Esben Agerbo1,2,3, Betina B Trabjerg1,2,3, Anders D Børglum1,4,5, Andrew J Schork1,6,7, Bjarni J Vilhjálmsson1,2, Carsten B Pedersen1,2,3, Christian Hakulinen8, Clara Albiñana1,2, David M Hougaard1,9, Jakob Grove1,4,5,10, John J McGrath2,11,12, Jonas Bybjerg-Grauholm1,9, Ole Mors1,13, Oleguer Plana-Ripoll1, Thomas Werge1,7,14,15, Naomi R Wray16, Preben Bo Mortensen1,2,3, Katherine L Musliner1,2,3. 1. Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Aarhus, Denmark. 2. National Centre for Register-Based Research (NCRR), Aarhus University, Aarhus, Denmark. 3. Centre for Integrated Register-based Research at Aarhus University (CIRRAU), Aarhus, Denmark. 4. Department of Biomedicine and Center for Integrative Sequencing (iSEQ), Aarhus University, Aarhus, Denmark. 5. Center for Genomics and Personalized Medicine, Aarhus University, Aarhus, Denmark. 6. Neurogenomics Division, Translational Genomics Research Institute, Phoenix, Arizona. 7. Institute of Biological Psychiatry, Mental Health Center Sct Hans, Roskilde, Denmark. 8. Department of Psychology and Logopedics, University of Helsinki, Helsinki, Finland. 9. Department for Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark. 10. Bioinformatics Research Centre, Aarhus University, Aarhus, Denmark. 11. Queensland Brain Institute, University of Queensland, St Lucia, Queensland, Australia. 12. Queensland Centre for Mental Health Research, The Park Centre for Mental Health, Wacol, Queensland, Australia. 13. Psychosis Research Unit, Aarhus University Hospital-Psychiatry, Aarhus, Denmark. 14. Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. 15. Center for GeoGenetic, GLOBE Institute, University of Copenhagen, Copenhagen, Denmark. 16. Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.
Abstract
Importance: Combining information on polygenic risk scores (PRSs) with other known risk factors could potentially improve the identification of risk of depression in the general population. However, to our knowledge, no study has estimated the association of PRS with the absolute risk of depression, and few have examined combinations of the PRS and other important risk factors, including parental history of psychiatric disorders and socioeconomic status (SES), in the identification of depression risk. Objective: To assess the individual and joint associations of PRS, parental history, and SES with relative and absolute risk of early-onset depression. Design, Setting, and Participants: This case-cohort study included participants from the iPSYCH2012 sample, a case-cohort sample of all singletons born in Denmark between May 1, 1981, and December 31, 2005. Hazard ratios (HRs) and absolute risks were estimated using Cox proportional hazards regression for case-cohort designs. Exposures: The PRS for depression; SES measured using maternal educational level, maternal marital status, and paternal employment; and parental history of psychiatric disorders (major depression, bipolar disorder, other mood or psychotic disorders, and other psychiatric diagnoses). Main Outcomes and Measures: Hospital-based diagnosis of depression from inpatient, outpatient, or emergency settings. