Disruption of sonic hedgehog signaling in Ellis-van Creveld dwarfism confers protection against bipolar affective disorder

E. I. Ginns, M. Galdzicka, R. C. Elston, Y. E. Song, S. M. Paul, Janice Egeland

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Ellis-van Creveld syndrome, an autosomal recessively inherited chondrodysplastic dwarfism, is frequent among Old Order Amish of Pennsylvania. Decades of longitudinal research on bipolar affective disorder (BPAD) revealed cosegregation of high numbers of EvC and Bipolar I (BPI) cases in several large Amish families descending from the same pioneer. Despite the high prevalence of both disorders in these families, no EvC individual has ever been reported with BPI. The proximity of the EVC gene to our previously reported chromosome 4p16 BPAD locus with protective alleles, coupled with detailed clinical observations that EvC and BPI do not occur in the same individuals, led us to hypothesize that the genetic defect causing EvC in the Amish confers protection from BPI. This hypothesis is supported by a significant negative association of these two disorders when contrasted with absence of disease (P=0.029, Fisher's exact test, two-sided, verified by permutation to estimate the null distribution of the test statistic). As homozygous Amish EVC mutations causing EvC dwarfism do so by disrupting sonic hedgehog (Shh) signaling, our data implicate Shh signaling in the underlying pathophysiology of BPAD. Understanding how disrupted Shh signaling protects against BPI could uncover variants in the Shh pathway that cause or increase risk for this and related mood disorders.

Original languageEnglish (US)
Pages (from-to)1212-1218
Number of pages7
JournalMolecular Psychiatry
Volume20
Issue number10
DOIs
StatePublished - Oct 29 2015

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Amish
Dwarfism
Mood Disorders
Bipolar Disorder
Ellis-Van Creveld Syndrome
Chromosomes
Alleles
Mutation
Research
Genes

ASJC Scopus subject areas

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

Cite this

Disruption of sonic hedgehog signaling in Ellis-van Creveld dwarfism confers protection against bipolar affective disorder. / Ginns, E. I.; Galdzicka, M.; Elston, R. C.; Song, Y. E.; Paul, S. M.; Egeland, Janice.

In: Molecular Psychiatry, Vol. 20, No. 10, 29.10.2015, p. 1212-1218.

Research output: Contribution to journalArticle

Ginns, E. I. ; Galdzicka, M. ; Elston, R. C. ; Song, Y. E. ; Paul, S. M. ; Egeland, Janice. / Disruption of sonic hedgehog signaling in Ellis-van Creveld dwarfism confers protection against bipolar affective disorder. In: Molecular Psychiatry. 2015 ; Vol. 20, No. 10. pp. 1212-1218.
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