique environmental effects (E between 27.3% and 59.7%, respectively). Conclusions: The number of WMH lesions is moderately influenced by genetic effects, particularly in the infratentorial region in middle-aged twins. These results suggest that the distribution of WMH in various brain regions is heterogeneous.

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