Corpus Callosum Central Volume
Introduction
Background and Biological Basis
The corpus callosum is the largest white matter structure in the human brain, composed of millions of nerve fibers that connect the two cerebral hemispheres. This crucial commissure facilitates the transfer of information and coordination between the left and right sides of the brain, underpinning various cognitive and motor functions. The "central volume" refers to a specific quantitative measurement of this structure, typically obtained through neuroimaging techniques like Magnetic Resonance Imaging (MRI). Variations in the size and integrity of the corpus callosum can reflect individual differences in brain development, structure, and overall neural connectivity. The volume of various brain structures, including the corpus callosum, is a highly heritable trait, indicating a significant genetic influence on its size and morphology. [1]
Clinical Relevance
Alterations in corpus callosum volume have been observed in connection with a range of neurological and psychiatric conditions. Changes in brain structure, often assessed via MRI atrophy measures, are key indicators in neurodegenerative diseases such as Alzheimer's disease, where they serve as quantitative traits in genetic association studies. [2] As a major white matter tract, the corpus callosum is integral to brain connectivity, and its volume changes can be relevant to understanding the progression or risk of such neurological disorders. [3] Research aims to identify genetic variants, such as single nucleotide polymorphisms (SNPs), that are associated with these volumetric differences, potentially serving as biomarkers for disease susceptibility or progression.
Social Importance
Understanding the factors that influence corpus callosum central volume is of significant social importance. Given its critical role in interhemispheric communication, variations in its size may correlate with differences in cognitive abilities and overall neurological health across individuals. [1] Genome-wide association studies (GWAS) investigating brain volumes aim to uncover the biological underpinnings of complex traits and diseases. [4] Identifying these genetic links can contribute to earlier diagnosis, personalized treatment strategies, and a deeper understanding of brain development and aging processes. The ability to connect specific genetic markers to measurable brain structures like the corpus callosum central volume offers promising avenues for predictive medicine and interventions aimed at maintaining cognitive function and mitigating the impact of neurodegenerative conditions. [1]
Methodological and Statistical Considerations
Many genetic studies, while employing large meta-analyses to enhance statistical power, acknowledge that individual cohorts often do not achieve genome-wide significance, indicating a need for even larger sample sizes for definitive validation. [1] The statistical significance of findings for corpus callosum central volume can be influenced by the number of subjects within specific subgroups, even if the underlying genetic effect sizes remain consistent. [1] This suggests that some genuine genetic associations with corpus callosum central volume may remain undetected due to insufficient power or require more extensive replication efforts. Furthermore, while initial discovery phases may use less stringent significance thresholds to identify candidate variants, these findings do not constitute genome-wide significance until successfully replicated at more rigorous statistical levels. [1]
Even with robust replication, the proportion of variance in brain volumes explained by individual common genetic variants is often small, typically ranging from 1% to 3%. [5] While this is comparable to effect sizes observed for other complex traits, it implies that a substantial portion of the variability in corpus callosum central volume remains unexplained by the specific common genetic variants currently identified. [5] The absence of replication for a particular genetic association could indicate either a true negative result or an effect that is specific to certain age groups or cohorts, highlighting the complexity of genetic influences on brain structure. [1]
Generalizability and Phenotype Definition
Current genetic studies frequently rely on imputation panels derived primarily from populations like HapMap CEU, which predominantly represent individuals of European descent. [6] This reliance inherently limits the generalizability of findings concerning corpus callosum central volume to diverse ancestral and ethnic groups, necessitating further research in more varied global populations. Additionally, the inclusion of cohorts spanning different stages of life suggests that genetic effects on brain structures may not be uniform across the lifespan, meaning identified associations might be age-specific rather than universally applicable. [1]
Differences in MRI post-processing algorithms and software used across various studies, despite being validated against manual tracings, can introduce subtle heterogeneity in volume measurements. [7] While such differences might primarily lead to reduced statistical power and false negatives, they can complicate the precise quantification of corpus callosum central volume across studies. A significant methodological consideration is the approach to correcting for overall head size; expressing brain volumes as a percentage of intracranial volume can substantially attenuate correlations with absolute intracranial volume, potentially altering the interpretation of genetic associations. [7] This raises questions about whether identified genetic variants influence corpus callosum central volume directly or if their effects are mediated through an influence on overall brain size, particularly since regional brain volumes are often affected by global brain dimensions in a potentially non-linear manner. [8]
Mechanistic Insights and Unexplained Heritability
While genetic associations with corpus callosum central volume can be identified, existing studies often lack the direct mechanistic evidence needed to explain how specific single nucleotide variations translate into observable structural differences in the brain. [1] A comprehensive understanding would require integrating data on gene expression, protein function, and the intricate biological pathways downstream of identified variants, which is typically beyond the scope of initial genome-wide association studies. [1] Consequently, the precise pathophysiological relevance of many identified genetic factors for corpus callosum central volume remains to be fully elucidated, representing a significant knowledge gap.
