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    Clinical and genetic validity of quantitative bipolarity

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    Author
    Bruce, H.A.
    Kochunov, P.
    Mitchell, B.
    Strauss, K.A.
    Ament, S.A.
    Rowland, L.M.
    Du, X.
    Fisseha, F.
    Kavita, T.
    Chiappelli, J.
    Wisner, K.
    Sampath, H.
    Chen, S.
    Kvarta, M.D.
    Postolache, T.T.
    Shuldiner, A.
    Elliot, Hong, L.
    Seneviratne, C.
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    Date
    2019
    Journal
    Translational psychiatry
    Publisher
    Nature Publishing Group
    Type
    Article
    
    Metadata
    Show full item record
    See at
    https://doi.org/10.1038/s41398-019-0561-z
    Abstract
    Research has yet to provide a comprehensive understanding of the genetic basis of bipolar disorder (BP). In genetic studies, defining the phenotype by diagnosis may miss risk-allele carriers without BP. The authors aimed to test whether quantitatively detected subclinical symptoms of bipolarity identifies a heritable trait that infers risk for BP. The Quantitative Bipolarity Scale (QBS) was administered to 310 Old Order Amish or Mennonite individuals from multigenerational pedigrees; 110 individuals had psychiatric diagnoses (20 BP, 61 major depressive disorders (MDD), 3 psychotic disorders, 26 other psychiatric disorders). Familial aggregation of QBS was calculated using the variance components method to derive heritability and shared household effects. The QBS score was significantly higher in BP subjects (31.5 ± 3.6) compared to MDD (16.7 ± 2.0), other psychiatric diagnoses (7.0 ± 1.9), and no psychiatric diagnosis (6.0 ± 0.65) (all p < 0.001). QBS in the whole sample was significantly heritable (h2 = 0.46 ± 0.15, p < 0.001) while the variance attributed to the shared household effect was not significant (p = 0.073). When subjects with psychiatric illness were removed, the QBS heritability was similar (h2 = 0.59 ± 0.18, p < 0.001). These findings suggest that quantitative bipolarity as measured by QBS can separate BP from other psychiatric illnesses yet is significantly heritable with and without BP included in the pedigrees suggesting that the quantitative bipolarity describes a continuous heritable trait that is not driven by a discrete psychiatric diagnosis. Bipolarity trait assessment may be used to supplement the diagnosis of BP in future genetic studies and could be especially useful for capturing subclinical genetic contributions to a BP phenotype.
    Keyword
    Quantitative Bipolarity Scale
    Bipolar Disorder--diagnosis
    Bipolar Disorder--genetics
    Identifier to cite or link to this item
    https://www.scopus.com/inward/record.uri?eid=2-s2.0-85072300292&doi=10.1038%2fs41398-019-0561-z&partnerID=40&md5=493121f0ee73482d341692a0b105eeca; http://hdl.handle.net/10713/11024
    ae974a485f413a2113503eed53cd6c53
    10.1038/s41398-019-0561-z
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