title: CNTNAP2 gene in high functioning autism: no association according to family and meta-analysis approaches.
abstract: The Contactin Associated Protein-like 2 (CNTNAP2) gene has been discussed to be associated with different symptoms of autism spectrum disorders (ASDs) and other neurodevelopmental disorders. We aimed to elucidate the genetic association of CNTNAP2 within high functioning ASD (HFA), focusing on autism specific symptoms and reducing intelligence related factors. Furthermore, we compared our findings conducting a meta-analysis in patients with ASD and HFA only. A case-control association study was performed for HFA (HFA, n = 105; controls, n = 133). Moreover, we performed a family-based association study (DFAM) analysis (HFA, n = 44; siblings, n = 57). Individuals were genotyped for the two most frequently reported single nucleotide polymorphisms (SNPs) in the CNTNAP2 gene (rs2710102, rs7794745). Furthermore, a meta-analysis using the MIX2 software integrated our results with previously published data. A significant association for the carriers of the T-allele of the rs7794745 with HFA was found in the case-control sample [OR = 1.547; (95 % CI 1.056-2.266); p = 0.025]. No association could be found by DFAM with any of the CNTNAP2 SNPs with HFA. The meta-analysis of both SNPs did not show a significant association with either ASD or with HFA. Overall, including case-control, sibs, and meta-analysis, we could not detect any significant association with the CNTNAP2 gene and HFA. Our results point in the direction that CNTNAP2 may not play a major role in HFA, but rather seems to have a significance in neurodevelopmental disorders or in individuals displaying intellectual delays.
authors.affiliation: University Clinic of Child and Adolescent Psychiatry, University of Zurich, Zurich, Switzerland. anna.werling@kjpdzh.ch.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Werling
authors.affiliation: Department of Experimental Psychology, University of Regensburg, Regensburg, Germany. elise@bobrowski.org.
authors.forename: Elise
authors.initials: E
authors.lastname: Bobrowski
authors.affiliation: Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University of Wuerzburg, Wuerzburg, Germany. Taurines_R@ukw.de.
authors.forename: Regina
authors.initials: R
authors.lastname: Taurines
authors.affiliation: University Clinic of Child and Adolescent Psychiatry, University of Zurich, Zurich, Switzerland. ronnie.gundelfinger@kjpdzh.ch.
authors.forename: Ronnie
authors.initials: R
authors.lastname: Gundelfinger
authors.affiliation: Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University of Wuerzburg, Wuerzburg, Germany. Romanos_M@ukw.de.
authors.forename: Marcel
authors.initials: M
authors.lastname: Romanos
authors.affiliation: University Clinic of Child and Adolescent Psychiatry, University of Zurich, Zurich, Switzerland. edna.gruenblatt@kjpdzh.ch.|Neuroscience Center Zurich, University of Zurich and ETH Zurich, Zurich, Switzerland. edna.gruenblatt@kjpdzh.ch.
authors.forename: Edna
authors.initials: E
authors.lastname: Grünblatt
authors.affiliation: University Clinic of Child and Adolescent Psychiatry, University of Zurich, Zurich, Switzerland. susanne.walitza@kjpdzh.ch.|Neuroscience Center Zurich, University of Zurich and ETH Zurich, Zurich, Switzerland. susanne.walitza@kjpdzh.ch.|Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Zurich, Switzerland. susanne.walitza@kjpdzh.ch.
authors.forename: Susanne
authors.initials: S
authors.lastname: Walitza
mesh_terms: D000293:Adolescent; D001321:Autistic Disorder / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D035781:Siblings
chemical_list: C403049:CNTNAP2 protein, human; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins
keywords: CNTNAP2; High functioning autism; Meta-analysis; Polymorphism