title: Allelic variants in HTR3C show association with autism.
abstract: Autism spectrum disorders (ASDs) are severe neurodevelopmental disorders with a strong genetic component. Only a few predisposing genes have been identified so far. We have previously performed a genome-wide linkage screen for ASDs in Finnish families where the most significant linkage peak was identified at 3q25-27. Here, 11 positional and functionally relevant candidate genes at 3q25-27 were tested for association with autistic disorder. Genotypes of 125 single nucleotide polymorphisms (SNPs) were determined in 97 families with at least one individual affected with autistic disorder. The most significant association was observed using two non-synonymous SNPs in HTR3C, rs6766410 and rs6807362, both resulting in P = 0.0012 in family-based association analysis. In addition, the haplotype C-C corresponding to amino acids N163-A405 was overtransmitted to affected individuals (P = 0.006). Sequencing revealed no other variants in the coding region or splice sites of HTR3C. Based on the association analysis results in a previously identified linkage region, we propose that HTR3C represents a novel candidate locus for ASDs and should be tested in other populations.
authors.affiliation: Department of Molecular Medicine, National Public Health Institute and Institute for Molecular Medicine Finland, Helsinki, Finland. karola.rehnstrom@ktl.fi
authors.forename: Karola
authors.initials: K
authors.lastname: Rehnström
authors.forename: Tero
authors.initials: T
authors.lastname: Ylisaukko-oja
authors.forename: Ilona
authors.initials: I
authors.lastname: Nummela
authors.forename: Pekka
authors.initials: P
authors.lastname: Ellonen
authors.forename: Elli
authors.initials: E
authors.lastname: Kempas
authors.forename: Raija
authors.initials: R
authors.lastname: Vanhala
authors.forename: Lennart
authors.initials: L
authors.lastname: von Wendt
authors.forename: Irma
authors.initials: I
authors.lastname: Järvelä
authors.forename: Leena
authors.initials: L
authors.lastname: Peltonen
mesh_terms: D000483:Alleles; D001321:Autistic Disorder / Q000235:genetics*; D005190:Family; D005387:Finland; D005787:Gene Frequency; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D044406:Receptors, Serotonin, 5-HT3 / Q000235:genetics*
chemical_list: C543516:HTR3C protein, human; D044406:Receptors, Serotonin, 5-HT3