“Bipolar Disorder and Its Relation to Major Psychiatric Disorders: a Family-Based Study in the Swedish Population”, Jie Song, Sarah E. Bergen, Ralf Kuja-Halkola, Henrik Larsson, Mikael Landén, Paul Lichtenstein2014-08-13 (genetic correlation, BP & autism, BP genes, depression, SCZ)⁠:

Objectives: Bipolar disorder (BPD) shares genetic components with other psychiatric disorders; however, uncertainty remains about where in the psychiatric spectra BPD falls. To understand the etiology of BPD, we studied the familial aggregation of BPD and co-aggregation between BPD and schizophrenia, depression, anxiety disorders, attention-deficit hyperactivity disorder, drug abuse, personality disorders, and autism spectrum disorders.

Method: A population-based cohort was created by linking several Swedish national registers. A total of 54,723 individuals with BPD were identified among 8,141,033 offspring from 4,149,748 nuclear families. The relative risk of BPD in relatives and the co-occurrence of other psychiatric disorders in patients with BPD and their relatives were compared to those of matched-population controls. Structural equation modeling was used to estimate the heritability and tetrachoric correlation.

Results: The familial risks for relatives of BPD probands were 5.8–7.9 in first-degree relatives, and decreased with genetic distance. Co-occurrence risks for other psychiatric disorders were 9.7–22.9 in individuals with BPD and 1.7–2.8 in full siblings of BPD probands. Heritability for BPD was estimated at 58%. The correlations between BPD and other psychiatric disorders were considerable (0.37–0.62) and primarily due to genetic effects. The correlation with depression was the highest (0.62), and was 0.44 for schizophrenia.

Conclusion: The high familial risks provide evidence that genetic factors play an important role in the etiology of BPD, and the shared genetic determinants suggest pleiotropic effects across different psychiatric disorders. Results also indicate that BPD is in both the mood and psychotic spectra, but possibly more closely related to mood disorders.

…Co-occurrence risk for psychiatric disorders among relatives of BPD probands: Our previous studies have shown the familial aggregation between BPD and schizophrenia⁴, BPD and ADHD¹⁶, and BPD and ASD¹⁷. This study extended investigations to depression, anxiety disorders, drug abuse, and personality disorders in the first/second/third-degree and adoptive relatives of BPD probands. Table 3 displays the results for different sibling types (results for all types of relationships are shown in Supplementary Table 2–8). Full siblings of BPD probands had statistically-significantly increased risks for all disorders investigated (RR = 1.7–2.8), and in sensitivity analyses (ie. excluding the possibility that individuals could be diagnosed with both disorders) these co-occurrences were somewhat attenuated but still statistically-significant (RR = 1.4–2.6; see Supplementary Table 9). Full siblings had higher risks for co-occurrence compared to half-siblings; maternal half-siblings had slightly higher risks than paternal half-siblings (except for schizophrenia). Adopted-away siblings whose biological sibling had BPD and grew up in a different family also had increased risks for depression, anxiety disorders, drug abuse, and personality disorders. Similar patterns of substantially increased risks appeared for all the disorders among first-degree relatives of BPD probands (see Supplementary Table 2–8). From these results, we noted high risks for ASD for adopted-away biological offspring of parents with BPD [RR = 5.5 (1.6–18.4)] and for adoptees of adoptive parents with BPD [RR = 2.2 (1.2–3.9)] (see Supplementary Table 8).