Title | Genome sequencing analysis identifies new loci associated with Lewy body dementia and provides insights into its genetic architecture. |
Publication Type | Journal Article |
Year of Publication | 2021 |
Authors | Chia R, Sabir MS, Bandres-Ciga S, Saez-Atienzar S, Reynolds RH, Gustavsson E, Walton RL, Ahmed S, Viollet C, Ding J et al. |
Corporate Authors | American Genome Center |
Journal | Nat Genet |
Volume | 53 |
Issue | 3 |
Pagination | 294-303 |
Date Published | 2021 03 |
ISSN | 1546-1718 |
Keywords | Adaptor Proteins, Signal Transducing, alpha-Synuclein, Alzheimer Disease, Case-Control Studies, Gene Expression Profiling, Genetic Predisposition to Disease, Genome, Human, Genome-Wide Association Study, Glucosylceramidase, Humans, Lewy Body Disease, Nuclear Proteins, Parkinson Disease, Polymorphism, Single Nucleotide, Tumor Suppressor Proteins |
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 demonstrate that LBD shares risk profiles and pathways with Alzheimer's disease and Parkinson's disease, providing a deeper molecular understanding of the complex genetic architecture of this age-related neurodegenerative condition. |
DOI | 10.1038/s41588-021-00785-3 |
Pubmed Link | https://www.ncbi.nlm.nih.gov/pubmed/33589841?dopt=Abstract |
page_expo | Internal |
Alternate Journal | Nat Genet |
PubMed ID | 33589841 |
PubMed Central ID | PMC7946812 |
Grant List | P30 AG013854 / AG / NIA NIH HHS / United States K08 AG065463 / AG / NIA NIH HHS / United States P30 AG066507 / AG / NIA NIH HHS / United States G1100540 / MRC_ / Medical Research Council / United Kingdom R01 AG017917 / AG / NIA NIH HHS / United States G0900652 / MRC_ / Medical Research Council / United Kingdom G0502157 / MRC_ / Medical Research Council / United Kingdom ZIA NS003033 / ImNIH / Intramural NIH HHS / United States U01 NS095736 / NS / NINDS NIH HHS / United States R01 NS115144 / NS / NINDS NIH HHS / United States G0400074 / MRC_ / Medical Research Council / United Kingdom ZIA AG000935 / ImNIH / Intramural NIH HHS / United States U19 AG062418 / AG / NIA NIH HHS / United States MR/L016397/1 / MRC_ / Medical Research Council / United Kingdom ZIA NS003154 / ImNIH / Intramural NIH HHS / United States MR/N008324/1 / MRC_ / Medical Research Council / United Kingdom U01 NS100620 / NS / NINDS NIH HHS / United States |
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