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Genes related to sex steroids, neural growth, and social–emotional behavior are associated with autistic traits, empathy, and Asperger syndrome
Article first published online: 13 JUL 2009
DOI: 10.1002/aur.80
Copyright © 2009, International Society for Autism Research, Wiley Periodicals, Inc.
Additional Information
How to Cite
Chakrabarti, B., Dudbridge, F., Kent, L., Wheelwright, S., Hill-Cawthorne, G., Allison, C., Banerjee-Basu, S. and Baron-Cohen, S. (2009), Genes related to sex steroids, neural growth, and social–emotional behavior are associated with autistic traits, empathy, and Asperger syndrome. Autism Res, 2: 157–177. doi: 10.1002/aur.80
Publication History
- Issue published online: 16 JUL 2009
- Article first published online: 13 JUL 2009
- Manuscript Accepted: 26 MAY 2009
- Manuscript Revised: 20 MAY 2009
- Manuscript Received: 2 SEP 2008
Funded by
- Target Autism Genome (TAG)
- Nancy Lurie Marks (NLM) Family Foundation
- Elizabeth Rausing Family Trust
- Medical Research Council, UK, and ENSACP (N-EURO)
References
- , & (2008). Advances in autism genetics: on the threshold of a new neurobiology. Nature Review Genetics, 9, 341–355.
- AGP. (2007). Mapping autism risk loci using genetic linkage and chromosomal rearrangements. Nature Genetics, 39, 319–328.
- APA. (1994). DSM-IV diagnostic and statistical manual of mental disorders, 4th Edition. Washington, DC: American Psychiatric Association.
- , , , , , et al. (2006). An analysis paradigm for investigating multi-locus effects in complex disease: examination of three GABA A receptor subunit genes on 15q11–q13 as risk factors for autistic disorder. Annals of Human Genetics, 70, 281–292.
- , , , , , & (2006). Foetal testosterone and the child systemizing quotient. European Journal of Endocrinology, 155, 123–130.
- , , , , , & (2009). Fetal testosterone and autistic traits. British Journal of Psychology, 100, 1–22.
- , , , , , et al. (1995). Autism as a strongly genetic disorder: evidence from a British twin study. Psychological Medicine, 25, 63–77.
- , , , , , et al. (2006). Prevalence of disorders of the autism spectrum in a population cohort of children in South Thames: the Special Needs and Autism Project (SNAP). The Lancet, 368, 210–215.
- . (1995). Mindblindness: an essay on autism and theory of mind. Boston: MIT Press/Bradford Books.
- , & (1997). Parents of children with Asperger syndrome: what is the cognitive phenotype? Journal of Cognitive Neuroscience, 9, 548–554.
- , & (2004). The empathy quotient (EQ). An investigation of adults with Asperger syndrome or high functioning autism, and normal sex differences. Journal of Autism and Developmental Disorders, 34, 163–175.
- , , , & (1997). Another advanced test of theory of mind: evidence from very high functioning adults with autism or Asperger Syndrome. Journal of Child Psychology and Psychiatry, 38, 813–822.
- , , , , , & (2000). The amygdala theory of autism. Neuroscience and Behavioural Reviews, 24, 355–364.
- , , , , & (2001a). The “reading the mind in the eyes” test revised version: a study with normal adults, and adults with Asperger syndrome or high-functioning autism. Journal of Child Psychiatry and Psychiatry, 42, 241–252.
- , , , , & (2001b). The Autism Spectrum Quotient (AQ): evidence from Asperger syndrome/high functioning autism, males and females, scientists and mathematicians. Journal of Autism and Developmental Disorders, 31, 5–17.
- , , & . (2004). Prenatal testosterone in mind: amniotic fluid studies. Cambridge, MA: MIT/Bradford.
- , , & (2005). Sex differences in the brain: implications for explaining autism. Science, 310, 819–823.
- , , , , , & (2004). Autism and abnormal development of brain connectivity. Journal of Neuroscience, 24, 9228–9231.
- , , , , , et al. (2005). Support for the homeobox transcription factor gene engrailed 2 as an autism spectrum disorder susceptibility locus. American Journal of Human Genetics, 77, 851–868.
- , , & (2007). Cognitive style predicts entry into physical sciences and humanities: questionnaire and performance tests of empathy and systemizing. Learning and Individual Differences, 17, 260–268.
- , , , , , & (2004). Using self-report to identify the broad phenotype in parents of children with autistic spectrum disorders: a study using the Autism Spectrum Quotient. Journal of Child Psychology and Psychiatry, 45, 1431–1436.
- , , , , , et al. (2002). Association between a GABRB3 polymorphism and autism. Molecular Psychiatry, 7, 311–316.
