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  • Musliner, Katherine L., et al. (författare)
  • Association of Polygenic Liabilities for Major Depression, Bipolar Disorder, and Schizophrenia With Risk for Depression in the Danish Population
  • 2019
  • Ingår i: JAMA psychiatry. - Chicago : American Medical Association. - 2168-6238. ; 76:5, s. 516-525
  • Tidskriftsartikel (refereegranskat)abstract
    • IMPORTANCE: Although the usefulness of polygenic risk scores as a measure of genetic liability for major depression (MD) has been established, their association with depression in the general population remains relatively unexplored.OBJECTIVE: To evaluate whether polygenic risk scores for MD, bipolar disorder (BD), and schizophrenia (SZ) are associated with depression in the general population and explore whether these polygenic liabilities are associated with heterogeneity in terms of age at onset and severity at the initial depression diagnosis.DESIGN SETTING AND PARTICIPANTS: Participants were drawn from the Danish iPSYCH2012 case-cohort study, a representative sample drawn from the population of Denmark born between May 1, 1981, and December 31, 2005. The 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. The data analysis was conducted from February 2017 to June 2018.EXPOSURES: Polygenic risk scores for MD, BD, and SZ trained using the most recent genome-wide association study results from the Psychiatric Genomics Consortium.MAIN OUTCOMES AND MEASURES: The main outcome was first depressive episode (international Statistical Classification of Diseases and Related Health Problems, Tenth Revision [ICD-10] code F32) treated in hospital-based psychiatric care. Severity at the initial diagnosis was measured using the ICD-10 code severity specifications (mild, moderate, severe without psychosis, and severe with psychosis) and treatment setting (inpatient, outpatient, and emergency).RESULTS: Of 34 573 participants aged 10 to 31 years at censoring, 68% of those with depression were female compared with 48.9% of participants without depression. Each SD increase in polygenic liability for MD, BD, and SZ was associated with 30% (hazard ratio [HR], 1.30; 95% 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 of depression, respectively. Among cases, a higher polygenic liability for BD was associated with earlier depression onset (beta =-.07; SE =.02; P =.002).CONCLUSIONS AND RELEVANCE: Polygenic ability for MD is associated with first depress on in the general population, which supports the idea that these scores tap into an underlying liability for developing the disorder. The fact that polygenic risk for BD and polygenic risk for SZ also were associated with depression is consistent with prior evidence that these disorders share some common genetic overlap. Variations in polygenic liability may contribute slightly to heterogeneity in clinical presentation, but these associations appear minimal.
  • de Jong, Simone, et al. (författare)
  • Applying polygenic risk scoring for psychiatric disorders to a large family with bipolar disorder and major depressive disorder
  • 2018
  • Ingår i: Communications Biology. - Nature Publishing Group. - 2399-3642. ; 1
  • Tidskriftsartikel (refereegranskat)abstract
    • Psychiatric disorders are thought to have a complex genetic pathology consisting of interplay of common and rare variation. Traditionally, pedigrees are used to shed light on the latter only, while here we discuss the application of polygenic risk scores to also highlight patterns of common genetic risk. We analyze polygenic risk scores for psychiatric disorders in a large pedigree (n ~ 260) in which 30% of family members suffer from major depressive disorder or bipolar disorder. Studying patterns of assortative mating and anticipation, it appears increased polygenic risk is contributed by affected individuals who married into the family, resulting in an increasing genetic risk over generations. This may explain the observation of anticipation in mood disorders, whereby onset is earlier and the severity increases over the generations of a family. Joint analyses of rare and common variation may be a powerful way to understand the familial genetics of psychiatric disorders.
