The genetics of early-onset bipolar disorder: A systematic review

- Genetic variant has not been convincingly associated with early-onset BD.
- No robust evidence of qualitative genetic differences between early- and late-onset BD.
- Little evidence that early-onset “subtype” improves genetic homogeneity for GWAS.
- Standardized atheoretical methods and larger sample sizes needed in future research.

BackgroundEarly-onset bipolar disorder has been associated with a significantly worse prognosis than late-onset BD and has been hypothesized to be a genetically homogenous subset of BD. A sizeable number of studies have investigated early-onset BD through linkage-analyses, candidate-gene association studies, genome-wide association studies (GWAS), and analyses of copy number variants (CNVs), but this literature has not yet been reviewed.MethodsA systematic review was conducted using the PubMed database on articles published online before January 15, 2015 and after 1990. Separate searches were made for linkage studies, candidate gene-association studies, GWAS, and studies on CNVs.ResultsSeventy-three studies were included in our review. There is a lack of robust positive findings on the genetics of early-onset BD in any major molecular genetics method.LimitationsEarly-onset populations were quite small in some studies. Variance in study methods hindered efforts to interpret results or conduct meta-analysis.ConclusionsThe field is still at an early phase for research on early-onset BD. The largely null findings mirror the results of most genetics research on BD. Although most studies were underpowered, the null findings could mean that early-onset BD may not be as genetically homogenous as has been hypothesized or even that early-onset BD does not differ genetically from adult-onset BD. Nevertheless, clinically the probabilistic developmental risk trajectories associated with early-onset that may not be primarily genetically determined continued to warrant scrutiny. Future research should dramatically expand sample sizes, use atheoretical research methods like GWAS, and standardize methods.