Association study in siblings and case-controls of serotonin- and oxytocin-related genes with high functioning autism

BACKGROUND: 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. METHODS: In 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). RESULTS: We identified a nominal significant association with HFA for the HTTLPR s allele (consisting of S and L(G) 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). CONCLUSIONS: Our 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 MATERIAL: The online version of this article (doi:10.1186/2049-9256-2-1) contains supplementary material, which is available to authorized users.