Abstract
AbstractPsychotic and affective disorders often aggregate in the relatives of probands with schizophrenia, and genetic studies show substantial genetic correlation among schizophrenia, bipolar disorder, and major depressive disorder. In this study, we examined the polygenic risk burden of bipolar disorder and major depressive disorder in 257 multiplex schizophrenia families (N = 1005) from the Irish Study of High-Density Multiplex Schizophrenia Families versus 2205 ancestry-matched controls. Our results indicate that members of multiplex schizophrenia families have an increased polygenic risk for bipolar disorder and major depressive disorder compared to population controls. However, this observation is largely attributable to the part of the genetic risk that bipolar disorder or major depressive disorder share with schizophrenia due to genetic correlation, rather than the affective portion of the genetic risk unique to them. These findings suggest that a complete interpretation of cross-disorder polygenic risks in multiplex families requires an assessment of the relative contribution of shared versus unique genetic factors to account for genetic correlations across psychiatric disorders.
Funder
U.S. Department of Health & Human Services | NIH | National Institute of Mental Health
Publisher
Springer Science and Business Media LLC
Reference49 articles.
1. Kendler, K. S. Diagnostic approaches to schizotypal personality disorder: a historical perspective. Schizophr. Bull. 11, 538–553 (1985).
2. Kety, S. S., Rosenthal, D., Wender, P. H., Schulsinger, F. & Jacobsen, B. Mental illness in the biological and adoptive families of adopted individuals who have become schizophrenic: a preliminary report based on psychiatric interviews. Proc. Annu. Meet. Am. Psychopathol. Assoc. 63, 147–165 (1975).
3. Wray, N. R. et al. Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression. Nat. Genet. 50, 668–681 (2018).
4. Mullins, N. et al. Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology. Nat. Genet. 53, 817–829 (2021).
5. Trubetskoy, V. et al. Mapping genomic loci implicates genes and synaptic biology in schizophrenia. Nature 604, 502–508 (2022).
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