White matter hyperintensities and vascular risk factors in monozygotic twins

Mara ten Kate*, Carole H. Sudre, Anouk den Braber, Elles Konijnenberg, Michel G. Nivard, M. Jorge Cardoso, Philip Scheltens, Sébastien Ourselin, Dorret I. Boomsma, Frederik Barkhof, Pieter Jelle Visser

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

Cerebral white matter hyperintensities (WMHs) have been associated with vascular risk factors, both of which are under genetic influence. We examined in a monozygotic twin sample whether the association between vascular risk and WMHs is influenced by overlapping genetic factors. We included 195 cognitively normal monozygotic twins (age = 70 ± 7 years), including 94 complete pairs. Regional WMH load was estimated using an automated algorithm. Vascular risk was summarized with the Framingham score. The within–twin pair correlation for total WMHs was 0.76 and for Framingham score was 0.77. Within participants, Framingham score was associated with total and periventricular WMHs (r = 0.32). Framingham score in 1 twin was also associated with total WMHs in the co-twin (r = 0.26). Up to 83% of the relation between both traits could be explained by shared genetic effects. In conclusion, monozygotic twins have highly similar vascular risk and WMH burden, confirming a genetic background for these traits. The association between both traits is largely driven by overlapping genetic factors.

Original languageEnglish
Pages (from-to)40-48
Number of pages9
JournalNeurobiology of Aging
Volume66
Issue numberJune
Early online date10 Feb 2018
DOIs
Publication statusPublished - Jun 2018

Funding

CHS, MJC, and SO have a patent pending #P110021GB—“Representing 3D Regional Brain Biomarkers in 2D”. FB serves as a consultant for Bayer-Schering Pharma, Biogen-Idec, TEVA, Merck Serono, Novartis, Roche, Synthon BV, Jansen, and Genzyme. PJV serves as an advisory board member of Eli-Lilly, is consultant for Janssen, and has received grants from GE Healthcare and Biogen. PS has received grant support for the VU University Alzheimer Center from GE Healthcare, Nutricia Research, Piramal, and MERCK. In the past 2 years, he has received consultancy/speaker fees (paid to the institution) from Probiodrug, EIP Pharma, Sanofi, Novartis, Piramal, and GE Healthcare. This work has received support from the EU/EFPIA Innovative Medicines Initiative Joint Undertaking (EMIF grant: 115372). The VUmc Alzheimer Center is supported by Alzheimer Nederland and Stichting VUmc Fonds. Research of the VUmc Alzheimer Center is part of the neurodegeneration research program of Neuroscience Amsterdam. This work was partially funded by the UK Medical Research Council (MR/M023664/1), Wolfson Foundation, the EPSRC (EP/L016478/1, EP/M020533/1), the MRC (MR/J01107X/1), the EU Horizon 2020 (grant number: 666992), the EU-FP7 project VPH-DARE@IT (FP7-ICT-2011-9-601055), and the National Institute for Health Research University College London Hospitals Biomedical Research Centre. Appendix A

FundersFunder number
Alzheimer Nederland and Stichting VUmc Fonds
EU-FP7FP7-ICT-2011-9-601055
EU/EFPIA115372
Nutricia Research
Piramal
GE Healthcare
Medical Research CouncilMR/M023664/1, MR/J01107X/1
Engineering and Physical Sciences Research CouncilEP/M020533/1, EP/L016478/1
Wolfson Foundation
Vrije Universiteit Amsterdam
Horizon 2020666992
UCLH Biomedical Research Centre

    Keywords

    • Monozygotic twins
    • Vascular risk factors
    • White matter hyperintensities

    Cohort Studies

    • Netherlands Twin Register (NTR)

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