TOPMed imputed genomics enhances genomic atlas of the human proteome in brain, cerebrospinal fluid, and plasma
Abstract Comprehensive expression quantitative trait loci studies have been instrumental for understanding tissue-specific gene regulation and pinpointing functional genes for disease-associated loci in a tissue-specific manner. Compared to gene expressions, proteins more directly affect various bio...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-04-01
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| Series: | Scientific Data |
| Online Access: | https://doi.org/10.1038/s41597-024-03140-3 |
| _version_ | 1797199681117224960 |
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| author | Heng Yi Qijun Yang Charlie Repaci Cheolmin Matthew Lee Gyujin Heo Jigyasha Timsina Priyanka Gorijala Chengran Yang John Budde Lihua Wang Carlos Cruchaga Yun Ju Sung |
| author_facet | Heng Yi Qijun Yang Charlie Repaci Cheolmin Matthew Lee Gyujin Heo Jigyasha Timsina Priyanka Gorijala Chengran Yang John Budde Lihua Wang Carlos Cruchaga Yun Ju Sung |
| author_sort | Heng Yi |
| collection | DOAJ |
| description | Abstract Comprehensive expression quantitative trait loci studies have been instrumental for understanding tissue-specific gene regulation and pinpointing functional genes for disease-associated loci in a tissue-specific manner. Compared to gene expressions, proteins more directly affect various biological processes, often dysregulated in disease, and are important drug targets. We previously performed and identified tissue-specific protein quantitative trait loci in brain, cerebrospinal fluid, and plasma. We now enhance this work by analyzing more proteins (1,300 versus 1,079) and an almost twofold increase in high quality imputed genetic variants (8.4 million versus 4.4 million) by using TOPMed reference panel. We identified 38 genomic regions associated with 43 proteins in brain, 150 regions associated with 247 proteins in cerebrospinal fluid, and 95 regions associated with 145 proteins in plasma. Compared to our previous study, this study newly identified 12 loci in brain, 30 loci in cerebrospinal fluid, and 22 loci in plasma. Our improved genomic atlas uncovers the genetic control of protein regulation across multiple tissues. These resources are accessible through the Online Neurodegenerative Trait Integrative Multi-Omics Explorer for use by the scientific community. |
| first_indexed | 2024-04-24T07:19:37Z |
| format | Article |
| id | doaj.art-7c3c2513cce84280994e3363682db843 |
| institution | Directory Open Access Journal |
| issn | 2052-4463 |
| language | English |
| last_indexed | 2024-04-24T07:19:37Z |
| publishDate | 2024-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Data |
| spelling | doaj.art-7c3c2513cce84280994e3363682db8432024-04-21T11:08:10ZengNature PortfolioScientific Data2052-44632024-04-0111111110.1038/s41597-024-03140-3TOPMed imputed genomics enhances genomic atlas of the human proteome in brain, cerebrospinal fluid, and plasmaHeng Yi0Qijun Yang1Charlie Repaci2Cheolmin Matthew Lee3Gyujin Heo4Jigyasha Timsina5Priyanka Gorijala6Chengran Yang7John Budde8Lihua Wang9Carlos Cruchaga10Yun Ju Sung11Department of Psychiatry, Washington University School of MedicineNeuroGenomics and Informatics Center, Washington University School of MedicineNeuroGenomics and Informatics Center, Washington University School of MedicineNeuroGenomics and Informatics Center, Washington University School of MedicineDepartment of Psychiatry, Washington University School of MedicineDepartment of Psychiatry, Washington University School of MedicineDepartment of Psychiatry, Washington University School of MedicineDepartment of Psychiatry, Washington University School of MedicineDepartment of Psychiatry, Washington University School of MedicineDepartment of Psychiatry, Washington University School of MedicineDepartment of Psychiatry, Washington University School of MedicineDepartment of Psychiatry, Washington University School of MedicineAbstract Comprehensive expression quantitative trait loci studies have been instrumental for understanding tissue-specific gene regulation and pinpointing functional genes for disease-associated loci in a tissue-specific manner. Compared to gene expressions, proteins more directly affect various biological processes, often dysregulated in disease, and are important drug targets. We previously performed and identified tissue-specific protein quantitative trait loci in brain, cerebrospinal fluid, and plasma. We now enhance this work by analyzing more proteins (1,300 versus 1,079) and an almost twofold increase in high quality imputed genetic variants (8.4 million versus 4.4 million) by using TOPMed reference panel. We identified 38 genomic regions associated with 43 proteins in brain, 150 regions associated with 247 proteins in cerebrospinal fluid, and 95 regions associated with 145 proteins in plasma. Compared to our previous study, this study newly identified 12 loci in brain, 30 loci in cerebrospinal fluid, and 22 loci in plasma. Our improved genomic atlas uncovers the genetic control of protein regulation across multiple tissues. These resources are accessible through the Online Neurodegenerative Trait Integrative Multi-Omics Explorer for use by the scientific community.https://doi.org/10.1038/s41597-024-03140-3 |
| spellingShingle | Heng Yi Qijun Yang Charlie Repaci Cheolmin Matthew Lee Gyujin Heo Jigyasha Timsina Priyanka Gorijala Chengran Yang John Budde Lihua Wang Carlos Cruchaga Yun Ju Sung TOPMed imputed genomics enhances genomic atlas of the human proteome in brain, cerebrospinal fluid, and plasma Scientific Data |
| title | TOPMed imputed genomics enhances genomic atlas of the human proteome in brain, cerebrospinal fluid, and plasma |
| title_full | TOPMed imputed genomics enhances genomic atlas of the human proteome in brain, cerebrospinal fluid, and plasma |
| title_fullStr | TOPMed imputed genomics enhances genomic atlas of the human proteome in brain, cerebrospinal fluid, and plasma |
| title_full_unstemmed | TOPMed imputed genomics enhances genomic atlas of the human proteome in brain, cerebrospinal fluid, and plasma |
| title_short | TOPMed imputed genomics enhances genomic atlas of the human proteome in brain, cerebrospinal fluid, and plasma |
| title_sort | topmed imputed genomics enhances genomic atlas of the human proteome in brain cerebrospinal fluid and plasma |
| url | https://doi.org/10.1038/s41597-024-03140-3 |
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