Retrotransposon insertions associated with risk of neurologic and psychiatric diseases
Published 2022. This article is a U.S. Government work and is in the public domain in the USA..
Transposable elements (TEs) are active in neuronal cells raising the question whether TE insertions contribute to risk of neuropsychiatric disease. While genome-wide association studies (GWAS) serve as a tool to discover genetic loci associated with neuropsychiatric diseases, unfortunately GWAS do not directly detect structural variants such as TEs. To examine the role of TEs in psychiatric and neurologic disease, we evaluated 17,000 polymorphic TEs and find 76 are in linkage disequilibrium with disease haplotypes (P < 10-6 ) defined by GWAS. From these 76 polymorphic TEs, we identify potentially causal candidates based on having insertions in genomic regions of regulatory chromatin and on having associations with altered gene expression in brain tissues. We show that lead candidate insertions have regulatory effects on gene expression in human neural stem cells altering the activity of a minimal promoter. Taken together, we identify 10 polymorphic TE insertions that are potential candidates on par with other variants for having a causal role in neurologic and psychiatric disorders.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:24 |
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| Enthalten in: |
EMBO reports - 24(2023), 1 vom: 09. Jan., Seite e55197 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ahn, Hyo Won [VerfasserIn] |
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| Links: |
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| Themen: |
Alu |
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| Anmerkungen: |
Date Completed 10.01.2023 Date Revised 12.11.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.15252/embr.202255197 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM34880802X |
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| 245 | 1 | 0 | |a Retrotransposon insertions associated with risk of neurologic and psychiatric diseases |
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| 500 | |a Date Revised 12.11.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Published 2022. This article is a U.S. Government work and is in the public domain in the USA. | ||
| 520 | |a Transposable elements (TEs) are active in neuronal cells raising the question whether TE insertions contribute to risk of neuropsychiatric disease. While genome-wide association studies (GWAS) serve as a tool to discover genetic loci associated with neuropsychiatric diseases, unfortunately GWAS do not directly detect structural variants such as TEs. To examine the role of TEs in psychiatric and neurologic disease, we evaluated 17,000 polymorphic TEs and find 76 are in linkage disequilibrium with disease haplotypes (P < 10-6 ) defined by GWAS. From these 76 polymorphic TEs, we identify potentially causal candidates based on having insertions in genomic regions of regulatory chromatin and on having associations with altered gene expression in brain tissues. We show that lead candidate insertions have regulatory effects on gene expression in human neural stem cells altering the activity of a minimal promoter. Taken together, we identify 10 polymorphic TE insertions that are potential candidates on par with other variants for having a causal role in neurologic and psychiatric disorders | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a Research Support, N.I.H., Intramural | |
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| 650 | 4 | |a psychiatric disease | |
| 650 | 4 | |a transposable elements | |
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| 650 | 7 | |a DNA Transposable Elements |2 NLM | |
| 700 | 1 | |a Worman, Zelia F |e verfasserin |4 aut | |
| 700 | 1 | |a Lechsinska, Arianna |e verfasserin |4 aut | |
| 700 | 1 | |a Payer, Lindsay M |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Tongguang |e verfasserin |4 aut | |
| 700 | 1 | |a Malik, Nasir |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Wenxue |e verfasserin |4 aut | |
| 700 | 1 | |a Burns, Kathleen H |e verfasserin |4 aut | |
| 700 | 1 | |a Nath, Avindra |e verfasserin |4 aut | |
| 700 | 1 | |a Levin, Henry L |e verfasserin |4 aut | |
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