Abstract
Recently, markers in the Abelson Helper Integration Site 1 (AHI1) region were shown to be associated with schizophrenia in a family sample of Israeli-Arabs. Here, we report a study evaluating the relevance of the AHI1 region to schizophrenia in an Icelandic sample. Seven markers shown to confer risk in the previous report were typed in 608 patients diagnosed with broad schizophrenia and 1504 controls. Odds ratios for the overtransmitted alleles in the Israeli-Arab families ranged from 1.15 to 1.29 in the Icelandic sample. After Bonferroni correction for the seven markers tested, two markers were significantly associated with schizophrenia. Thus, our results are in general agreement with the previous report, with the strongest association signal observed in a region upstream of the AHI1 gene.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Sullivan PF, Kendler KS, Neale MC : Schizophrenia as a complex trait: evidence from a meta-analysis of twin studies. Arch Gen Psychiatry 2003; 60: 1187–1192.
Lewis CM, Levinson DF, Wise LH et al: Genome scan meta-analysis of schizophrenia and bipolar disorder, part II: Schizophrenia. Am J Hum Genet 2003; 73: 34–48.
Martinez M, Goldin LR, Cao Q et al: Follow-up study on a susceptibility locus for schizophrenia on chromosome 6q. Am J Med Genet 1999; 88: 337–343.
Levinson DF, Holmans P, Straub RE et al: Multicenter linkage study of schizophrenia candidate regions on chromosomes 5q, 6q, 10p, and 13q: schizophrenia linkage collaborative group III. Am J Hum Genet 2000; 67: 652–663.
Cao Q, Martinez M, Zhang J et al: Suggestive evidence for a schizophrenia susceptibility locus on chromosome 6q and a confirmation in an independent series of pedigrees. Genomics 1997; 43: 1–8.
Levi A, Kohn Y, Kanyas K et al: Fine mapping of a schizophrenia susceptibility locus at chromosome 6q23: increased evidence for linkage and reduced linkage interval. Eur J Hum Genet 2005; 13: 763–771.
Lerer B, Segman RH, Hamdan A et al: Genome scan of Arab Israeli families maps a schizophrenia susceptibility gene to chromosome 6q23 and supports a locus at chromosome 10q24. Mol Psychiatry 2003; 8: 488–498.
Amann-Zalcenstein D, Avidan N, Kanyas K et al: AHI1, a pivotal neurodevelopmental gene, and C6orf217 are associated with susceptibility to schizophrenia. Eur J Hum Genet 2006; 14: 1111–1119.
Ferland RJ, Eyaid W, Collura RV et al: Abnormal cerebellar development and axonal decussation due to mutations in AHI1 in Joubert syndrome. Nat Genet 2004; 36: 1008–1013.
Louie CM, Gleeson JG : Genetic basis of Joubert syndrome and related disorders of cerebellar development. Hum Mol Genet 2005; 14 Spec No 2: R235–R242.
Spitzer RL, Endicott J, Robins E : Research diagnostic criteria: rationale and reliability. Arch Gen Psychiatry 1978; 35: 773–782.
Endicott J, Spitzer RL : A diagnostic interview: the schedule for affective disorders and schizophrenia. Arch Gen Psychiatry 1978; 35: 837–844.
Amundadottir LT, Sulem P, Gudmundsson J et al: A common variant associated with prostate cancer in European and African populations. Nat Genet 2006; 38: 652–658.
Gretarsdottir S, Thorleifsson G, Reynisdottir ST et al: The gene encoding phosphodiesterase 4D confers risk of ischemic stroke. Nat Genet 2003; 35: 131–138.
Grant SF, Thorleifsson G, Reynisdottir I et al: Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes. Nat Genet 2006; 38: 320–323.
Sasaki T, Kotera J, Yuasa K, Omori K : Identification of human PDE7B, a cAMP-specific phosphodiesterase. Biochem Biophys Res Commun 2000; 271: 575–583.
Sasaki T, Kotera J, Omori K : Transcriptional activation of phosphodiesterase 7B1 by dopamine D1 receptor stimulation through the cyclic AMP/cyclic AMP-dependent protein kinase/cyclic AMP-response element binding protein pathway in primary striatal neurons. J Neurochem 2004; 89: 474–483.
Acknowledgements
We thank the patients participating in this study. Furthermore, we thank Hjördís Pálsdóttir, Hallbera Leifsdóttir, Ásta Snorradóttir and Þurí∂ur Þór∂ardóttir for assisting with the sample collection.
Author information
Authors and Affiliations
Corresponding author
Additional information
Electronic-Database Information
We obtained SNP genotypes for 30 Utah trios of Northern-European origin from the HapMap project database (http://www.hapmap.org/), and information on chromosomal coordinates and human gene annotation from the UCSC Genome Browser (http://genome.ucsc.edu/).
Supplementary Information accompanies the paper on European Journal of Human Genetics website (http://www.nature.com/ejhg)
Rights and permissions
About this article
Cite this article
Ingason, A., Sigmundsson, T., Steinberg, S. et al. Support for involvement of the AHI1 locus in schizophrenia. Eur J Hum Genet 15, 988–991 (2007). https://doi.org/10.1038/sj.ejhg.5201848
Received:
Revised:
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1038/sj.ejhg.5201848
Keywords
This article is cited by
-
Abelson Helper Integration Site 1 haplotypes and peripheral blood expression associates with lithium response and immunomodulation in bipolar patients
Psychopharmacology (2024)
-
Effect of chronic unpredictable stress on mice with developmental under-expression of the Ahi1 gene: behavioral manifestations and neurobiological correlates
Translational Psychiatry (2018)
-
Attempts to replicate genetic associations with schizophrenia in a cohort from north India
npj Schizophrenia (2017)
-
Neural mechanisms underlying stress resilience in Ahi1 knockout mice: relevance to neuropsychiatric disorders
Molecular Psychiatry (2014)
-
Cloning and Characterization of the Promoter of the Human AHI1 Gene
Biochemical Genetics (2009)