  • Huckins, Laura M., et al. (författare)
  • Gene expression imputation across multiple brain regions provides insights into schizophrenia risk
  • 2019
  • Ingår i: Nature genetics. - 1546-1718. ; 51:4, s. 659-
  • Tidskriftsartikel (refereegranskat)abstract
    • Transcriptomic imputation approaches combine eQTL reference panels with large-scale genotype data in order to test associations between disease and gene expression. These genic associations could elucidate signals in complex genome-wide association study (GWAS) loci and may disentangle the role of different tissues in disease development. We used the largest eQTL reference panel for the dorso-lateral prefrontal cortex (DLPFC) to create a set of gene expression predictors and demonstrate their utility. We applied DLPFC and 12 GTEx-brain predictors to 40,299 schizophrenia cases and 65,264 matched controls for a large transcriptomic imputation study of schizophrenia. We identified 413 genic associations across 13 brain regions. Stepwise conditioning identified 67 non-MHC genes, of which 14 did not fall within previous GWAS loci. We identified 36 significantly enriched pathways, including hexosaminidase-A deficiency, and multiple porphyric disorder pathways. We investigated developmental expression patterns among the 67 non-MHC genes and identified specific groups of pre- and postnatal expression.
  • Cantor-Graae, Elizabeth, et al. (författare)
  • Risk for schizophrenia in intercountry adoptees: a Danish population-based cohort study
  • 2007
  • Ingår i: Journal of Child Psychology and Psychiatry and Allied Disciplines. - Wiley-Blackwell. - 1469-7610. ; 48:11, s. 1053-1060
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Increasing numbers of intercountry adoptees are reaching adulthood, the age of onset for most serious mental disorders. Little is known about the development of schizophrenia in intercountry adoptees, a group with potentially increased vulnerability. The aim of this study was to investigate the risk of developing schizophrenia in adoptees and in non-adoptees. Methods: Utilising data from the Danish Civil Registration System, we established a population-based cohort of 1.06 million persons resident in Denmark before the age of 15, whose legal mother lived in Denmark at the child's birth. Intercountry adoptees were identified as children born abroad. Record linkage provided information on psychiatric admissions. Results: Intercountry adoptees had an increased relative risk (RR) (RR = 2.90, 95% CI 2.41-3.50) of developing schizophrenia compared to native Danes. The increased risk was independent of age at onset and age at, or region of, adoption, and was not attributable to mental illness in a foster parent, the foster parent's age, or to urbanisation. The foster mother's own biological offspring had also an increased risk of developing schizophrenia (1.92, 95% Cl 1.23-3.02). Conclusions: Young adult intercountry adoptees are at increased risk for schizophrenia. Although the underlying cause is unknown, a complex interplay of factors presumably may be involved, including heredity, adversity prior to adoption, and post-adoption adjustment difficulties during upbringing.
  • Pedersen, Carsten Bocker, et al. (författare)
  • Do risk factors for schizophrenia predispose to emigration?
  • 2011
  • Ingår i: Schizophrenia Research. - Elsevier. - 0920-9964. ; 127:1-3, s. 229-234
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Increased incidence rates of schizophrenia in immigrants still lack a satisfactory explanation. The aim of this study was to examine the hypothesis that risk factors for schizophrenia also increase the risk of emigration to a foreign country. If valid, Danes emigrating from Denmark carry a higher predisposition to develop schizophrenia compared to Danes living in Denmark. Methods: Utilizing data from the Danish Civil Registration System, we established a population-based cohort of 1.10 million native Danes. We assessed relative risks of emigration to a foreign country in relation to sex, age, urban birth, parental age, and a history of mental illness. Results: Urban birth in Denmark was a significant predictor of emigration to a foreign country. A maternal history of psychiatric contact during childhood and a parental history of bipolar affective disorder increased the risks of emigration. A personal history of mental illness decreased the risk of emigration, mostly for people diagnosed with schizophrenia. Conclusions: Our study provided evidence that Danish emigrants residing in a foreign country have both a higher predisposition of schizophrenia due to differential exposure to birth in urban areas and a lower predisposition of schizophrenia due to differential exposure to a history of mental illness. Although competing selection mechanisms operate, the combined effect of these different selection mechanisms was limited, thus suggesting a potential role for yet to be identified adverse environmental effects operating either before or after emigration. (C) 2011 Elsevier B.V. All rights reserved.
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