The relatively small proportion of variance explained by individual common genetic variants suggests that a substantial part of the heritability of corpus callosum central volume, often referred to as 'missing heritability', remains unaccounted for. [5] This unexplained variance could stem from numerous factors not comprehensively captured by current GWAS designs, including the cumulative effects of many variants with individually minute effects, rare genetic variants, gene-environment interactions, or epigenetic modifications. [5] Therefore, while common variants provide initial insights, a more holistic understanding of the complex genetic architecture and environmental contributions to corpus callosum central volume is still an evolving area of research.
Variants
Genetic variations play a crucial role in shaping brain morphology and connectivity, including the corpus callosum central volume, which is essential for interhemispheric communication. Multiple single nucleotide polymorphisms (SNPs) and their associated genes have been implicated in influencing various brain structures. The corpus callosum, a large white matter tract, undergoes significant development and remodeling throughout life, making it susceptible to genetic influences on its size and integrity . [3], [9]
Genes involved in neural development and cell signaling pathways are particularly relevant. For instance, _JAG1_ encodes Jagged 1, a ligand for Notch receptors, critical for cell fate determination, differentiation, and neurogenesis during embryonic development. Variants like rs1883801 in or near _JAG1_ could subtly alter Notch signaling, potentially impacting the formation or myelination of callosal axons. Similarly, _LNX1_, or Ligand of Numb Protein X 1, is known to regulate the Notch pathway by mediating ubiquitination of Notch receptors and other proteins, thereby influencing cell differentiation and neuronal development. [8] A variant such as rs7673075, linked to _LNX1_ and _RPL21P44_, might affect the precision of neuronal connectivity or axonal guidance, which are vital for establishing the intricate structure of the corpus callosum. Additionally, _MLLT10_ (Mixed-Lineage Leukemia Translocation 10) is a gene involved in chromatin remodeling and gene expression regulation, crucial for proper cellular development and differentiation. A variant like rs12251016 could modulate these epigenetic processes, potentially affecting the developmental trajectory of brain structures, including the corpus callosum. [10]
Other variants are associated with genes that play roles in general cellular health, growth regulation, and stress responses, which are indirectly vital for brain structure. _NUAK1_ (NUAK family kinase 1) is involved in cell adhesion, cell cycle control, and cellular responses to stress, processes fundamental for neuronal survival and plasticity. A variant like rs12146713 could alter _NUAK1_ activity, potentially affecting the maintenance of neural networks or the response of brain cells to environmental cues. _DUSP8_ (Dual Specificity Phosphatase 8) is a phosphatase that regulates critical MAPK signaling pathways, which are essential for cell growth, differentiation, and stress responses within the brain. The rs7933575 variant might influence this regulatory balance, impacting the overall cellular environment necessary for healthy brain development and maintenance. [11] Furthermore, _GMNC_ (Geminin C) is involved in DNA replication and cell cycle progression, which are fundamental processes for neural progenitor proliferation during brain development. Alterations associated with variants such as rs773198357 or rs7616662 within _GMNC_ or _OSTN_ (Osteonectin), a gene involved in cell-matrix interactions and tissue remodeling, could impact the number of cells contributing to brain tissue or their organization, thereby influencing the overall volume of structures like the corpus callosum. [7]
Additional genes and their variants contribute to the complex genetic landscape influencing brain traits. _IL11_ (Interleukin 11), a cytokine, is involved in cell growth and differentiation, and could play a role in neuroinflammation or supportive cell functions in the brain. The variant rs35791293, associated with _IL11_ and _TMEM190_ (Transmembrane Protein 190), might affect these broader cellular communications. _STRN_ (Striatin) is a scaffolding protein that participates in various signaling pathways, neuronal plasticity, and the organization of the cytoskeleton, which is crucial for neuronal shape and function. A variant like rs11124554 could modify _STRN_'s ability to coordinate these cellular processes, potentially influencing the structural integrity of neurons and their connections. _AMZ2P1_ (Amidohydrolase 2 Pseudogene 1) is a pseudogene, which can sometimes regulate nearby functional genes or produce non-coding RNAs, subtly impacting cellular processes, while _C16orf95_ (Chromosome 16 Open Reading Frame 95) is a less characterized gene, but any gene expressed in the brain holds potential to influence its development or ongoing function. [12] The variant rs62072157 linked to _AMZ2P1_ and rs4843560 for _C16orf95_ highlight the broad genetic underpinnings of complex brain traits, where even genes with less defined roles can contribute to the overall variability in brain structure and function, including corpus callosum central volume. [6]
