Analysis of rare Parkinson’s disease variants in millions of people
Abstract Although many rare variants have been reportedly associated with Parkinson’s disease (PD), many have not been replicated or have failed to replicate. Here, we conduct a large-scale replication of rare PD variants. We assessed a total of 27,590 PD cases, 6701 PD proxies, and 3,106,080 contro...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2024-01-01
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| Series: | npj Parkinson's Disease |
| Online Access: | https://doi.org/10.1038/s41531-023-00608-8 |
| _version_ | 1827382311702757376 |
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| author | Vanessa Pitz Mary B. Makarious Sara Bandres-Ciga Hirotaka Iwaki 23andMe Research Team Andrew B. Singleton Mike Nalls Karl Heilbron Cornelis Blauwendraat |
| author_facet | Vanessa Pitz Mary B. Makarious Sara Bandres-Ciga Hirotaka Iwaki 23andMe Research Team Andrew B. Singleton Mike Nalls Karl Heilbron Cornelis Blauwendraat |
| author_sort | Vanessa Pitz |
| collection | DOAJ |
| description | Abstract Although many rare variants have been reportedly associated with Parkinson’s disease (PD), many have not been replicated or have failed to replicate. Here, we conduct a large-scale replication of rare PD variants. We assessed a total of 27,590 PD cases, 6701 PD proxies, and 3,106,080 controls from three data sets: 23andMe, Inc., UK Biobank, and AMP-PD. Based on well-known PD genes, 834 variants of interest were selected from the ClinVar annotated 23andMe dataset. We performed a meta-analysis using summary statistics of all three studies. The meta-analysis resulted in five significant variants after Bonferroni correction, including variants in GBA1 and LRRK2. Another eight variants are strong candidate variants for their association with PD. Here, we provide the largest rare variant meta-analysis to date, providing information on confirmed and newly identified variants for their association with PD using several large databases. Additionally we also show the complexities of studying rare variants in large-scale cohorts. |
| first_indexed | 2024-03-08T14:17:45Z |
| format | Article |
| id | doaj.art-00d7126da364460db8cd2857981d1321 |
| institution | Directory Open Access Journal |
| issn | 2373-8057 |
| language | English |
| last_indexed | 2024-03-08T14:17:45Z |
| publishDate | 2024-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Parkinson's Disease |
| spelling | doaj.art-00d7126da364460db8cd2857981d13212024-01-14T12:16:19ZengNature Portfolionpj Parkinson's Disease2373-80572024-01-0110111010.1038/s41531-023-00608-8Analysis of rare Parkinson’s disease variants in millions of peopleVanessa Pitz0Mary B. Makarious1Sara Bandres-Ciga2Hirotaka Iwaki323andMe Research TeamAndrew B. Singleton4Mike Nalls5Karl Heilbron6Cornelis Blauwendraat7Integrative Neurogenomics Unit, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of HealthMolecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of HealthCenter for Alzheimer’s and Related Dementias (CARD), National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of HealthMolecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of HealthMolecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of HealthMolecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health23andMe, Inc.Integrative Neurogenomics Unit, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of HealthAbstract Although many rare variants have been reportedly associated with Parkinson’s disease (PD), many have not been replicated or have failed to replicate. Here, we conduct a large-scale replication of rare PD variants. We assessed a total of 27,590 PD cases, 6701 PD proxies, and 3,106,080 controls from three data sets: 23andMe, Inc., UK Biobank, and AMP-PD. Based on well-known PD genes, 834 variants of interest were selected from the ClinVar annotated 23andMe dataset. We performed a meta-analysis using summary statistics of all three studies. The meta-analysis resulted in five significant variants after Bonferroni correction, including variants in GBA1 and LRRK2. Another eight variants are strong candidate variants for their association with PD. Here, we provide the largest rare variant meta-analysis to date, providing information on confirmed and newly identified variants for their association with PD using several large databases. Additionally we also show the complexities of studying rare variants in large-scale cohorts.https://doi.org/10.1038/s41531-023-00608-8 |
| spellingShingle | Vanessa Pitz Mary B. Makarious Sara Bandres-Ciga Hirotaka Iwaki 23andMe Research Team Andrew B. Singleton Mike Nalls Karl Heilbron Cornelis Blauwendraat Analysis of rare Parkinson’s disease variants in millions of people npj Parkinson's Disease |
| title | Analysis of rare Parkinson’s disease variants in millions of people |
| title_full | Analysis of rare Parkinson’s disease variants in millions of people |
| title_fullStr | Analysis of rare Parkinson’s disease variants in millions of people |
| title_full_unstemmed | Analysis of rare Parkinson’s disease variants in millions of people |
| title_short | Analysis of rare Parkinson’s disease variants in millions of people |
| title_sort | analysis of rare parkinson s disease variants in millions of people |
| url | https://doi.org/10.1038/s41531-023-00608-8 |
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