TY - JOUR
T1 - The genetic overlap between Alzheimer's disease, amyotrophic lateral sclerosis, Lewy body dementia, and Parkinson's disease
AU - Wightman, Douglas P.
AU - Savage, Jeanne E.
AU - Tissink, Elleke
AU - Romero, Cato
AU - Jansen, Iris E.
AU - Posthuma, Danielle
N1 - Funding Information: DP was funded by The Netherlands Organization for Scientific Research ( NWO 453–14-005 ), NWO Gravitation : BRAINSCAPES: A Roadmap from Neurogenetics to Neurobiology (Grant No. 024.004.012 ), and a European Research Council advanced grant (Grant No. ERC-2018-AdG GWAS2FUNC 834057 ). DW was funded by NWO Gravitation: BRAINSCAPES: A Roadmap from Neurogenetics to Neurobiology (Grant No. 024.004.012 ). IEJ was funded by NWO Gravitation: BRAINSCAPES: A Roadmap from Neurogenetics to Neurobiology (Grant No. 024.004.012 ). JES was supported by funding from the Amsterdam Neuroscience Alliance Project . CR was funded by NWO Gravitation: BRAINSCAPES: A Roadmap from Neurogenetics to Neurobiology (Grant No. 024.004.012 ). Analyses were carried out on the Genetic Cluster Computer hosted by the Dutch National computing and Networking Services SurfSARA. Funding Information: DP was funded by The Netherlands Organization for Scientific Research (NWO 453–14-005), NWO Gravitation: BRAINSCAPES: A Roadmap from Neurogenetics to Neurobiology (Grant No. 024.004.012), and a European Research Council advanced grant (Grant No. ERC-2018-AdG GWAS2FUNC 834057). DW was funded by NWO Gravitation: BRAINSCAPES: A Roadmap from Neurogenetics to Neurobiology (Grant No. 024.004.012). IEJ was funded by NWO Gravitation: BRAINSCAPES: A Roadmap from Neurogenetics to Neurobiology (Grant No. 024.004.012). JES was supported by funding from the Amsterdam Neuroscience Alliance Project. CR was funded by NWO Gravitation: BRAINSCAPES: A Roadmap from Neurogenetics to Neurobiology (Grant No. 024.004.012). Analyses were carried out on the Genetic Cluster Computer hosted by the Dutch National computing and Networking Services SurfSARA. DPW and ET analyzed the data. DPW wrote the manuscript. DPW, IEJ, JES, CR, ET, and DP designed the analysis plan. IEJ, JES, and DP supervised the project. Authors declare that data contained in the manuscript being submitted have not been previously published, have not been submitted elsewhere and will not be submitted elsewhere while under consideration at Neurobiology of Aging. All authors have reviewed the contents of the manuscript being submitted, approve of its contents and validate the accuracy of the data. Publisher Copyright: © 2023 The Authors
PY - 2023/7
Y1 - 2023/7
N2 - Neurodegenerative diseases are a group of disorders characterized by neuronal cell death causing a variety of physical and mental problems. While these disorders can be characterized by their phenotypic presentation within the nervous system, their aetiologies differ to varying degrees. The majority of previous genetic evidence for overlap between neurodegenerative diseases has been pairwise. In this study, we aimed to identify overlap between the 4 investigated neurodegenerative disorders (Alzheimer's disease, amyotrophic lateral sclerosis, Lewy body dementia, and Parkinson's disease) at the variant, gene, genomic locus, gene-set, cell, or tissue level, with specific interest in overlap between 3 or more diseases. Using local genetic correlation, we found 2 loci (TMEM175 and HLA) that were shared across 3 disorders. We also highlighted genes, genomic loci, gene sets, cell types, and tissue types which may be important to 2 or more disorders by analyzing the association of variants with a common factor estimated from the 4 disorders. Our study successfully highlighted genetic loci and tissues associated with 2 or more neurodegenerative diseases.
AB - Neurodegenerative diseases are a group of disorders characterized by neuronal cell death causing a variety of physical and mental problems. While these disorders can be characterized by their phenotypic presentation within the nervous system, their aetiologies differ to varying degrees. The majority of previous genetic evidence for overlap between neurodegenerative diseases has been pairwise. In this study, we aimed to identify overlap between the 4 investigated neurodegenerative disorders (Alzheimer's disease, amyotrophic lateral sclerosis, Lewy body dementia, and Parkinson's disease) at the variant, gene, genomic locus, gene-set, cell, or tissue level, with specific interest in overlap between 3 or more diseases. Using local genetic correlation, we found 2 loci (TMEM175 and HLA) that were shared across 3 disorders. We also highlighted genes, genomic loci, gene sets, cell types, and tissue types which may be important to 2 or more disorders by analyzing the association of variants with a common factor estimated from the 4 disorders. Our study successfully highlighted genetic loci and tissues associated with 2 or more neurodegenerative diseases.
KW - Alzheimer's disease
KW - Amyotrophic lateral sclerosis
KW - Genetic overlap
KW - Global genetic correlation
KW - Lewy body dementia
KW - Local genetic correlation
KW - Parkinson's disease
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85152119929&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/37045620
UR - http://www.scopus.com/inward/record.url?scp=85152119929&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85152119929&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.neurobiolaging.2023.03.004
DO - https://doi.org/10.1016/j.neurobiolaging.2023.03.004
M3 - Article
C2 - 37045620
SN - 0197-4580
VL - 127
SP - 99
EP - 112
JO - Neurobiology of aging
JF - Neurobiology of aging
ER -