Key Variants
| RS ID | Gene | Related Traits |
|---|---|---|
| rs773198357 rs7616662 |
GMNC - OSTN | corpus callosum central volume corpus callosum volume |
| rs12146713 | NUAK1 | cerebral cortex area attribute cortical thickness brain connectivity attribute thalamus volume white matter microstructure measurement |
| rs35791293 | IL11 - TMEM190 | blood protein amount corpus callosum central volume corpus callosum volume |
| rs11124554 | STRN | serum alanine aminotransferase amount heart failure corpus callosum central volume |
| rs1883801 | JAG1 | cortical thickness eosinophil count corpus callosum central volume rostrum of corpus callosum volume corpus callosum volume |
| rs62072157 | AMZ2P1, AMZ2P1 | white matter microstructure measurement corpus callosum central volume rostrum of corpus callosum volume corpus callosum volume |
| rs4843560 | C16orf95 | cerebral cortex area attribute white matter microstructure measurement brain volume cerebral cortex area attribute, neuroimaging measurement corpus callosum central volume |
| rs7673075 | LNX1 - RPL21P44 | genu of corpus callosum volume corpus callosum central volume corpus callosum volume |
| rs7933575 | DUSP8 | genu of corpus callosum volume corpus callosum central volume |
| rs12251016 | MLLT10 | body mass index brain connectivity attribute brain attribute insomnia insomnia measurement |
Definition and Neuroanatomical Context
The corpus callosum is the largest commissural fiber tract in the human brain, serving as the primary connection between the two cerebral hemispheres. It facilitates interhemispheric communication, playing a crucial role in various cognitive functions and the integration of sensory, motor, and cognitive information. "Corpus callosum central volume" refers to a quantitative measure of the size of this white matter structure, typically assessed through neuroimaging techniques. [3] The measurement of its volume is integral to understanding brain morphology and its alterations across development, aging, and neurological conditions. Changes in corpus callosum volume can reflect underlying neurobiological processes, including development, degeneration, and the impact of various disorders.
Measurement Methodologies and Normalization
The operational definition of corpus callosum central volume involves its quantification from high-resolution structural magnetic resonance imaging (MRI) scans. Advanced automated segmentation algorithms, such as those implemented in software packages like FreeSurfer and FMRIB's Integrated Registration and Segmentation Tool (FIRST) from the FMRIB Software Library (FSL), are commonly employed for delineating brain structures and calculating their volumes. [12] These algorithms use sophisticated procedures including nonbrain tissue removal, automated Talairach transformation, intensity normalization, and surface deformation to accurately segment white matter and deep gray matter structures. [2] To account for individual differences in overall head size, which can confound comparisons of brain region volumes, corpus callosum central volume is typically normalized by the subject's intracranial volume (ICV). [2] This normalization process ensures that observed volumetric differences are more likely to reflect specific brain structure variations rather than general head size variations. [4]
Quantitative Trait and Clinical Relevance
Corpus callosum central volume is often treated as a quantitative trait in research studies, allowing for the investigation of its genetic determinants and its associations with various phenotypic characteristics. The use of continuous traits like brain volumes, rather than discrete diagnostic categories, can provide greater power to detect genetic influences and may better reflect underlying biology. [8] Such volumetric measures are highly reproducible, demonstrating high intraclass correlation coefficients (ICCs) in test-retest scenarios, which underscores their reliability for research applications. [1] Understanding the factors that influence corpus callosum central volume can provide insights into the neurobiology of disorders, potentially leading to improved diagnostic criteria and the identification of new treatment targets. [12] Its assessment is significant in studies exploring brain development, neurodegeneration (such as in Alzheimer's disease), and other neuropsychiatric disorders. [8]
Causes of Corpus Callosum Central Volume
The corpus callosum, a crucial commissural pathway connecting the cerebral hemispheres, exhibits variations in its central volume that are influenced by a complex interplay of genetic, developmental, and broader physiological factors. Understanding these causal elements is essential for elucidating brain health and neurological conditions.
