title: Further investigations of the relation between polymorphisms in sex steroid related genes and autistic-like traits.
abstract: Autism spectrum disorders (ASDs) are more prevalent in boys than in girls, indicating that high levels of testosterone during early development may be a risk factor. Evidence for this hypothesis comes from studies showing associations between fetal testosterone levels, as well as indirect measures of prenatal androgenization, and ASDs and autistic-like traits (ALTs). In a recent study we reported associations between ALTs and single nucleotide polymorphisms (SNPs) in the genes encoding estrogen receptor 1 (ESR1), steroid-5-alpha-reductase, type 2 (SRD5A2) and sex hormone-binding globulin (SHBG) in a subset (n=1771) from the Child and Adolescent Twin Study in Sweden (CATSS). The aim of the present study was to try to replicate these findings in an additional, larger, sample of individuals from the CATSS (n=10,654), as well as to analyze additional SNPs of functional importance in SHBG and SRD5A2. No associations between the previously associated SNPs in the genes ESR1 and SRD5A2 and ALTs could be seen in the large replication sample. Still, our results show that two non-linked SNPs (rs6259 and rs9901675) at the SHBG gene locus might be of importance for language impairment problems in boys. The results of the present study do not point toward a major role for the investigated SNPs in the genes ESR1 and SRD5A2 in ALTs, but a possible influence of genetic variation in SHBG, especially for language impairment problems in boys, cannot be ruled out.
authors.affiliation: Institute of Neuroscience and Physiology, Department of Pharmacology, University of Gothenburg, Sweden; Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, University of Gothenburg, Sweden. Electronic address: anna.zettergren@neuro.gu.se.
authors.forename: Anna
authors.initials: A
authors.lastname: Zettergren
authors.affiliation: Institute of Neuroscience and Physiology, Department of Pharmacology, University of Gothenburg, Sweden.
authors.forename: Sara
authors.initials: S
authors.lastname: Karlsson
authors.affiliation: Institute of Neuroscience and Physiology, Department of Pharmacology, University of Gothenburg, Sweden.
authors.forename: Daniel
authors.initials: D
authors.lastname: Hovey
authors.affiliation: Institute of Neuroscience and Physiology, Department of Pharmacology, University of Gothenburg, Sweden.
authors.forename: Lina
authors.initials: L
authors.lastname: Jonsson
authors.affiliation: Institute of Neuroscience and Physiology, Department of Pharmacology, University of Gothenburg, Sweden.
authors.forename: Jonas
authors.initials: J
authors.lastname: Melke
authors.affiliation: Institute of Neuroscience and Physiology, Centre of Ethics, Law and Mental Health (CELAM), University of Gothenburg, Sweden.
authors.forename: Henrik
authors.initials: H
authors.lastname: Anckarsäter
authors.affiliation: Karolinska Institutet, Department of Medical Epidemiology and Biostatistics, Stockholm, Sweden.
authors.forename: Paul
authors.initials: P
authors.lastname: Lichtenstein
authors.affiliation: Institute of Neuroscience and Physiology, Centre of Ethics, Law and Mental Health (CELAM), University of Gothenburg, Sweden; Institute of Neuroscience and Physiology, Gillberg Neuropsychiatry Centre, University of Gothenburg, Sweden.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Lundström
authors.affiliation: Institute of Neuroscience and Physiology, Department of Pharmacology, University of Gothenburg, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Westberg
mesh_terms: D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D000293:Adolescent; D000067877:Autism Spectrum Disorder / Q000235:genetics* / Q000378:metabolism; D002648:Child; D047628:Estrogen Receptor alpha / Q000235:genetics* / Q000378:metabolism; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D008565:Membrane Proteins; D011956:Receptors, Cell Surface; C063572:sex hormone-binding globulin receptor; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; C548468:SRD5A2 protein, human
keywords: Association; Autism spectrum disorders; Autistic-like traits; Gene; Polymorphism; Sex steroids