Scrutinizing neurodegenerative diseases: decoding the complex genetic architectures through a multi-omics lens
Abstract Neurodegenerative diseases present complex genetic architectures, reflecting a continuum from monogenic to oligogenic and polygenic models. Recent advances in multi-omics data, coupled with systems genetics, have significantly refined our understanding of how these data impact neurodegenera...
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BMC
2024-12-01
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| Series: | Human Genomics |
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| Online Access: | https://doi.org/10.1186/s40246-024-00704-7 |
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| author | Relu Cocoș Bogdan Ovidiu Popescu |
| author_facet | Relu Cocoș Bogdan Ovidiu Popescu |
| author_sort | Relu Cocoș |
| collection | DOAJ |
| description | Abstract Neurodegenerative diseases present complex genetic architectures, reflecting a continuum from monogenic to oligogenic and polygenic models. Recent advances in multi-omics data, coupled with systems genetics, have significantly refined our understanding of how these data impact neurodegenerative disease mechanisms. To contextualize these genetic discoveries, we provide a comprehensive critical overview of genetic architecture concepts, from Mendelian inheritance to the latest insights from oligogenic and omnigenic models. We explore the roles of common and rare genetic variants, gene-gene and gene-environment interactions, and epigenetic influences in shaping disease phenotypes. Additionally, we emphasize the importance of multi-omics layers including genomic, transcriptomic, proteomic, epigenetic, and metabolomic data in elucidating the molecular mechanisms underlying neurodegeneration. Special attention is given to missing heritability and the contribution of rare variants, particularly in the context of pleiotropy and network pleiotropy. We examine the application of single-cell omics technologies, transcriptome-wide association studies, and epigenome-wide association studies as key approaches for dissecting disease mechanisms at tissue- and cell-type levels. Our review introduces the OmicPeak Disease Trajectory Model, a conceptual framework for understanding the genetic architecture of neurodegenerative disease progression, which integrates multi-omics data across biological layers and time points. This review highlights the critical importance of adopting a systems genetics approach to unravel the complex genetic architecture of neurodegenerative diseases. Finally, this emerging holistic understanding of multi-omics data and the exploration of the intricate genetic landscape aim to provide a foundation for establishing more refined genetic architectures of these diseases, enhancing diagnostic precision, predicting disease progression, elucidating pathogenic mechanisms, and refining therapeutic strategies for neurodegenerative conditions. |
| format | Article |
| id | doaj-art-b179686928a145a5a66d048dbb997a39 |
| institution | Kabale University |
| issn | 1479-7364 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Human Genomics |
| spelling | doaj-art-b179686928a145a5a66d048dbb997a392025-01-05T12:41:17ZengBMCHuman Genomics1479-73642024-12-0118112510.1186/s40246-024-00704-7Scrutinizing neurodegenerative diseases: decoding the complex genetic architectures through a multi-omics lensRelu Cocoș0Bogdan Ovidiu Popescu1Department of Medical Genetics, ‘Carol Davila’ University of Medicine and PharmacyDepartment of Clinical Neurosciences, ‘Carol Davila’ University of Medicine and PharmacyAbstract Neurodegenerative diseases present complex genetic architectures, reflecting a continuum from monogenic to oligogenic and polygenic models. Recent advances in multi-omics data, coupled with systems genetics, have significantly refined our understanding of how these data impact neurodegenerative disease mechanisms. To contextualize these genetic discoveries, we provide a comprehensive critical overview of genetic architecture concepts, from Mendelian inheritance to the latest insights from oligogenic and omnigenic models. We explore the roles of common and rare genetic variants, gene-gene and gene-environment interactions, and epigenetic influences in shaping disease phenotypes. Additionally, we emphasize the importance of multi-omics layers including genomic, transcriptomic, proteomic, epigenetic, and metabolomic data in elucidating the molecular mechanisms underlying neurodegeneration. Special attention is given to missing heritability and the contribution of rare variants, particularly in the context of pleiotropy and network pleiotropy. We examine the application of single-cell omics technologies, transcriptome-wide association studies, and epigenome-wide association studies as key approaches for dissecting disease mechanisms at tissue- and cell-type levels. Our review introduces the OmicPeak Disease Trajectory Model, a conceptual framework for understanding the genetic architecture of neurodegenerative disease progression, which integrates multi-omics data across biological layers and time points. This review highlights the critical importance of adopting a systems genetics approach to unravel the complex genetic architecture of neurodegenerative diseases. Finally, this emerging holistic understanding of multi-omics data and the exploration of the intricate genetic landscape aim to provide a foundation for establishing more refined genetic architectures of these diseases, enhancing diagnostic precision, predicting disease progression, elucidating pathogenic mechanisms, and refining therapeutic strategies for neurodegenerative conditions.https://doi.org/10.1186/s40246-024-00704-7NeurodegenerativeGenetic architectureHeritabilityMulti-omicsNetworks |
| spellingShingle | Relu Cocoș Bogdan Ovidiu Popescu Scrutinizing neurodegenerative diseases: decoding the complex genetic architectures through a multi-omics lens Human Genomics Neurodegenerative Genetic architecture Heritability Multi-omics Networks |
| title | Scrutinizing neurodegenerative diseases: decoding the complex genetic architectures through a multi-omics lens |
| title_full | Scrutinizing neurodegenerative diseases: decoding the complex genetic architectures through a multi-omics lens |
| title_fullStr | Scrutinizing neurodegenerative diseases: decoding the complex genetic architectures through a multi-omics lens |
| title_full_unstemmed | Scrutinizing neurodegenerative diseases: decoding the complex genetic architectures through a multi-omics lens |
| title_short | Scrutinizing neurodegenerative diseases: decoding the complex genetic architectures through a multi-omics lens |
| title_sort | scrutinizing neurodegenerative diseases decoding the complex genetic architectures through a multi omics lens |
| topic | Neurodegenerative Genetic architecture Heritability Multi-omics Networks |
| url | https://doi.org/10.1186/s40246-024-00704-7 |
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