Department of Economics and Business Economics

Polygenic liability and depression in the iPSYCH2012 cohort

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Background: Although the usefulness of polygenic risk scores as a measure of genetic liability for major depressive disorder (MDD) has been established, their capacity to predict who will develop depression in the general population remains relatively unexplored. Our goals were to evaluate whether polygenic risk scores for MDD, bipolar disorder (BPD) and schizophrenia (SCZ) can predict depression in the general population, and explore whether these polygenic liabilities are associated with heterogeneity in age at onset and severity at initial depression diagnosis. Methods: Data were obtained from the iPSYCH2012 sample, a case-cohort sample comprised of a subcohort of 30,000 individuals randomly sampled from the Danish population and all additional individuals diagnosed in a psychiatric hospital with five different psychiatric disorders, including depression (ICD-10 codes F32, F33). For this study we included all genotyped individuals from the subcohort with Danish ancestry (N=20,158) along with all additional genotyped depression cases with Danish ancestry (N=18,030). Severity at depression diagnosis was assessed using the ICD-10 severity specifier (mild, moderate, severe without psychotic symptoms, severe with psychotic symptoms), and treatment setting (outpatient, inpatient, emergency). Age at onset (AAO) was operationalized as each individual's age in years at first depression diagnosis. Polygenic risk scores were trained using the most recent results from the PGC as discovery datasets. Hazard of depression was estimated using Cox regressions modified to accommodate the case-cohort design. Case-only analyses were conducted using linear and multinomial regressions. All models were adjusted for sex, birth year and the first 4 principal components. Results: In this nationally-representative sample of the Danish population, a one standard deviation increase in polygenic liability for MDD was associated with a 32% increase in hazard for depression (p < .0001). The corresponding increases associated with PRS-BPD and PRS-SCZ were 10% and 12%, respectively (p < .0001 for both). Hazard of depression was 2.65 times higher among individuals in the top decile of PRS-MDD relative to individuals in the bottom decile. PRS-MDD was not associated with differences in either AAO or severity, however among depression cases, PRS-BPD and PRS-SCZ showed small associations with earlier age at diagnosis (p = .013 for both), and PRS-BPD was associated with increased odds of inpatient (OR=1.05, 95% CI= [1.01-1.09]) and emergency (1.04, [1.00-1.08]) treatment. Discussion: Polygenic liability for MDD trained using prevalent samples of MDD cases predicts depression in the general population, suggesting that these scores are tapping in to an underlying liability for developing depression, not just risk for maintaining the disorder. The fact that PRS-BPD and PRS-SCZ also predict depression, although to a lesser extent than PRS-MDD, is consistent with prior results suggesting a degree of common genetic overlap among these disorders. Variation in polygenic loading for BPD and SCZ may contribute slightly to heterogeneity in clinical presentation at first diagnosis among depression cases.
Original languageEnglish
Publication year1 Jan 2019
Number of pages1
Publication statusPublished - 1 Jan 2019
EventWorld Congress of Psychiatric Genetics - Scottish Event Campus , Glasgow, United Kingdom
Duration: 11 Oct 201815 Oct 2018


ConferenceWorld Congress of Psychiatric Genetics
LocationScottish Event Campus
CountryUnited Kingdom

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