Heritability and genetic variance of dementia with Lewy bodies

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http://hdl.handle.net/10138/313958

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Int Parkinson's Dis Genomics Cons , Guerreiro , R , Escott-Price , V , Tienari , P J , Myllykangas , L & Oinas , M 2019 , ' Heritability and genetic variance of dementia with Lewy bodies ' , Neurobiology of Disease , vol. 127 , pp. 492-501 . https://doi.org/10.1016/j.nbd.2019.04.004

Title: Heritability and genetic variance of dementia with Lewy bodies
Author: Int Parkinson's Dis Genomics Cons; Guerreiro, Rita; Escott-Price, Valentina; Tienari, Pentti J.; Myllykangas, Liisa; Oinas, Minna
Contributor: University of Helsinki, HUS Neurocenter
University of Helsinki, Department of Pathology
University of Helsinki, HUS Neurocenter
Date: 2019-07
Language: eng
Number of pages: 10
Belongs to series: Neurobiology of Disease
ISSN: 0969-9961
URI: http://hdl.handle.net/10138/313958
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.
Subject: Genetic variance
Dementia
Lewy bodies
Genetic correlation
GENOME-WIDE ASSOCIATION
MISSING HERITABILITY
ALZHEIMERS-DISEASE
POLYGENIC RISK
LOCI
ARCHITECTURE
METAANALYSIS
3112 Neurosciences
3124 Neurology and psychiatry
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