Genetic Foundations of Brain Structure
Genetic factors play a significant role in determining brain volumes, including those that might influence the corpus callosum. Studies indicate that overall brain and intracranial volumes are highly heritable, suggesting a substantial genetic contribution to individual differences in brain size. [1] Specific genetic variants have been associated with various brain regions, providing insights into potential influences on corpus callosum central volume. For instance, common variants at 6q22 and 17q21 have been linked to intracranial volume, with rs4273712 on chromosome 6 near RSPO3 and RNF146 identified as potentially relevant to neuronal development. [7] Similarly, the C allele of rs10784502 is associated with larger intracranial volume. [1] While these findings directly relate to overall head or brain size, the relationship between corpus callosum size and forebrain volume suggests that genetic factors influencing general brain dimensions likely also contribute to the central volume of the corpus callosum. [9] Other genetic loci, such as those within the PICALM gene (e.g., rs642949) associated with cortical thickness, or the FMO gene cluster on chromosome 1 linked to lentiform nucleus volume, highlight a polygenic architecture where numerous common variants, each with small effects, collectively influence brain morphology. [2]
Developmental Trajectories and Lifespan Dynamics
The central volume of the corpus callosum is not static but undergoes significant changes throughout development and across the lifespan. Its structural alterations are mapped during periods of both brain development and degeneration. [3] Early life developmental processes are critical for the formation and maturation of this white matter tract, influencing its ultimate size and integrity. As individuals age, the brain experiences natural degenerative processes that can lead to changes in various brain volumes, including potentially the corpus callosum. Factors such as age and sex are known to have significant effects on brain region volumes, which are often controlled for in analyses of brain morphology. [5] The dynamic nature of the corpus callosum's structure from early life through senescence implies that a combination of genetically programmed developmental milestones and age-related changes are key determinants of its central volume.
Broader Neurological and Systemic Influences
Beyond genetics and typical development, various systemic conditions and external factors can modulate corpus callosum central volume. Neurological comorbidities and disease states are recognized as potential contributors to alterations in brain structure. Researchers often account for disease status as a covariate in studies, acknowledging its possible impact on brain volumetric measures. [2] Furthermore, the effects of medications can also influence brain volumes, necessitating careful consideration in research settings. While specific environmental factors such as diet or exposure are not extensively detailed regarding their direct impact on corpus callosum central volume in the provided research, studies do account for "altered environments and experiences" to ensure that observed genetic associations are not confounded by these broader influences, suggesting their potential, albeit indirect, role. [1]
Developmental Biology and Structural Connectivity
The corpus callosum, a crucial white matter tract, serves as the primary commissural pathway connecting the two cerebral hemispheres, facilitating interhemispheric communication. Its size is intricately linked to overall forebrain volume and the complex folding patterns of the human cerebral cortex. [9] This structural component undergoes significant alterations throughout brain development and during neurodegenerative processes, highlighting its dynamic nature and importance for brain function. [3] The development of brain structures, including the corpus callosum, is a prolonged process that begins in utero and continues through childhood into early adulthood, contributing significantly to the increasing intracranial volume. [7]
During this critical developmental period, mechanisms like corticogenesis, the formation of the cerebral cortex, are fundamental for establishing the brain's complex architecture. Genes such as TMSB4X are expressed in the brain and implicated in these developmental processes, including corticogenesis and actin polymerization, which are essential for neuronal migration and plasticity. [1] The final intracranial volume, largely determined by early brain growth, remains relatively stable throughout life, but brain volume itself begins to decline in later adulthood, particularly due to neurodegenerative conditions. [7]
Genetic Architecture of Brain Volume
The volumes of brain structures, including the corpus callosum, are highly heritable traits, with genetic factors explaining a substantial proportion of their variability, as observed for other brain regions like the lentiform nucleus where heritability can range from 70% to 80%. [4] Genome-wide association studies (GWAS) have been instrumental in identifying common genetic variants and specific genes that influence the size of various brain structures, including hippocampal and intracranial volumes. [1] These studies utilize statistical methods, such as gene-based tests, to combine association statistics and evaluate the cumulative evidence of genetic influence on phenotypes, often integrating with biological pathway databases to identify enriched disease and biological pathways. [4]
