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A genome-wide linkage study of bipolar disorder and co-morbid migraine: Replication of migraine linkage on chromosome 4q24, and suggestion of an overlapping susceptibility region for both disorders on chromosome 20p11

Publication: Research - peer-reviewJournal article

  • K. J. Oedegaard
    K. J. OedegaardDepartment of Psychiatry, University of California San DiegoUnited States
  • T. A. Greenwood
    T. A. GreenwoodDepartment of Psychiatry, University of California San DiegoUnited States
  • Asger Lunde
  • O. B. Fasmer
    O. B. FasmerDepartment of Clinical Medicine, University of BergenNorway
  • H. S. Akiskal
    H. S. AkiskalDepartment of Psychiatry, University of California San DiegoUnited States
  • J. R. Kelsoe
    J. R. KelsoeDepartment of Psychiatry, University of California San DiegoUnited States
Migraine and Bipolar Disorder (BPAD) are clinically heterogeneous disorders of the brain with a significant, but complex, genetic component. Epidemiological and clinical studies have demonstrated a high degree of co-morbidity between migraine and BPAD. Several genomewide linkage studies in BPAD and migraine have shown overlapping regions of linkage on chromosomes, and two functionally similar voltage-dependent calcium channels CACNA1A and CACNA1C have been identified in familial hemiplegic migraine and recently implicated in two whole genome BPAD association studies, respectively.We hypothesized that using migraine comorbidity to look at subsets of BPAD families in a genetic linkage analysis would prove useful in identifying genetic susceptibility regions in both of these disorders. We used BPAD with comorbid migraine as an alternative phenotype definition in a re-analysis of the NIMH Bipolar Genetics Initiative wave 4 data set. In this analysis we selected only those families in which at least two members were diagnosed with migraine by a doctor according to patients' reports. Nonparametric linkage analysis performed on 31 families segregating both BPAD and migraine identified a linkage signal on chromosome 4q24 for migraine (but not BPAD) with a peak LOD of 2.26. This region has previously been implicated in two independent migraine linkage studies. In additionwe identified a locus on chromosome 20p11 with overlapping elevated LOD scores for both migraine (LOD=1.95) and BPAD (LOD=1.67) phenotypes. This region has previously been implicated in two BPAD linkage studies, and, interestingly, it harbors a known potassium dependant sodium/calcium exchanger gene, SLC24A3, that plays a critical role in neuronal calcium homeostasis. Our findings replicate a previously identified migraine linkage locus on chrom osome 4 (not co-segregating with BPAD) in a sample of BPAD families with comorbid migraine, and suggest a susceptibility locus on chromosome 20, harboring a gene for the migraine/BPAD phenotype. Together these data suggest that some genes may predispose to both bipolar disorder and migraine.
Original languageEnglish
JournalJournal of Affective Disorders
Volume122
Issue number1-2
Pages (from-to)14-26
Number of pages13
ISSN0165-0327
DOIs
StatePublished - 2010

    Keywords

  • Migraine, Bipolar disorder, Linkage, Chromosome 4q24, Chromosome 20p11

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