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Article Dans Une Revue Neurobiology of Disease Année : 2019

Heritability and genetic variance of dementia with Lewy bodies

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

Résumé

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 et versions

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

Identifiants

Citer

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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