Normal variation in fronto-occipital circuitry and cerebellar structure with an autism-associated polymorphism of CNTNAP2
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Recent genetic studies have implicated a number of candidate genes in the pathogenesis of Autism Spectrum Disorder (ASD). Polymorphisms of CNTNAP2 (contactin-associated like protein-2), a member of the neurexin family, have already been implicated as a susceptibility gene for autism by at least 3 separate studies. We investigated variation in white and grey matter morphology using structural MRI and diffusion tensor imaging. We compared volumetric differences in white and grey matter and fractional anisotropy values in control subjects characterised by genotype at rs7794745, a single nucleotide polymorphism in CNTNAP2. Homozygotes for the risk allele showed significant reductions in grey and white matter volume and fractional anisotropy in several regions that have already been implicated in ASD, including the cerebellum, fusiform gyrus, occipital and frontal cortices. Male homozygotes for the risk alleles showed greater reductions in grey matter in the right frontal pole and in FA in the right rostral fronto-occipital fasciculus compared to their female counterparts who showed greater reductions in FA of the anterior thalamic radiation. Thus a risk allele for autism results in significant cerebral morphological variation, despite the absence of overt symptoms or behavioural abnormalities. The results are consistent with accumulating evidence of CNTNAP2's function in neuronal development. The finding suggests the possibility that the heterogeneous manifestations of ASD can be aetiologically characterised into distinct subtypes through genetic-morphological analysis.
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Common variation in different ASD-associated CNTNAP2 SNPs modulates brain morphology in several ASD-related cortical regions in normal controls.
“Similarly, common variation in different ASD-associated CNTNAP2 single nucleotide polymorphism (SNP) [64], has been shown to modulate brain morphology in several ASD related cortical regions in normal controls [65].”
From Genetics of autism spectrum disorders (2011) · cites this paper as [65]
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- Authors
- Tan, G. C. Y., Doke, T. F., Ashburner, J., Wood, N. W., & Frackowiak, R. S. J.
- Affiliations
- Wellcome Centre for Human Neuroimaging (GB)
- UCL Queen Square Institute of Neurology (GB)
- Corresponding author
- Tan, Geoffrey C.Y.
- Venue
- NeuroImage
- Publisher
- Elsevier BV
- Published
- 2010-11
- Volume
- 53
- Issue
- 3
- Pages
- 1030-1042
- ISSN
- 1053-8119 (ISSN-L)
- PMC
- PMC2941042
- OpenAlex
- W2020960495
- Cited by
- 116
- References
- 86
- Citations by year
- 2025: 4 · 2024: 3 · 2023: 2 · 2022: 7 · 2021: 8 · 2020: 8 · 2019: 6 · 2018: 5 · 2017: 12 · 2016: 8 · 2015: 7 · 2014: 5 · 2013: 12 · 2012: 14
- FWCI
- 7.95
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- NeuroImage (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- SERVAL (Université de Lausanne) (publishedVersion, cc-by)
- IRIS (submittedVersion, cc-by)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Wellcome Trust (075696/Z/4/Z)
- Agency for Science, Technology and Research in Singapore
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- autism spectrum disorder, CNTNAP2, single nucleotide polymorphisms, genetic susceptibility, gray matter volume, fractional anisotropy, cerebellum, anterior thalamic radiation, fusiform gyrus, sex differences, neuroanatomical variation
- MeSH terms
- Cerebellum, Child, Child Development Disorders, Pervasive, Female, Frontal Lobe, Genotype, Humans, Image Interpretation, Computer-Assisted, Magnetic Resonance Imaging, Male, Membrane Proteins, Nerve Tissue Proteins, Neural Pathways, Occipital Lobe, Polymorphism, Restriction Fragment Length, Polymerase Chain Reaction, Anisotropy, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Endophenotypes
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