Genetic analyses have pinpointed specific genes and single nucleotide polymorphisms (SNPs) associated with brain volumes. For instance, a significant association has been found in and around the genes WDR41 and PDE8B, with variants like rs335636 located within a deletion region in the untranslated regions of both genes, suggesting functional relevance. [1] Other genes, such as DRD2, have been previously linked to variations in caudate volume and the availability of striatal dopamine D2 receptors. [13] Furthermore, PICALM, a gene associated with Alzheimer's disease risk, has been highlighted through SNP grouping and set-based analyses as influencing cortical thickness, indicating its broader impact on brain structure and neurodegeneration. [2] Genes like C10orf46 (also known as CAC1), characterized as a cell cycle-associated protein, and TMSB4X, involved with corticogenesis and actin polymerization, also represent candidates whose genetic variations could impact brain development and volume. [1]
Molecular and Cellular Underpinnings
The precise volume and integrity of brain structures like the corpus callosum are governed by complex molecular and cellular mechanisms. Key biomolecules, such as NMDA receptors, are integral components of neuronal signaling pathways and synaptic plasticity, playing critical roles in learning, memory, and overall brain function. [14] Variations in the expression or function of these receptors can impact neuronal health and connectivity, potentially influencing brain volumes. Similarly, dopamine D2 receptors, whose availability in the striatum can be affected by genetic variants, are crucial for modulating neural circuits involved in motor control, cognition, and reward, with implications for regional brain volumes. [13]
Beyond receptor-mediated signaling, other fundamental cellular processes contribute to brain structure. Proteins encoded by genes like C10orf46 (CAC1), which is involved in cell cycle regulation, play a role in neurogenesis and glial cell proliferation, thereby influencing tissue growth and maintenance. [1] Furthermore, the protein TMSB4X is critical for actin polymerization, a dynamic process essential for neuronal migration, axon guidance, and synaptic remodeling during brain development and throughout life. [1] Synaptic cell surface proteins, such as Neurexins, are also vital for establishing and maintaining synaptic connections, forming regulatory networks that are fundamental to the structural and functional integrity of the brain. [15] Disruptions in these molecular and cellular pathways can profoundly affect brain structure and volume.
Neurodegeneration and Pathophysiological Relevance
Alterations in the central volume of the corpus callosum are relevant to pathophysiological processes, particularly in the context of neurodegeneration. Structural changes in brain regions, including the corpus callosum, are observed during brain degeneration and are associated with neurodegenerative disorders such as Alzheimer's disease. [3] Brain volume typically begins to decrease after early adulthood, with accelerated loss occurring in advanced age due to polygenic and environmental influences, leading to brain atrophy. [7] This atrophy can be a hallmark of various neurodegenerative and cerebrovascular diseases, impacting overall cognitive ability and brain function. [7]
The genetic underpinnings of these structural alterations provide insights into disease mechanisms. For example, specific genetic variants, such as those in the PICALM gene, have been associated with both cortical thickness and an increased risk for Alzheimer's disease, highlighting how genetic factors can predispose individuals to neurodegenerative changes that affect brain volumes. [2] Understanding the biological mechanisms that influence corpus callosum central volume, from molecular pathways to genetic predispositions and their manifestation in developmental and degenerative processes, is crucial for unraveling the complex etiology of brain disorders and identifying potential therapeutic targets. [14]
Large-scale Cohort Studies and Imaging Methodologies
Population studies of brain morphology, including specific regional volumes, frequently leverage large-scale cohorts and biobank studies to investigate their genetic and environmental determinants. For instance, the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, which includes studies like AGES-Reykjavik, ARIC, FHS, and the Rotterdam Study (RS I, II, III), has been instrumental in pooling data from thousands of participants to enhance statistical power
Frequently Asked Questions About Corpus Callosum Central Volume
These questions address the most important and specific aspects of corpus callosum central volume based on current genetic research.
1. Will my brain size be like my parents'?"
Yes, your brain's structure, including the volume of important parts like the corpus callosum, is highly influenced by your genetics. This means you inherit many traits related to brain size and shape from your parents. While brain volumes in general are known to be highly heritable, other factors like your environment and lifestyle also play a role.
