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β2-Adrenergic receptor gene variants and risk for autism in the AGRE cohort

Molecular Psychiatry volume 12, pages 283–291 (2007)Cite this article

Abstract

The β2-adrenergic receptor is part of the catecholamine system, and variants at two polymorphic sites in the gene coding for the receptor (ADRB2) confer increased activity. Overstimulation of this receptor may alter brain development, and has been linked to autism in non-identical twins. The objective of this study was to determine whether alleles in ADRB2 are associated with diagnosis of autism in the Autism Genetic Resource Exchange (AGRE) population. Three hundred and thirty-one independent autism case–parent trios were included in the analysis. Subjects were genotyped at activity-related polymorphisms rs1042713 (codon 16) and rs1042714 (codon 27). Association between autism and genotypes at each polymorphic site was tested using genotype-based transmission disequilibrium tests, and effect modification by family and pregnancy characteristics was evaluated. Sensitivity to designation of the proband in each family was assessed by performing 1000 repeats of the analysis selecting affected children randomly. A statistically significant OR of 1.66 for the Glu27 homozygous genotype was observed. Increased associations with this genotype were observed among a subset of Autism Diagnostic Observation Schedule confirmed cases and a subset reporting experience of pregnancy-related stressors. In conclusion, the Glu27 allele of the ADRB2 gene may confer increased risk of autism and shows increased strength with exposure to pregnancy related stress.

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Acknowledgements

We gratefully acknowledge the resources provided by the Autism Genetic Resource Exchange (AGRE) Consortium* and the participating AGRE families. The AGRE is a program of Cure Autism Now and is supported, in part, by Grant MH64547 from the National Institute of Mental Health to Daniel H Geschwind (PI). This research was also supported by cooperative agreement U10CCU320408 from the National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention and a National Alliance for Autism Research (NAAR) Pre-Doctoral Fellowship. *The AGRE Consortium: Dan Geschwind, MD, PhD, UCLA, Los Angeles, CA, USA; Maja Bucan, PhD, University of Pennsylvania, Philadelphia, PA, USA; W Ted Brown, MD, PhD, FACMG, NYS, Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA; Rita M Cantor, PhD, UCLA School of Medicine, Los Angeles, CA, USA; John N Constantino, MD, Washington University School of Medicine, St Louis, MO, USA; T Conrad Gilliam, PhD, University of Chicago, Chicago, IL, USA; Martha Herbert, MD, PhD, Harvard Medical School, Boston, MA, USA; Clara Lajonchere, PhD, Cure Autism Now, Los Angeles, CA, USA; David H Ledbetter, PhD, Emory University, Atlanta, GA, USA; Christa Lese-Martin, PhD, Emory University, Atlanta, GA, USA; Janet Miller, JD, PhD, Cure Autism Now, Los Angeles, CA, USA; Stanley F Nelson, MD, UCLA School of Medicine, Los Angeles, CA, USA; Gerard D Schellenberg, PhD, University of Washington, Seattle, WA, USA; Carol A Samango-Sprouse, EdD, George Washington University, Washington, DC, USA; Sarah Spence, MD, PhD, UCLA, Los Angeles, CA, USA; Matthew State, MD, PhD, Yale University, New Haven, CT, USA; Rudolph E Tanzi, PhD, Massachusetts General Hospital, Boston, MA, USA.

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Authors and Affiliations

  1. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA

    K Cheslack-Postava, M D Fallin & C J Newschaffer

  2. Department of Psychiatry and Institute of Genetic Medicine, Johns Hopkins University, Baltimore, MD, USA

    D Avramopoulos

  3. Department of Neurology and Developmental Medicine, Kennedy Krieger Institute, Baltimore, MD, USA

    S L Connors & A W Zimmerman

  4. Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    C G Eberhart

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  1. K Cheslack-Postava
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Correspondence to C J Newschaffer.

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Cheslack-Postava, K., Fallin, M., Avramopoulos, D. et al. β2-Adrenergic receptor gene variants and risk for autism in the AGRE cohort. Mol Psychiatry 12, 283–291 (2007). https://doi.org/10.1038/sj.mp.4001940

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