دورية أكاديمية
Systematic investigation of allelic regulatory activity of schizophrenia-associated common variants
| العنوان: | Systematic investigation of allelic regulatory activity of schizophrenia-associated common variants |
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| المؤلفون: | Jessica C. McAfee, Sool Lee, Jiseok Lee, Jessica L. Bell, Oleh Krupa, Jessica Davis, Kimberly Insigne, Marielle L. Bond, Nanxiang Zhao, Alan P. Boyle, Douglas H. Phanstiel, Michael I. Love, Jason L. Stein, W. Brad Ruzicka, Jose Davila-Velderrain, Sriram Kosuri, Hyejung Won |
| المصدر: | Cell Genomics, Vol 3, Iss 10, Pp 100404- (2023) |
| بيانات النشر: | Elsevier, 2023. |
| سنة النشر: | 2023 |
| المجموعة: | LCC:Genetics LCC:Internal medicine |
| مصطلحات موضوعية: | MPRA, schizophrenia, GWAS, non-coding variants, accessibility-by-contact model, variant function, Genetics, QH426-470, Internal medicine, RC31-1245 |
| الوصف: | Summary: Genome-wide association studies (GWASs) have successfully identified 145 genomic regions that contribute to schizophrenia risk, but linkage disequilibrium makes it challenging to discern causal variants. We performed a massively parallel reporter assay (MPRA) on 5,173 fine-mapped schizophrenia GWAS variants in primary human neural progenitors and identified 439 variants with allelic regulatory effects (MPRA-positive variants). Transcription factor binding had modest predictive power, while fine-map posterior probability, enhancer overlap, and evolutionary conservation failed to predict MPRA-positive variants. Furthermore, 64% of MPRA-positive variants did not exhibit expressive quantitative trait loci signature, suggesting that MPRA could identify yet unexplored variants with regulatory potentials. To predict the combinatorial effect of MPRA-positive variants on gene regulation, we propose an accessibility-by-contact model that combines MPRA-measured allelic activity with neuronal chromatin architecture. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2666-979X |
| العلاقة: | http://www.sciencedirect.com/science/article/pii/S2666979X23002185Test; https://doaj.org/toc/2666-979XTest |
| DOI: | 10.1016/j.xgen.2023.100404 |
| الوصول الحر: | https://doaj.org/article/8699b54b8aa149bd9c2642416266fe09Test |
| رقم الانضمام: | edsdoj.8699b54b8aa149bd9c2642416266fe09 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 2666979X |
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| DOI: | 10.1016/j.xgen.2023.100404 |