2021
DOI: 10.1038/s41588-021-00785-3
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Genome sequencing analysis identifies new loci associated with Lewy body dementia and provides insights into its genetic architecture

Abstract: The genetic basis of Lewy body dementia (LBD) is not well understood. Here, we performed whole-genome sequencing in large cohorts of LBD cases and neurologically healthy controls to study the genetic architecture of this understudied form of dementia and to generate a resource for the scientific community. Genome-wide association analysis identified five independent risk loci, whereas genome-wide gene-aggregation tests implicated mutations in the gene GBA . Genetic risk scores demonstrat… Show more

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Cited by 267 publications
(274 citation statements)
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“…With LD-score regression, the liability-scale narrow-sense heritability of iRBD based on common variants is calculated at 12.3% (standard error=0.07), similar to the recently reported 10.8% heritability for DLB. 8…”
Section: Resultsmentioning
confidence: 99%
“…With LD-score regression, the liability-scale narrow-sense heritability of iRBD based on common variants is calculated at 12.3% (standard error=0.07), similar to the recently reported 10.8% heritability for DLB. 8…”
Section: Resultsmentioning
confidence: 99%
“…Genetically, the differences between PDD and DLB are not well-characterised, although APOE , GBA and SNCA mutations have been implicated in both [ 2 , 112 ]. More is known about the genetic risk factors contributing to PD and DLB, which share some risk loci ( GBA , TMEM175 and SNCA ) and pathways (lysosomal and endocytic pathways) [ 21 , 29 , 50 , 77 , 93 ]. However, there is also evidence that association signals at SNCA may be distinct in PD and DLB (i.e.…”
Section: Introductionmentioning
confidence: 99%
“…However, there is also evidence that association signals at SNCA may be distinct in PD and DLB (i.e. located at the 3’ and 5’ end of the SNCA gene, respectively) [ 21 , 29 , 48 , 50 ], and while risk pathways are shared, PD genetic risk factors only explain a small portion of DLB phenotypic variance [ 29 , 49 ].…”
Section: Introductionmentioning
confidence: 99%
“…Lewy body dementia is the most common hallmark of neurodegenerative diseases. Chia et al (2021) performed whole-genome sequencing in controls and Lewy body dementia cases (Alzheimer’s and Parkinson’s diseases) to find out the genetic architecture [ 150 ]. Their study revealed that GBA1 , BIN1 , TMEM175 , SNCA-AS1 , and APOE loci are responsible for increases in Lewy body pathogenesis [ 150 ].…”
Section: Discussionmentioning
confidence: 99%