Shared genetic risk between schizophrenia (SCZ) and bipolar disorder (BD) is well-established, yet the extent to which they share environmental risk factors remains unclear. We compare the associations between environmental exposures during childhood/prior to disorder onset with the risk of developing SCZ and BD.

We conducted a Swedish register-based nested case–control study using 4184 SCZ cases and 18 681 BD cases diagnosed 1988–2013. Cases were matched to five controls by birth year, birth region, and sex. Conditional logistic regression was used to estimate incidence rate ratios (IRR) for SCZ and BD for each exposure (severe childhood infections, adverse childhood experiences (ACEs), substance use disorders (SUDs), urban birth/longest residence).

All SUD types were associated with very high risk (IRR 4.9–25.5), and all forms of ACEs with higher risk (IRR 1.5–4.3) for both disorders. In the mutually adjusted models, ACEs demonstrated slightly higher risk for BD (SCZ IRR 1.30, 1.19-1.42; BD IRR 1.49, 1.44–1.55), while for SUD, risk was higher for SCZ (SCZ IRR 9.43, 8.15–10.92; BD IRR 5.50, 5.15–5.88). Infections were associated with increased risk of BD (IRR 1.21, 1.17–1.26) but not SCZ. Urban birth and urban longest residence were associated with higher risk of SCZ (IRR 1.19, 1.03–1.37), while only the combination of urban birth and rural longest residence showed higher risk for BD (IRR 1.24, 1.13–1.35).

There were both shared and unique environmental risk factors: SUDs and ACEs were risk factors for both disorders, while infections were more strongly associated with BD and urbanicity with SCZ.

Familial co-aggregation studies of eating disorders (EDs) and schizophrenia reveal shared genetic and environment factors, yet their etiological and clinical relationship remains unclear. We evaluate the influence of schizophrenia family history on clinical outcomes of EDs.

We conducted a cohort evaluation of the association between family history of schizophrenia and ED clinical features, psychiatric comorbidities, and somatic and mental health burden in individuals born in Sweden 1977–2003 with anorexia nervosa (AN) or other EDs (OED: bulimia nervosa, binge-eating disorder, and ED not otherwise specified).

Of 12 424 individuals with AN and 20 716 individuals with OED, 599 (4.8%) and 1118 (5.4%), respectively, had a family history of schizophrenia (in up to third-degree relatives). Among individuals with AN, schizophrenia in first-degree relatives was significantly associated with increased comorbid attention-deficit/hyperactivity disorder (ADHD) [HR(95% CI) 2.26 (1.27–3.99)], substance abuse disorder (SUD) [HR (95% CI) 1.93 (1.25–2.98)], and anxiety disorders [HR (95% CI) 1.47 (1.08–2.01)], but higher lowest illness-associated body mass index (BMI) [1.14 kg/m2, 95% CI (0.19–2.10)]. Schizophrenia in any relative (up to third-degree) in AN was significantly associated with higher somatic and mental health burden, but lower ED psychopathology scores [−0.29, 95% CI (−0.54 to −0.04)]. Schizophrenia in first-degree relatives in individuals with OED was significantly associated with increased comorbid ADHD, obsessive-compulsive disorder, SUD, anxiety disorders, somatic and mental health burden, and suicide attempts.

We observed different patterns of ED-related outcomes, psychiatric comorbidity, and illness burden in individuals with EDs with and without family histories of schizophrenia and provide new insights into the diverse manifestations of EDs.

Bipolar disorder is a highly heritable polygenic disorder. Recent enrichment analyses suggest that there may be true risk variants for bipolar disorder in the expression quantitative trait loci (eQTL) in the brain.

We sought to assess the impact of eQTL variants on bipolar disorder risk by combining data from both bipolar disorder genome-wide association studies (GWAS) and brain eQTL.

To detect single nucleotide polymorphisms (SNPs) that influence expression levels of genes associated with bipolar disorder, we jointly analysed data from a bipolar disorder GWAS (7481 cases and 9250 controls) and a genome-wide brain (cortical) eQTL (193 healthy controls) using a Bayesian statistical method, with independent follow-up replications. The identified risk SNP was then further tested for association with hippocampal volume (n = 5775) and cognitive performance (n = 342) among healthy individuals.

Integrative analysis revealed a significant association between a brain eQTL rs6088662 on chromosome 20q11.22 and bipolar disorder (log Bayes factor = 5.48; bipolar disorder P = 5.85×10–5). Follow-up studies across multiple independent samples confirmed the association of the risk SNP (rs6088662) with gene expression and bipolar disorder susceptibility (P = 3.54×10–8). Further exploratory analysis revealed that rs6088662 is also associated with hippocampal volume and cognitive performance in healthy individuals.

Our findings suggest that 20q11.22 is likely a risk region for bipolar disorder; they also highlight the informative value of integrating functional annotation of genetic variants for gene expression in advancing our understanding of the biological basis underlying complex disorders, such as bipolar disorder.