Chromosomal inversion polymorphisms shape human brain morphology
Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved..
The impact of chromosomal inversions on human brain morphology remains underexplored. We studied 35 common inversions classified from genotypes of 33,018 adults with European ancestry. The inversions at 2p22.3, 16p11.2, and 17q21.31 reach genome-wide significance, followed by 8p23.1 and 6p21.33, in their association with cortical and subcortical morphology. The 17q21.31, 8p23.1, and 16p11.2 regions comprise the LRRC37, OR7E, and NPIP duplicated gene families. We find the 17q21.31 MAPT inversion region, known for harboring neurological risk, to be the most salient locus among common variants for shaping and patterning the cortex. Overall, we observe the inverted orientations decreasing brain size, with the exception that the 2p22.3 inversion is associated with increased subcortical volume and the 8p23.1 inversion is associated with increased motor cortex. These significant inversions are in the genomic hotspots of neuropsychiatric loci. Our findings are generalizable to 3,472 children and demonstrate inversions as essential genetic variation to understand human brain phenotypes.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:42 |
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| Enthalten in: |
Cell reports - 42(2023), 8 vom: 29. Aug., Seite 112896 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wang, Hao [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 04.09.2023 Date Revised 01.02.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.celrep.2023.112896 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM360058795 |
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| 245 | 1 | 0 | |a Chromosomal inversion polymorphisms shape human brain morphology |
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| 520 | |a Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a The impact of chromosomal inversions on human brain morphology remains underexplored. We studied 35 common inversions classified from genotypes of 33,018 adults with European ancestry. The inversions at 2p22.3, 16p11.2, and 17q21.31 reach genome-wide significance, followed by 8p23.1 and 6p21.33, in their association with cortical and subcortical morphology. The 17q21.31, 8p23.1, and 16p11.2 regions comprise the LRRC37, OR7E, and NPIP duplicated gene families. We find the 17q21.31 MAPT inversion region, known for harboring neurological risk, to be the most salient locus among common variants for shaping and patterning the cortex. Overall, we observe the inverted orientations decreasing brain size, with the exception that the 2p22.3 inversion is associated with increased subcortical volume and the 8p23.1 inversion is associated with increased motor cortex. These significant inversions are in the genomic hotspots of neuropsychiatric loci. Our findings are generalizable to 3,472 children and demonstrate inversions as essential genetic variation to understand human brain phenotypes | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a CP: Genomics | |
| 650 | 4 | |a CP: Neuroscience | |
| 650 | 4 | |a brain morphology | |
| 650 | 4 | |a gene regulation | |
| 650 | 4 | |a inversion polymorphism | |
| 650 | 4 | |a magnetic resonance imaging | |
| 650 | 4 | |a molecular QTL | |
| 650 | 4 | |a neurodevelopment | |
| 650 | 4 | |a segmental duplication | |
| 650 | 4 | |a structural variant | |
| 700 | 1 | |a Makowski, Carolina |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Yanxiao |e verfasserin |4 aut | |
| 700 | 1 | |a Qi, Anna |e verfasserin |4 aut | |
| 700 | 1 | |a Kaufmann, Tobias |e verfasserin |4 aut | |
| 700 | 1 | |a Smeland, Olav B |e verfasserin |4 aut | |
| 700 | 1 | |a Fiecas, Mark |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Jian |e verfasserin |4 aut | |
| 700 | 1 | |a Visscher, Peter M |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Chi-Hua |e verfasserin |4 aut | |
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