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Journal Articles Neurobiology of Disease Year : 2019

Heritability and genetic variance of dementia with Lewy bodies

Valentina Escott-Price
Elisabet Londos
  • Function : Author
Geidy Serrano
  • Function : Author
Thomas Beach
  • Function : Author
Douglas Galasko
  • Function : Author
Eliezer Masliah
  • Function : Author
Isabel Santana
  • Function : Author
Pau Pastor
Monica Diez-Fairen
  • Function : Author
Miquel Aguilar
  • Function : Author
Pentti Tienari
  • Function : Author
Liisa Myllykangas
  • Function : Author
Minna Oinas
  • Function : Author
Tamas Revesz
  • Function : Author
Andrew Lees
  • Function : Author
Brad Boeve
  • Function : Author
Ronald Petersen
  • Function : Author
Tanis Ferman
  • Function : Author
Neill Graff-Radford
  • Function : Author
Nigel Cairns
  • Function : Author
John Morris
  • Function : Author
Stuart Pickering-Brown
  • Function : Author
David Mann
  • Function : Author
Glenda Halliday
  • Function : Author
John Hardy
  • Function : Author
Dennis Dickson
  • Function : Author
Andrew Singleton
  • Function : Author
David Stone
  • Function : Author
Jose Bras
Peter St. George-Hyslop
  • Function : Author

Abstract

Recent large-scale genetic studies have allowed for the first glimpse of the effects of common genetic variability in dementia with Lewy bodies (DLB), identifying risk variants with appreciable effect sizes. However, it is currently well established that a substantial portion of the genetic heritable component of complex traits is not captured by genome-wide significant SNPs. To overcome this issue, we have estimated the proportion of phenotypic variance explained by genetic variability (SNP heritability) in DLB using a method that is unbiased by allele frequency or linkage disequilibrium properties of the underlying variants. This shows that the heritability of DLB is nearly twice as high as previous estimates based on common variants only (31% vs 59.9%). We also determine the amount of phenotypic variance in DLB that can be explained by recent polygenic risk scores from either Parkinson's disease (PD) or Alzheimer's disease (AD), and show that, despite being highly significant, they explain a low amount of variance. Additionally, to identify pleiotropic events that might improve our understanding of the disease, we performed genetic correlation analyses of DLB with over 200 diseases and biomedically relevant traits. Our data shows that DLB has a positive correlation with education phenotypes, which is opposite to what occurs in AD. Overall, our data suggests that novel genetic risk factors for DLB should be identified by larger GWAS and these are likely to be independent from known AD and PD risk variants.

Dates and versions

hal-04560893 , version 1 (26-04-2024)

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Rita Guerreiro, Valentina Escott-Price, Dena Hernandez, Celia Kun-Rodrigues, Owen Ross, et al.. Heritability and genetic variance of dementia with Lewy bodies. Neurobiology of Disease, 2019, 127, pp.492-501. ⟨10.1016/j.nbd.2019.04.004⟩. ⟨hal-04560893⟩
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