Polymorphisms in the GRIA1 gene region in psychotic bipolar disorder

Authors

  • Berit Kerner,

    Corresponding author
    1. Center for Neurobehavioral Genetics, Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California at Los Angeles, Los Angeles, California
    • Center for Neurobehavioral Genetics, Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, 695 Charles E Young Drive South, Room 3554A, Box 951761, Los Angeles, CA 90095-1761.
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  • Anna J. Jasinska,

    1. Center for Neurobehavioral Genetics, Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California at Los Angeles, Los Angeles, California
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  • Joseph DeYoung,

    1. Center for Neurobehavioral Genetics, Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California at Los Angeles, Los Angeles, California
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  • Maricel Almonte,

    1. Center for Neurobehavioral Genetics, Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California at Los Angeles, Los Angeles, California
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  • Oi-Wa Choi,

    1. Center for Neurobehavioral Genetics, Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California at Los Angeles, Los Angeles, California
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  • Nelson B. Freimer

    1. Center for Neurobehavioral Genetics, Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California at Los Angeles, Los Angeles, California
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  • Please cite this article as follows: Kerner B, Jasinska AJ, DeYoung J, Almonte M, Choi O-W, Freimer NB. 2008. Polymorphisms in the GRIA1 gene region in psychotic bipolar disorder. Am J Med Genet Part B 150B:24–32.

Abstract

We reported previously a significant linkage signal between psychotic bipolar disorder (BP) and microsatellite markers on chromosome 5q31–34 in the National Institute of Mental Health Bipolar Genetics Initiative (NIMH-BPGI) data set, Wave 1. In an attempt to fine-map this linkage signal we genotyped 1,134 single nucleotide polymorphisms (SNPs) under the linkage peak in 23 informative families (131 individuals) with evidence of linkage. We tested family based association in the presence of linkage with the computer software package FBAT. The most significant association in these families was with a SNP in the second intron of GRIA1 (α-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid (AMPA) subunit 1 receptor gene) (rs490922, Z-score = 3.3, P = 0.001). The analysis of 37 additional families with psychotic BP from NIMH-BPGI data sets, Waves 2, 3, and 4 revealed a signal at a SNP in intron 5 of the GRIA1 gene (rs4385264, Z-score = 3.2, P-value = 0.002). A combined analysis of all 60 families continued to support evidence for association of GRIA1 with psychotic BP; however, individual SNPs could not be replicated across datasets. The AMPA1 receptor has been shown to influence cognitive function, such as working memory and reward learning. Our findings suggest that variations in this receptor may contribute to the pathophysiology of BP with psychotic features in some families. © 2008 Wiley-Liss, Inc.

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