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| PMID |
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| TITLE |
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| The Evolutionary History of Common Genetic Variants Influencing Human Cortical Surface Area. |
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| ABSTRACT |
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| Structural brain changes along the lineage leading to modern Homo sapiens contributed to our distinctive cognitive and social abilities. However, the evolutionarily relevant molecular variants impacting key aspects of neuroanatomy are largely unknown. Here, we integrate evolutionary annotations of the genome at diverse timescales with common variant associations from large-scale neuroimaging genetic screens. We find that alleles with evidence of recent positive polygenic selection over the past 2000-3000 years are associated with increased surface area (SA) of the entire cortex, as well as specific regions, including those involved in spoken language and visual processing. Therefore, polygenic selective pressures impact the structure of specific cortical areas even over relatively recent timescales. Moreover, common sequence variation within human gained enhancers active in the prenatal cortex is associated with postnatal global SA. We show that such variation modulates the function of a regulatory element of the developmentally relevant transcription factor HEY2 in human neural progenitor cells and is associated with structural changes in the inferior frontal cortex. These results indicate that non-coding genomic regions active during prenatal cortical development are involved in the evolution of human brain structure and identify novel regulatory elements and genes impacting modern human brain structure. |
| © The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com. |
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| DATE PUBLISHED |
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| HISTORY |
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| PUBSTATUS |
PUBSTATUSDATE |
| received |
2020/03/18 |
| revised |
2020/10/09 |
| accepted |
2020/10/09 |
| pubmed |
2020/12/09 06:00 |
| medline |
2020/12/09 06:00 |
| entrez |
2020/12/08 17:18 |
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| AUTHORS |
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| NAME |
COLLECTIVENAME |
LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
AFFILIATIONINFO |
| Tilot AK |
|
Tilot |
Amanda K |
AK |
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Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA 90292, USA. |
| Khramtsova EA |
|
Khramtsova |
Ekaterina A |
EA |
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Computational Sciences, Janssen Pharmaceuticals, Spring House, PA 19477, USA. |
| Liang D |
|
Liang |
Dan |
D |
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UNC Neuroscience Center, University of North Carolina, Chapel Hill, NC 27599, USA. |
| Grasby KL |
|
Grasby |
Katrina L |
KL |
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Psychiatric Genetics, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia. |
| Jahanshad N |
|
Jahanshad |
Neda |
N |
|
Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA 90292, USA. |
| Painter J |
|
Painter |
Jodie |
J |
|
Psychiatric Genetics, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia. |
| Colodro-Conde L |
|
Colodro-Conde |
Lucía |
L |
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Psychiatric Genetics, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia. |
| Bralten J |
|
Bralten |
Janita |
J |
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Radboud University Medical Center, 6525 XZ Nijmegen, Netherlands. |
| Hibar DP |
|
Hibar |
Derrek P |
DP |
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Genentech, Inc., South San Francisco, CA 94080, USA. |
| Lind PA |
|
Lind |
Penelope A |
PA |
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Psychiatric Genetics, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia. |
| Liu S |
|
Liu |
Siyao |
S |
|
UNC Neuroscience Center, University of North Carolina, Chapel Hill, NC 27599, USA. |
| Brotman SM |
|
Brotman |
Sarah M |
SM |
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UNC Neuroscience Center, University of North Carolina, Chapel Hill, NC 27599, USA. |
| Thompson PM |
|
Thompson |
Paul M |
PM |
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Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA 90292, USA. |
| Medland SE |
|
Medland |
Sarah E |
SE |
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Psychiatric Genetics, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia. |
| Macciardi F |
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Macciardi |
Fabio |
F |
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Department of Psychiatry and Human Behavior, University of California, Irvine, CA 92697, USA. |
| Stranger BE |
|
Stranger |
Barbara E |
BE |
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Department of Pharmacology, Center for Genetic Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA. |
| Davis LK |
|
Davis |
Lea K |
LK |
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Vanderbilt University Medical Center, Vanderbilt Genetics Institute, Nashville, TN 37232, USA. |
| Fisher SE |
|
Fisher |
Simon E |
SE |
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Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, 6500 HB, Netherlands. |
| Stein JL |
|
Stein |
Jason L |
JL |
|
UNC Neuroscience Center, University of North Carolina, Chapel Hill, NC 27599, USA. |
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| INVESTIGATORS |
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| JOURNAL |
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| VOLUME: 31 |
| ISSUE: 4 |
| TITLE: Cerebral cortex (New York, N.Y. : 1991) |
| ISOABBREVIATION: Cereb Cortex |
| YEAR: 2021 |
| MONTH: Mar |
| DAY: 05 |
| MEDLINEDATE: |
| SEASON: |
| CITEDMEDIUM: Internet |
| ISSN: 1460-2199 |
| ISSNTYPE: Electronic |
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| MEDLINE JOURNAL |
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| MEDLINETA: Cereb Cortex |
| COUNTRY: United States |
| ISSNLINKING: 1047-3211 |
| NLMUNIQUEID: 9110718 |
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| PUBLICATION TYPE |
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| PUBLICATIONTYPE TEXT |
| Journal Article |
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| COMMENTS AND CORRECTIONS |
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| GRANTS |
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| GENERAL NOTE |
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| KEYWORDS |
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| KEYWORD |
| cortical surface area |
| genome-wide association study |
| human gained enhancers |
| polygenic selection |
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| MESH HEADINGS |
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| SUPPLEMENTARY MESH |
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| GENE SYMBOLS |
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| CHEMICALS |
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