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CNTNAP2 gene in high functioning autism: no association according to family and meta-analysis approaches

  • Psychiatry and Preclinical Psychiatric Studies - Original Article
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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.

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Abbreviations

ADHD:

Attention deficit/hyperactivity disorder

ADI-R:

Autism diagnosis interview-revised

ADOS:

Autism diagnosis observation schedule

ASD:

Autism spectrum disorder

BP:

Base pair

CASPR2:

Contactin-associated protein-2

CDFE:

Cortical dysplasia-focal epilepsy

CFT:

Culture fair test

CNTN6:

Contactin 6

CNTNAP2:

Contactin associated protein-like 2

ICD-10:

International statistical classification of diseases and related health problems, 10th Revision

DNA:

Deoxyribonucleic acid

ID:

Intellectual disability

HFA:

High functioning autism

FOXP2:

Forkhead box protein P2

DFAM:

Family-based association for disease traits

IQ:

Intelligence quotient

SON-R:

Snijders-oomen non-verbal intelligence test

SNP:

Single nucleotide polymorphism

TDT:

Transmission disequilibrium test

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Acknowledgments

We thank all participants who took part in this study for their important contribution and willingness. We thank Miryame Hofmann for her technical assistance. The study was partially supported by the “Studienstiftung Deutschland” for EB and the “Bundesprogramm Chancengleichheit” 2009–2011 of the University Zurich.

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    Authors and Affiliations

    1. University Clinic of Child and Adolescent Psychiatry, University of Zurich, Zurich, Switzerland

      Anna Maria Werling, Ronnie Gundelfinger, Edna Grünblatt & Susanne Walitza

    2. Department of Experimental Psychology, University of Regensburg, Regensburg, Germany

      Elise Bobrowski

    3. Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University of Wuerzburg, Wuerzburg, Germany

      Regina Taurines & Marcel Romanos

    4. Neuroscience Center Zurich, University of Zurich and ETH Zurich, Zurich, Switzerland

      Edna Grünblatt & Susanne Walitza

    5. Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Zurich, Switzerland

      Susanne Walitza

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    Correspondence to Edna Grünblatt or Susanne Walitza.

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    E. Grünblatt and S. Walitza contributed equally.

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    Werling, A.M., Bobrowski, E., Taurines, R. et al. CNTNAP2 gene in high functioning autism: no association according to family and meta-analysis approaches. J Neural Transm 123, 353–363 (2016). https://doi.org/10.1007/s00702-015-1458-5

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    • DOI: https://doi.org/10.1007/s00702-015-1458-5

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