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Common genetic variants influence human subcortical brain structures

Authors: Hibar, Derrek P; Stein, Jason L; Aribisala, Benjamin S; de Zubicaray, Greig I; Dillman, Allissa; Duggirala, Ravi; Dyer, Thomas D; +241 Authors

Common genetic variants influence human subcortical brain structures

Abstract

Contains fulltext : 144426.pdf (Publisher’s version ) (Closed access) Contains fulltext : 144426pre.pdf (Author’s version preprint ) (Open Access) The highly complex structure of the human brain is strongly shaped by genetic influences. Subcortical brain regions form circuits with cortical areas to coordinate movement, learning, memory and motivation, and altered circuits can lead to abnormal behaviour and disease. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume and intracranial volume. These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08 x 10(-33); 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability in human brain development, and may help to determine mechanisms of neuropsychiatric dysfunction. 6 p.

Countries
Ireland, France, Netherlands, Netherlands, Netherlands, Netherlands, Netherlands, United Kingdom, Germany, Netherlands, Canada, Ireland, Netherlands, Netherlands, Italy, Netherlands, Netherlands, Netherlands, Netherlands, United Kingdom
Subjects by Vocabulary

Microsoft Academic Graph classification: Caudate nucleus Genome-wide association study Basal ganglia Neuroscience Striatum Hippocampal formation Genetics Putamen Human brain medicine.anatomical_structure Anatomy & histology Biology medicine

Dewey Decimal Classification: ddc:500

Keywords

Netherlands Twin Register (NTR), Male, Aging, human geography, SEGMENTATION, Apoptosis, Expression, 130 000 Cognitive Neurology & Memory, Hippocampal, Child, Aged, 80 and over, Putamen, Brain, Chromatin, genetics [Genetic Variation], Dynamics, disease incidence, Basal ganglia, Evolution, anatomy & histology [Hippocampus], Article, Striatum, SDG 3 - Good Health and Well-being, Humans, GENOME-WIDE ASSOCIATION, Kinectin, Aged, IDENTIFICATION, Skull, Genetic Variation, Genetic Loci, KTN1 protein, human, anatomy & histology [Brain], CHROMATIN, Identification, Hippocampus, BASAL GANGLIA, genetics [Gene Expression Regulation, Developmental], anatomy & histology [Skull], Sex Characteristics, KINECTIN, Genome-wide association, Multidisciplinary, Gene Expression Regulation, Developmental, blood; brain; disease incidence; genetic variation; human geography; neurology, Organ Size, Middle Aged, Magnetic Resonance Imaging, genetics [Membrane Proteins], genetics [Aging], [ SCCO.NEUR ] Cognitive science/Neuroscience, /dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being, Female, anatomy & histology [Caudate Nucleus], Neuroinformatics, EXPRESSION, Adult, Adolescent, ORGANIZATION, genetics [Genetic Loci], Young Adult, blood, /dk/atira/pure/keywords/cohort_studies/netherlands_twin_register_ntr_, Journal Article, General, genetics [Apoptosis], Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], HIPPOCAMPAL, genetics [Organ Size], neurology, [SCCO.NEUR]Cognitive science/Neuroscience, Membrane Proteins, NERVOUS-SYSTEM, anatomy & histology [Putamen], Caudate Nucleus, Genome-Wide Association Study

45 references, page 1 of 5

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2. Kravitz AV, et al. Regulation of parkinsonian motor behaviours by optogenetic control of basal ganglia circuitry. Nature. 2010; 466:622-626. [PubMed: 20613723]

3. Poldrack RA, et al. Interactive memory systems in the human brain. Nature. 2001; 414:546-550. [PubMed: 11734855] [OpenAIRE]

4. Pessiglione M, Seymour B, Flandin G, Dolan RJ, Frith CD. Dopamine-dependent prediction errors underpin reward-seeking behaviour in humans. Nature. 2006; 442:1042-1045. [PubMed: 16929307] [OpenAIRE]

5. Stein JL, et al. Identification of common variants associated with human hippocampal and intracranial volumes. Nature Genet. 2012; 44:552-561. [PubMed: 22504417] [OpenAIRE]

6. Ikram MA, et al. Common variants at 6q22 and 17q21 are associated with intracranial volume. Nature Genet. 2012; 44:539-544. [PubMed: 22504418]

7. Lango Allen H, et al. Hundreds of variants clustered in genomic loci and biological pathways affect human height. Nature. 2010; 467:832-838. [PubMed: 20881960] [OpenAIRE]

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    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
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    impulse
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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
views
OpenAIRE UsageCountsViews provided by UsageCounts
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750
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EC| MATRICS
Project
MATRICS
Multidisciplinary Approaches to Translational Research In Conduct Syndromes
  • Funder: European Commission (EC)
  • Project Code: 603016
  • Funding stream: FP7 | SP1 | HEALTH
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