Heritability and Shared Environmental Effects of Brain Diseases in 12,040 Extended Families

Authors

• Janna I R Dijkstra
• Marc Hulsman
• Lisa Waterink
• Henne Holstege
• Charlotte E Teunissen
• Wouter F L Christiaansen
• Bryan A de Jong
• Peter Kochunov
• Brian Donohue
• Marissa D Zwan
• Anouk den Braber
• Lisa Vermunt
• Sven J van der Lee

Language

English

Publication Date

1-1-2025

Journal

npj Dementia

DOI

10.1038/s44400-025-00030-2

PMID

41195301

PMCID

PMC12583135

PubMedCentral® Posted Date

11-3-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Brain diseases have complex patterns of genetic and environmental risk factors, and better understanding of these risks is required for more effective prevention strategies. Participants of the Dutch Brain Research Registry provided detailed information on family structure and occurrence of brain diseases. A total of 12,040 participants (73% female, aged 64.9 ± 11 years) provided information on 101,379 family members (53% female, aged 62 ± 25 years). We estimated heritability (h2) of the nine most common brain diseases using polygenic modeling in SOLAR and assessed variations in h2 through bootstrapping; Alzheimer’s disease (AD) (h2 = 73, range 53–86, Pfdr <  0.001), ALS (h2 = 72, range 10–98, Pfdr = 0.030), frontotemporal dementia (FTD) (h2 = 48, range 0–97, Pfdr = 0.132), vascular dementia (VaD) (h2 = 41, range 7–64, P = 0.003), Lewy Body dementia (h2 = 34, range 0–58, P = 0.132), iCVA (h2 = 27, 6–59, Pfdr = 0.013), hCVA (h2 = 29, 8–57, Pfdr = 0.007), Parkinson’s disease (PD) (h2 = 38, 6–66, Pfdr = 0.013), and multiple sclerosis (h2 = 10, 10–97, Pfdr <  0.001). Shared environmental effects could be estimated for AD (c2 = 5.8%, Pfdr = 0.011), VaD (c2 = 9.0%, Pfdr = 0.021), FTD (c2 = 9.7%, Pfdr = 0.33), iCVA (c2 = 15.9%, Pfdr <  0.001), hCVA (c2 = 14.9%, Pfdr = 0.005), and PD (c2 = 7.5%, Pfdr = 0.25). These findings underscore the significance of genetic contribution to most brain diseases and the important role of shared environments in AD and vascular-related conditions, highlighting initiatives to mitigate modifiable risk factors.

Keywords

Dementia, Neurodegenerative diseases, Parkinson's disease, Stroke, Genetics

Published Open-Access

yes

Recommended Citation

Dijkstra, Janna I R; Hulsman, Marc; Waterink, Lisa; et al., "Heritability and Shared Environmental Effects of Brain Diseases in 12,040 Extended Families" (2025). Faculty, Staff and Student Publications. 4398.
https://digitalcommons.library.tmc.edu/uthmed_docs/4398