Abstract
BackgroundAutism spectrum disorder (ASD) is heritable and neurodevelopmental with unknown causes. The serotonergic and oxytocinergic systems are of interest in autism for several reasons: (i) Both systems are implicated in social behavior, and abnormal levels of serotonin and oxytocin have been found in people with ASD; (ii) treatment with selective serotonin reuptake inhibitors and oxytocin can yield improvements; and (iii) previous association studies have linked the serotonin transporter (SERT; SLC6A4), serotonin receptor 2A (HTR2A), and oxytocin receptor (OXTR) genes with ASD. We examined their association with high functioning autism (HFA) including siblings and their interaction.MethodsIn this association study with HFA children (IQ > 80), siblings, and controls, participants were genotyped for four single nucleotide polymorphisms (SNPs) in OXTR (rs2301261, rs53576, rs2254298, rs2268494) and one in HTR2A (rs6311) as well as the triallelic HTTLPR (SERT polymorphism).ResultsWe identified a nominal significant association with HFA for the HTTLPR s allele (consisting of S and LG alleles) (p = .040; odds ratio (OR) = 1.697, 95% CI 1.191–2.204)). Four polymorphisms (HTTLPR, HTR2A rs6311, OXTR rs2254298 and rs53576) in combination conferred nominal significant risk for HFA with a genetic score of ≥4 (OR = 2.09, 95% CI 1.05–4.18, p = .037). The resulting area under the receiver operating characteristic curve was 0.595 (p = .033).ConclusionsOur findings, combined with those of previous reports, indicate that ASD, in particular HFA, is polygenetic rather than monogenetic and involves the serotonergic and oxytocin pathways, probably in combination with other factors.Electronic supplementary materialThe online version of this article (doi:10.1186/2049-9256-2-1) contains supplementary material, which is available to authorized users.
Highlights
Autism spectrum disorder (ASD) is heritable and neurodevelopmental with unknown causes
(HTR2A) and serotonin transporter (SERT, known as 5-HTT) binding in certain brain regions of people with ASD has been identified [17,18,19]; (iv) selective serotonin reuptake inhibitors (SSRIs) can improve abnormal reciprocal social interaction and repetitive behaviors in some cases [20,21,22,23]; and (v) several polymorphisms in the HTR2A gene (NCBI Gene ID: 3356) and the SERT gene have suggested association with ASD [24,25,26,27,28,29]. We focus on these two candidate genes: The promoter sequence of SERT contains a polymorphic region (HTTLPR) with a short allele (S) and a long allele (L) that is 44 bp longer and can contain an additional single nucleotide polymorphism (SNP), making the locus triallelic (LA, LG and S) [30,31]
Association of single SNPs with autism diagnosis To investigate whether oxytocinergic and serotonergic system genes are associated with high functioning autism (HFA), 253 children were genotyped for polymorphisms in the oxytocin receptor (OXTR), HTR2A, and SERT
Summary
Autism spectrum disorder (ASD) is heritable and neurodevelopmental with unknown causes. The serotonergic and oxytocinergic systems are of interest in autism for several reasons: (i) Both systems are implicated in social behavior, and abnormal levels of serotonin and oxytocin have been found in people with ASD; (ii) treatment with selective serotonin reuptake inhibitors and oxytocin can yield improvements; and (iii) previous association studies have linked the serotonin transporter (SERT; SLC6A4), serotonin receptor 2A (HTR2A), and oxytocin receptor (OXTR) genes with ASD. We examined their association with high functioning autism (HFA) including siblings and their interaction. Association studies of HTR2A have concentrated mostly on three non-coding SNPs (rs6311, rs6313, rs6314) [26,27,28,32]
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