Polygenic risk scores for major depression, bipolar disorder, and schizophrenia were associated with first depression in the general population, according to data published in JAMA Psychiatry.

Investigators abstracted data from the iPSYCH2012 case-cohort sample, which comprises a representative sample of individuals in Denmark born between May 1, 1981, and December 31, 2005. The present analysis included all individuals from the iPSYCH2012 study who received a diagnosis of depression between 1991 and 2012 at 10 years of age or older. Individuals were genotyped using DNA from blood spots drawn from patients at birth and stored at the Danish Neonatal Screening Biobank. Individuals without Danish-born parents were excluded to reduce heterogeneity in genetic ancestry. Severity of psychiatric symptoms was also captured using International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10), code specifications and treatment setting. Cox regression analyses were performed to estimate the hazard for depression associated with certain polygenic liabilities.

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The final analysis included 34,573 participants aged 10 to 31 years at censoring, among whom 14,799 (43%) had major depression. The proportion of women among individuals with depression was 68% compared with just 49% among patients without depression. Age of onset for depression ranged from 10 to 31 years, with a mean (SD) of 19.1 (4.1) years. Depression cases were classified as mild (17%), moderate (45%), severe (9%), and severe with psychotic features (3%); 25% had no ICD-10 severity specification. The majority (60%) of cases were treated in an outpatient setting.

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Each standard deviation increase in polygenic liability for major depression, bipolar disorder, and schizophrenia was associated with 30% (hazard ratio [HR], 1.30; 95% confidence interval [CI], 1.27-1.33), 5% (HR, 1.05; 95% CI, 1.02-1.07), and 12% (HR, 1.12; 95% CI, 1.09-1.15) increases in the hazard for depression, respectively (all P <.0001). Compared with individuals in the bottom decile of polygenic risk scores, individuals in the top decile for major depression, bipolar disorder, and schizophrenia had hazard ratios of 2.55 (95% CI, 2.28-2.85), 1.22 (95% CI, 1.10-1.36), and 1.49 (95% CI, 1.34-1.66), respectively (all P <.0001). Among patients with depression, a higher polygenic liability for bipolar disorder was associated with earlier depression onset (P =.002). In addition, slight differences in depression severity were observed based on polygenic liability, with psychotic depression associated with higher hazard ratios.

Researchers concluded that polygenic risk for major depression was associated with first depression in the general population, suggesting an underlying genetic risk for the disorder in some. These data also suggest a common genetic overlap among bipolar disorder, schizophrenia, and depression.


Musliner KL, Mortensen PB, McGrath JJ, et al. Association of polygenic liabilities for major depression, bipolar disorder, and schizophrenia with risk for depression in the Danish population [published online January 30, 2019]. JAMA Psychiatry. doi: 10.1001/jamapsychiatry.2018.4166