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.
Highlights
Bipolar disorder (BP) affects about 1% of the population, causing significant disability worldwide
Post-hoc tests showed that there was a significant difference between the Quantitative Bipolarity Scale (QBS) score in subjects with BP (31.5 ± 3.6, mean ± s.e.) compared to major depressive disorder (MDD) (16.7 ± 2.0), other psychiatric diagnosis (7.0 ± 1.9), and no psychiatric diagnosis (6.0 ± 0.65)
We investigated whether bipolarity quantification can capture the genetic risk for BP beyond that obtained by categorical diagnoses
Summary
Bipolar disorder (BP) affects about 1% of the population, causing significant disability worldwide. Case-control genome-wide association studies (GWAS) are beginning to illuminate the genetic risk for this complex polygenic disorder and have identified a number of loci[4,5,6] though findings have been difficult to replicate. Most genetic studies of BP define the study group by diagnosis. While this definition is important for clinical care of BP patients, whether this is the correct phenotype to use to search for genes conferring risks for BP is not clear. Susceptible individuals without BP expression may be missed or even erroneously grouped into the control groups. Our hypothesis is that bipolarity is expressed in BP but may be a heritable subclinical trait that is present even in non-bipolar individuals, yet much more severe in BP and as such separates BP from other psychiatric diagnoses
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