- , , , , & (2006). Variations in human cannabinoid receptor (CNR1) gene modulate striatal response to happy faces. European Journal of Neuroscience, 23, 1944–1948.
- , , , , , & (2006). Maternal care associated with methylation of the estrogen receptor-alpha1b promoter and estrogen receptor-alpha expression in the medial preoptic area of female offspring. Endocrinology, 147, 2909–2915.
- , , , , , & (2006). Foetal testosterone and empathy: evidence from the empathy quotient (EQ) and the “reading the mind in the eyes test”. Social Neuroscience, 1, 135–148.
- , , & (1997). Variations on a theme: cataloging human DNA sequence variation. Science, 278, 1580–1581.
- , & (1998). Dehydroepiandrosterone: a potential signalling molecule for neocortical organisation during development. Proceedings of National Academy of Science USA, 95, 4678–4683.
- , , , , , et al. (2004). Association between the HOXA1 A218G polymorphism and increased head circumference in patients with autism. Biological Psychiatry, 55, 413–419.
- , & (2005). Intergenerational transmission of subthreshold autistic traits in the general population. Biological Psychiatry, 57, 655–660.
- , , , , , & (2002). Neural correlates of face and object recognition in young children with autism spectrum disorder, developmental delay and typical development. Child Development, 73, 700–717.
- , , , , & (2005). Asymmetric membrane ganglioside sialidase activity specifies axonal fate. Nature Neuroscience, 8, 544–546.
- , , , , , et al. (2002). A model system for study of sex chromosome effects on sexually dimorphic neural and behavioural traits. The Journal of Neuroscience, 22, 9005–9014.
- , , , , & (2007). Gabrb3 gene deficient mice exhibit impaired social and exploratory behaviors, deficits in non-selective attention and hypoplasia of cerebellar vermal lobules: a potential model of autism spectrum disorder. Behavioural Brain Research, 187, 207–220.
- , , , & (2003). Sexually dimorphic gene expression in mouse brain precedes gonadal differentiation. Molecular Brain Research, 118, 82–90.
- (2007). Development of cortical GABAergic circuits and its implications for neurodevelopmental disorders. Clinical Genetics, 72, 1–8.
- , , , & (2004). Mindreading difficulties in the siblings of people with Asperger's syndrome: evidence for a genetic influence in the abnormal development of a specific cognitive domain. Journal of Child Psychology and Psychiatry, 45, 412–418.
- , , , , & (2007). Oxytocin improves mindreading in humans. Biological Psychiatry, 61, 731–733.
- (2008). Likelihood-based association analysis for nuclear families and unrelated subjects with missing genotype data. Human Heredity, 66, 89–98.
- (2008). Controlling false discoveries in genetic studies. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 147B, 637–644.
- , & (2003). A review of 25 years of the social interaction test. European Journal of Pharmacology, 463, 35–53.
- . (1991). Clinical and neurobiological aspects of Asperger syndrome in six family studies. In: Frith, U., editor. Autism and Asperger syndrome. Cambridge: Cambridge University Press.
- , , , , , et al. (2003). Dosage-sensitive X-linked locus influences the development of amygdala and obitofrontal cortex, and fear recognition in humans. Brain, 126, 1–16.
- , , , , , et al. (1997). Increased stress response and bold beta-phenylethylamine in MAOB-deficient mice. Nature Genetics, 17, 206–210.
- , & (2003). Organizational effects of testosterone, estradiol, and dihydrotestosterone on vasopressin mRNA expression in the bed nucleus of the stria terminalis. Journal of Neurobiology, 54, 502–510.
- , , , & (2007). Heritability of autistic traits in the general population. Archives of Pediatric and Adolescent Medicine, 161, 372–377.
- , , , , , et al. (2003). Oxytocin infusion reduces repetitive behaviors in adults with autistic and Asperger's disorders. Neuropsychopharmacology, 28, 193–198.
- , , , , , , et al. (2009). Gene expression profiling of lymphoblasts from autistic and nonaffected sib pairs: altered pathways in neuronal development and steroid biosynthesis. PLoS ONE, 4, e5775.
- ICD-10. 1994. International classification of diseases. Geneva, Switzerland: World Health Organisation.
- ICD-10. 1994. International classification of diseases. Geneva, Switzerland: World Health Organisation.
- , , , & (2007). Elevated rates of testosterone-related disorders in women with autism spectrum conditions. Hormones and Behavior, 51, 597–604.
- , , & (1999). Oxytocin, vasopressin, and autism: is there a connection? Biological Psychiatry, 45, 145–157.
