| 1. |
- Henningsson, Susanne, 1977, et al.
(författare)
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Possible association between the androgen receptor gene and autism spectrum disorder.
- 2009
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Ingår i: Psychoneuroendocrinology. - : Elsevier BV. - 0306-4530 .- 1873-3360. ; 34:5, s. 752-761
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Tidskriftsartikel (refereegranskat)abstract
- Autism is a highly heritable disorder but the specific genes involved remain largely unknown. The higher prevalence of autism in men than in women, in conjunction with a number of other observations, has led to the suggestion that prenatal brain exposure to androgens may be of importance for the development of this condition. Prompted by this hypothesis, we investigated the potential influence of variation in the androgen receptor (AR) gene on the susceptibility for autism. To this end, 267 subjects with autism spectrum disorder and 617 controls were genotyped for three polymorphisms in exon 1 of the AR gene: the CAG repeat, the GGN repeat and the rs6152 SNP. In addition, parents and affected siblings were genotyped for 118 and 32 of the cases, respectively. Case-control comparisons revealed higher prevalence of short CAG alleles as well as of the A allele of the rs6152 SNP in female cases than in controls, but revealed no significant differences with respect to the GGN repeat. Analysis of the 118 families using transmission disequilibrium test, on the other hand, suggested an association with the GGN polymorphism, the rare 20-repeat allele being undertransmitted to male cases and the 23-repeat allele being overtransmitted to female cases. Sequencing of the AR gene in 46 patients revealed no mutations or rare variants. The results lend some support for an influence of the studied polymorphisms on the susceptibility for autism, but argue against the possibility that mutations in the AR gene are common in subjects with this condition.
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| 2. |
- Hovey, Daniel, et al.
(författare)
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Antisocial behavior and polymorphisms in the oxytocin receptor gene: findings in two independent samples.
- 2016
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Ingår i: Molecular psychiatry. - Stockholm : Springer Science and Business Media LLC. - 1476-5578 .- 1359-4184. ; 16
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Tidskriftsartikel (refereegranskat)abstract
- The quantitative genetic contribution to antisocial behavior is well established, but few, if any, genetic variants are established as risk factors. Emerging evidence suggests that the neuropeptide oxytocin (OXT) may modulate interpersonal aggression. We here investigated whether single-nucleotide polymorphisms (SNPs) in the OXT receptor gene (OXTR) are associated with the expression of antisocial behavior. A discovery sample, including both sexes, was drawn from the Child and Adolescent Twin Study in Sweden (CATSS; n=2372), and a sample from the Twin Study of Child and Adolescent Development (TCHAD; n=1232) was used for replication. Eight SNPs in OXTR, selected on previous associations with social and antisocial behavior, were genotyped in the participants of CATSS. Significant polymorphisms were subsequently genotyped in TCHAD for replication. Participants completed self-assessment questionnaires-Life History of Aggression (LHA; available only in CATSS), and Self-Reported Delinquency (SRD; available in both samples)-designed to capture antisocial behavior as continuous traits. In the discovery sample, the rs7632287 AA genotype was associated with higher frequency of antisocial behavior in boys, and this was then replicated in the second sample. In particular, overt aggression (directly targeting another individual) was strongly associated with this genotype in boys (P=6.2 × 10(-7) in the discovery sample). Meta-analysis of the results for antisocial behavior from both samples yielded P=2.5 × 10(-5). Furthermore, an association between rs4564970 and LHA (P=0.00013) survived correction in the discovery sample, but there was no association with the SRD in the replication sample. We conclude that the rs7632287 and rs4564970 polymorphisms in OXTR may independently influence antisocial behavior in adolescent boys. Further replication of our results will be crucial to understanding how aberrant social behavior arises, and would support the OXT receptor as one potential target in the treatment of aggressive antisocial behavior.Molecular Psychiatry advance online publication, 22 September 2015; doi:10.1038/mp.2015.144.
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| 3. |
- Johansson, Daniel, et al.
(författare)
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Associations between oxytocin-related genes and autistic-like traits
- 2014
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Ingår i: Social Neuroscience. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 1747-0919 .- 1747-0927.
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Tidskriftsartikel (refereegranskat)abstract
- Oxytocin has repeatedly been shown to influence human behavior in social contexts; also, a relationship between oxytocin and the pathophysiology of autism spectrum disorder (ASD) has been suggested. In the present study, we investigated single-nucleotide polymorphisms (SNPs) in the oxytocin gene (OXT) and the genes for single-minded 1 (SIM1), aryl hydrocarbon receptor nuclear translocator 2 (ARNT2) and cluster of differentiation 38 (CD38) in a population of 1771 children from the Child and Adolescent Twin Study in Sweden (CATSS). Statistical analyses were performed to investigate any association between SNPs and autistic-like traits (ALTs), measured through ASD scores in the Autism-Tics, ADHD and other Co-morbidities inventory. Firstly, we found a statistically significant association between the SIM1 SNP rs3734354 (Pro352Thr) and scores for language impairment (p = .0004), but due to low statistical power this should be interpreted cautiously. Furthermore, nominal associations were found between ASD scores and SNPs in OXT, ARNT2 and CD38. In summary, the present study lends support to the hypothesis that oxytocin and oxytocin neuron development may have an influence on the development of ALTs and suggests a new candidate gene in the search for the pathophysiology of ASD.
