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Heritability and genetic variance of dementia with Lewy bodies

Guerreiro, Rita ; Londos, Elisabet LU and Bras, Jose (2019) In Neurobiology of Disease 127. p.492-501
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... (More)
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. © 2019 Elsevier Inc. (Less)
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author
author collaboration
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Dementia, Genetic correlation, Genetic variance, Lewy bodies
in
Neurobiology of Disease
volume
127
pages
10 pages
publisher
Elsevier
external identifiers
  • scopus:85064074557
ISSN
0969-9961
DOI
10.1016/j.nbd.2019.04.004
language
English
LU publication?
yes
additional info
Export Date: 24 April 2019
id
6f3d41c8-ef68-4340-ad12-8375abfb9791
date added to LUP
2019-04-24 13:11:29
date last changed
2020-02-26 07:21:55
@article{6f3d41c8-ef68-4340-ad12-8375abfb9791,
  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. © 2019 Elsevier Inc.},
  author       = {Guerreiro, Rita and Londos, Elisabet and Bras, Jose},
  issn         = {0969-9961},
  language     = {eng},
  pages        = {492--501},
  publisher    = {Elsevier},
  series       = {Neurobiology of Disease},
  title        = {Heritability and genetic variance of dementia with Lewy bodies},
  url          = {http://dx.doi.org/10.1016/j.nbd.2019.04.004},
  doi          = {10.1016/j.nbd.2019.04.004},
  volume       = {127},
  year         = {2019},
}