2. Why do some friends learn faster than me?"
It's possible that individual differences in brain structures, such as the corpus callosum's central volume, play a role in how efficiently information is processed. This structure is key for communication between brain hemispheres, which underpins various cognitive functions like learning. While genetics significantly influence these structural differences, they typically explain only a small portion (1-3%) of the variation. Many other factors, including your experiences and personal learning strategies, also contribute to how quickly you learn.
3. Does my brain volume mean I'll get Alzheimer's?"
Not necessarily, but changes in brain structure, including corpus callosum volume, are linked to neurodegenerative diseases like Alzheimer's. Research uses these volume changes as quantitative traits in genetic studies to identify risk factors. While identifying certain genetic variants associated with brain volume can help assess susceptibility, having a specific volume doesn't guarantee you'll develop the disease. It's more about understanding risk and progression.
4. Is it normal for my brain to shrink as I age?"
Yes, it is common for brain structures, including the corpus callosum, to show changes in volume over the lifespan. These age-related changes are relevant to understanding neurodegenerative conditions. Genetic effects on brain structures may not be uniform across your entire life, meaning some genetic associations could be age-specific. Regular monitoring through imaging can help track these changes.
5. Does my ethnic background affect my brain's connections?"
Yes, your ethnic background can be relevant because genetic studies on brain structures have primarily focused on populations of European descent. This means that findings might not fully apply to diverse ancestral and ethnic groups like yours, as different populations can have unique genetic risk factors. More research is needed across varied global populations to fully understand these differences.
6. Can exercise make my brain connections stronger?"
While the focus is often on genetics of brain volume, exercise is generally known to support overall brain health and connectivity. The corpus callosum itself is a major white matter tract, integral to brain connectivity. Maintaining a healthy lifestyle, which includes exercise, can contribute to the integrity of these crucial connections, even if direct genetic links to volume aren't fully understood mechanistically.
7. Why is my brain different from my sibling's?"
Even though brain volume is highly heritable, you and your sibling inherited slightly different combinations of genes from your parents. This genetic variation, combined with unique life experiences and environmental factors, can lead to differences in brain structure, including corpus callosum volume. Individual common genetic variants typically explain only a small portion (1-3%) of these differences.
8. Could a brain scan tell me about my future health?"
Yes, brain imaging like MRI can provide valuable insights into your brain's current structure, including corpus callosum volume. Researchers use these measurements as potential biomarkers to assess risk or progression of neurological disorders. While a scan can identify structural alterations, it's often combined with genetic information to offer a more complete picture of your future health susceptibility.
9. Can I change my brain's natural structure?"
Your brain's overall structure, including its volume, is highly influenced by genetics you inherit. However, while genetic factors set a baseline, environmental influences and lifestyle choices can also play a role in shaping brain health and connectivity over time. Research is still exploring the full extent to which interventions can modify specific brain volumes.
10. Does a 'smaller' brain mean I'm less smart?"
No, a 'smaller' corpus callosum central volume doesn't directly equate to being less intelligent. While variations in this structure can correlate with differences in cognitive abilities, overall brain size or the volume of a single structure isn't the sole determinant of intelligence. Cognitive function is complex, influenced by many brain regions, their connections, and individual experiences.
This FAQ was automatically generated based on current genetic research and may be updated as new information becomes available.
Disclaimer: This information is for educational purposes only and should not be used as a substitute for professional medical advice. Always consult with a healthcare provider for personalized medical guidance.
References
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[4] Hibar DP, et al. "Genome-wide association identifies genetic variants associated with lentiform nucleus volume in N = 1345 young and elderly subjects." Brain Imaging and Behavior, 2012.
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[6] Bis, J. C. et al. "Common variants at 12q14 and 12q24 are associated with hippocampal volume." Nat Genet, vol. 44, no. 5, 2012, pp. 545-551.
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[13] Bartres-Faz D, Junque C, Serra-Grabulosa JM, Lopez-Alomar A, Moya A, Bargallo N, et al. "Dopamine DRD2 Taq I polymorphism associates with caudate nucleus volume and cognitive performance in memory impaired subjects." Neuroreport, vol. 13, no. 9, 2002, pp. 1121–1125.
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[15] Ushkaryov YA, Petrenko AG, Geppert M, Sudhof TC. "Neurexins: synaptic cell surface proteins related to the alpha-latrotoxin receptor and laminin." Science, vol. 257, no. 5066, 1992, pp. 50–56.