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| 4. |
- Jonsson, Lina, 1982, et al.
(författare)
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Association between ASMT and autistic-like traits in children from a Swedish nationwide cohort
- 2014
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Ingår i: Psychiatric Genetics. - Stockholm : Lippincott Williams & Wilkins. - 0955-8829 .- 1473-5873. ; 24:1, s. 21-27
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Tidskriftsartikel (refereegranskat)abstract
- Individuals with autism spectrum disorders often show low levels of melatonin, and it has been suggested that this decrease may be because of the low activity of the acetylserotonin O-methyltransferase (ASMT), the last enzyme in the melatonin-synthesis pathway. Also, genetic variants in ASMT have been associated with autism, as well as with low ASMT activity and melatonin levels, suggesting that the low ASMT activity observed in autism may partly be because of variations within the ASMT gene. In this study, we present a symptom-based approach to investigate possible associations between ASMT and autistic-like traits in the general population. To this end, continuous measures of autistic-like traits were assessed in a nationally representative twin cohort (n=1771) from Sweden and six single nucleotide polymorphisms (SNPs), and a duplication of exons 2-8 in ASMT were genotyped. Our results show a nominally significant association, in girls, between one single nucleotide polymorphism (rs5949028) in the last intron of ASMT and social interaction impairments. No significant association, however, was observed with traits related to language impairment or restricted and repetitive behavior. In conclusion, our results support the possible involvement of the ASMT gene in autism spectrum disorders, and our finding that only one of the three traits shows association suggests that genetic research may benefit from adopting a symptom-specific approach to identify genes involved in autism psychopathology.
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| 5. |
- Jonsson, Lina, 1982, et al.
(författare)
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Association study between autistic-like traits and polymorphisms in the autism candidate regions RELN, CNTNAP2, SHANK3, and CDH9/10
- 2014
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Ingår i: Molecular Autism. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 2040-2392.
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Tidskriftsartikel (refereegranskat)abstract
- Background: Autistic-like traits (ALTs) are continuously distributed in the general population, with the autism spectrum disorder (ASD) at the upper extreme end. A genetic overlap has been shown between ALTs and ASD, indicating that common variation in ASD candidate genes may also influence ALTs. In our study, we have investigated the SNP rs4307059 that has been associated with both ALTs and ASD. In addition, we genotyped polymorphisms in a selection of genes involved in synaptic functioning, that is, SHANK3, RELN, and CNTNAP2, which repeatedly have been associated with ASD. The possible associations of these polymorphisms with ALTs, as well as genetic factors for neurodevelopmental problems (NDPs), were investigated in a large cohort from the general population: The Child and Adolescent Twin Study in Sweden. For analyses of ALTs and NDPs, 12,319 subjects (including 2,268 monozygotic (MZ) and 3,805 dizygotic (DZ) twin pairs) and 8,671 subjects (including 2,243 MZ and 2,044 DZ twin pairs), respectively, were included in the analyses. Findings: We could not replicate the previous association between rs4307059 and social communication impairment. Moreover, common variations in CNTNAP2 (rs7794745 and rs2710102), RELN (rs362691), and SHANK3 (rs9616915) were not significantly associated with ALTs in our study. Conclusions: Our results do not suggest that the investigated genes, which previously has been found associated with ASD diagnosis, have any major influence on ALTs in children from the general population.
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| 6. |
- Strenn, Nina, 1984, et al.
(författare)
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Associations between autistic-like traits and polymorphisms in NFKBIL1
- 2019
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Ingår i: Acta Neuropsychiatrica. - : Cambridge University Press (CUP). - 0924-2708 .- 1601-5215. ; 31:4, s. 220-229
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Tidskriftsartikel (refereegranskat)abstract
- Objective:The immune system has been suggested to be associated with neuropsychiatric disorders; for example, elevated levels of cytokines and the inflammation-related transcription factor nuclear factor kappa-B (NF-κB) have been reported in individuals with autism spectrum disorder (ASD). The aim of this study was to investigate possible associations between autistic-like traits (ALTs) and single nucleotide polymorphisms (SNPs) in NFKB1 (encoding a subunit of the NF-κB protein complex) and NF-κB inhibitor-like protein 1 (NFKBIL1).Methods:The study was conducted in a cohort from the general population: The Child and Adolescent Twin Study in Sweden (CATSS, n = 12 319, 9-12 years old). The subjects were assessed by the Autism-Tics, ADHD, and Other Comorbidities Inventory. Five SNPs within the two genes were genotyped (NFKBIL1: rs2857605, rs2239707, rs2230365 and rs2071592; NFKB1: rs4648022).Results:We found significant associations for two SNPs in NFKBIL1: rs2239707 showed a significant distribution of genotype frequencies in the case-control analysis both for all individuals combined and in boys only, and rs2230365 was significantly associated with the ALTs-module language impairment in boys only. Furthermore, we found nominal association in the case-control study for rs2230365, replicating earlier association between this SNP and ASD in an independent genome-wide association study.Conclusion:The shown associations between polymorphisms in NFKBIL1 and ALTs are supporting an influence of the immune system on neuropsychiatric symptoms. © Scandinavian College of Neuropsychopharmacology 2019.