- , , , et al. (2003). Mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are associated with autism. Nature, 34, 27–29.
- , & (1997). Are people with autism or Asperger's syndrome faster than normal on the embedded figures task? Journal of Child Psychology and Psychiatry, 38, 527–534.
- , , , & (2005). Foetal testosterone, social cognition, and restricted interests in children. Journal of Child Psychology and Psychiatry, 46, 198–210.
- , , , , , et al. (2004). Polymorphisms in wolframin (WFS1) gene are possibly related to increased risk for mood disorders. The International Journal of Neuropsychopharmacology, 8, 235–244.
- , , , , & (2005). Oxytocin increases trust in humans. Nature, 435, 673–676.
- , , , & (2005). A previously uncharacterized role for estrogen receptor {beta}: defeminization of male brain and behavior. Proceedings of the National Academy of Sciences USA, 102, 4608.
- , , , , , et al. (2005). Steroid 11-beta-hydroxylase deficiency caused by compound heterozygosity for a novel mutation, p G314R, in one CYP11B1 allele, and a chimeric CYP11B2/CYP11B1 in the other allele. Hormone Research, 63, 284–293.
- , , & (1993). Usefulness of twin studies for exploring the etiology of childhood and adolescent psychiatric disorders. American Journal of Medical Genetics, 48, 47–59.
- , , , , & (2004). Measuring empathy—reliability and validity of the empathy quotient. Psychological Medicine, 34, 911–919.
- , , , & (2004). MAO-B knockout mice exhibit deficient habituation of locomotor activity but normal nicotine intake. Genes, Brain and Behavior, 3, 216–227.
- , & (2007). Social-cognition and the broad autism phenotype: identifying genetically meaningful phenotypes. Journal of Child Psychology and Psychiatry, 48, 105–112.
- , , & (2005). Glutamate and GABA signalling in the developing brain. Neuroscience, 130, 567–580.
- , , , & (2004). Maternal 2nd to 4th digit ratios and foetal testosterone. Early Human Development, 77, 23–28.
- , , , , & (2000). The role of ARNT2 in tumor angiogenesis and the neural response to hypoxia. Biochemical and Biophysical Research Communications, 273, 231–238.
- , , , , & (2000). ARNT2 acts as the dimerization partner of SIM1 for the development of the hypothalamus. Mechanisms of Development, 90, 253–261.
- (2003). Arguments for rejecting the sequential Bonferroni in ecological studies. Oikos, 100, 403–405.
- , , , , , et al. (2007). HOXA1 gene variants influence head growth rates in humans. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics 144B, 388–390.
- , , , , , et al. (2007). PLINK: a toolset for whole-genome association and population-based linkage analysis. American Journal of Human Genetics, 81, 559–575.
- , & (2005). Oestrogen and testosterone modulate the firing activity of dorsal raphe nucleus serotonergic neurones in both male and female rats. Journal of Neuroendocrinology, 17, 179–185.
- , , , , & (2003). Dendritic growth and spine formation in response to estrogen in the developing Purkinje cell. Endocrinology, 144, 4466–4477.
- , , & (2001). Nerve growth factor signaling, neuroprotection, and neural repair. Annual Review of Neuroscience, 24, 1217–1281.
- , , & (1994). Estrogen differentially regulates estrogen and nerve growth factor receptor mRNAs in adult sensory neuron. Journal of Neuroscience, 14, 459–471.
- , , , , , & (2005). Genetic investigation of quantitative traits related to autism: use of multivariate polygenic models with ascertainment adjustment. The American Journal of Human Genetics, 76, 68–81.
- , , & (2006). Are autistic traits an independent personality dimension? A study of the Autism Spectrum Quotient (AQ) and the NEO-PI-R. Personality and Individual Differences, 41, 873–883.
- . 1988. The autistic continuum. In: Wing, L., editor. Aspects of autism: biological research. London: Gaskell/Royal College of Psychiatrists.
- , , , & (2005). Screening adults for Asperger syndrome using the AQ: a preliminary study of its diagnostic validity in clinical practice. Journal of Autism and Developmental Disorders, 35, 331–335.
- , , , , , et al. (2005). Positive association of the oxytocin receptor gene (OXTR) with autism in the Chinese Han population. Biological Psychiatry, 58, 74–77.
- , , , , , et al. (2005). Analysis of the neuroligin 3 and 4 genes in autism and other neuropsychiatric patients. Molecular Psychiatry, 10, 329–332.
- , , , , , et al. (2004). Genome-wide scan for loci of Asperger syndrome. Mol Psychiatry, 9, 161–168.
- , , & (1992). The development of empathy in twins. Developmental Psychology, 28, 1038–1047.

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