Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2010 Apr;122(1-2):14-26.
doi: 10.1016/j.jad.2009.06.014. Epub 2009 Oct 12.

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

K J Oedegaard  1 , T A Greenwood, A Lunde, O B Fasmer, H S Akiskal, J R Kelsoe; NIMH Genetics Initiative Bipolar Disorder Consortium
Affiliations

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

K J Oedegaard et al. J Affect Disord. 2010 Apr.

Abstract

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 genome-wide 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 co-morbidity 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 co-morbid 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 addition we 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 chromosome 4 (not co-segregating with BPAD) in a sample of BPAD families with co-morbid 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.

PubMed Disclaimer

Conflict of interest statement

Conflict of interest

None.

Figures

Fig. 1
Fig. 1
The linkage signal on chromosome 4 is a migraine signal. BP.narrow: BPAD I, schizoaffective, bipolar-type (SA-BP), BPAD II. Mig.broad: Migraine self-diagnosed. Mig.narrow: Migraine diagnosed by MD. BPmig.narrow: BPAD, schizoaffective, bipolar-type (SA-BP), BPAD II, RUDD + Migraine diagnose by MD.
Fig. 2
Fig. 2
The linkage signal on chromosome 20 is both a BPAD and migraine signal. BP.narrow: BPAD I, schizoaffective, bipolar-type (SA-BP), BPAD II. Mig. broad: Migraine self-diagnosed. Mig.narrow: Migraine diagnosed by MD. BPmig.narrow: BPAD, schizoaffective, bipolar-type (SA-BP), BPAD II, RUDD + Migraine diagnose by MD.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Abecasis GR, Cerny SS, Cookson WO, Cardon LR. Merlin: rapid analysis of dense genetic maps using sparse gene flow trees. Nat. Genet. 2002;30:97–101. - PubMed
    1. Akiskal HS, McKinney WT. Depressive disorders: toward a unified hypothesis. Science. 1973;182:20–29. - PubMed
    1. Anttila V, Kallela M, Oswell G, Kaunisto MA, Nyholt DR, Hamalainen E, Havanka H, Ilmavirta M, Terwilliger J, Sobel E, Peltonen L, Kaprio J, Farkkila M, Wessman M, Palotie A. Trait components provide tools to dissect the genetic susceptibility of migraine. Am. J. Hum. Genet. 2006;79(1):85–99. - PMC - PubMed
    1. Anttila V, Nyholt DR, Kallela M, Artto V, Vepsäläinen S, Jakkula E, Wennerström A, Tikka-Kleemola P, Kaunisto MA, Hämäläinen E, Widén E, Terwilliger J, Merikangas K, Montgomery GW, Martin NG, Daly M, Kaprio J, Peltonen L, Färkkilä M, Wessman M, Palotie A. Consistently replicating locus linked to migraine on 10q22–q23. Am. J. Hum. Genet. 2008;85(5):1051–1063. - PMC - PubMed
    1. Askland K, Parsons M. Toward a biaxial model of “bipolar” affective disorders: spectrum phenotypes as the products of neuroelectrical and neurochemical alterations. J. Affect. Disord. 2006;94:15–33. - PubMed

Publication types