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| 7. |
- Strenn, Nina, 1984, et al.
(författare)
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Associations between NFKB and NFKBIL1 polymorphisms and autistic-like traits in a Swedish population of twins
- 2014
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Ingår i: 29th World Congress of the International College of Neuropsychopharmacology (CINP), 22-26 June 2014; Vancouver, Canada.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Objectives Autism spectrum disorders are a complex group of neurodevelopmental disorders which are characterized by impairments in social interactions and both verbal and nonverbal communication. The immune system has been suggested to be of importance for the development of neuropsychiatric symptoms; for example, elevated levels of cytokines and the inflammation-related transcription factor nuclear factor kappa-B (NFKB) have been reported in autistic individuals. The aim of this study was to investigate possible associations between single nucleotide polymorphisms (SNPs) in NFKB and NFKB inhibitor-like protein 1 (NFKBIL1) and autistic-like traits in a Swedish population of twins. Methods The subjects in this study (n=12426, 9-12 years old) are from “The Child and Adolescent Twin Study in Sweden” (CATSS). Their parents participated in a telephone interview where the children were assessed by the Autism-Tics, ADHD, and Other Comorbidities Inventory (A-TAC) where autistic-like traits are measured using a continuous scale. DNA was extracted from saliva samples and polymorphisms were genotyped. Statistical analyses were performed in the SAS 9.3 (SAS Institute, Inc., Cary, NC) softwear. Results Four out of the five investigated SNPs (NFKB: rs4648022; NFKBIL1: rs2230365, 2239797 and rs2857605) showed significant associations with the A-TAC total autistic-like traits score. Conclusions To our best knowledge, polymorphisms in the genes encoding NFKB and NFKBIL1 have not been studied previously in relation to autism. These proteins may be involved in neuronal development and our findings support the hypothesis of the immune system being important in the aetiology of neuropsychiatric symptoms.
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| 8. |
- Zettergren, Anna, 1978, et al.
(författare)
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Associations between polymorphisms in sex steroid related genes and autistic-like traits.
- 2013
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Ingår i: Psychoneuroendocrinology. - : Elsevier BV. - 1873-3360 .- 0306-4530. ; 38:11
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Tidskriftsartikel (refereegranskat)abstract
- Sex differences in psychiatric disorders are common, which is particularly striking in autism spectrum disorders (ASDs) that are four times more prevalent in boys. High levels of testosterone during early development have been hypothesized to be a risk factor for ASDs, supported by several studies showing fetal testosterone levels, as well as indirect measures of prenatal androgenization, to be associated with ASDs and autistic-like traits (ALTs). Further, the importance of sex steroid related genes in ASDs is supported by studies reporting associations between polymorphisms in genes involved in sex steroid synthesis/metabolism and ASDs and ALTs. The aim of the present study was to investigate possible associations between 29 single nucleotide polymorphisms (SNPs) in eight genes related to sex steroids and autistic features. Individuals included in the study belong to a subset (n=1771) from The Child and Adolescent Twin Study in Sweden (CATSS), which are all assessed for ALTs. For two SNPs, rs2747648 located in the 3'-UTR of ESR1 encoding the estrogen receptor alpha and rs523349 (Leu89Val) located in SRD5A2 encoding 5-alpha-reductase, type 2, highly significant associations with ALTs were found in boys and girls, respectively. The results of the present study suggest that SNPs in sex steroid related genes, known to affect gene expression (rs2747648 in ESR1) and enzymatic activity (Leu89Val in SRD5A2), seem to be associated with ALTs in a general population. In conclusion, the current findings provide further support for a role of sex steroids in the pathophysiology of ASDs.
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| 9. |
- Zettergren, Anna, 1978, et al.
(författare)
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Further investigations of the relation between polymorphisms in sex steroid related genes and autistic-like traits.
- 2016
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Ingår i: Psychoneuroendocrinology. - Stockholm : Elsevier BV. - 1873-3360 .- 0306-4530. ; 68, s. 1-5
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Tidskriftsartikel (refereegranskat)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.
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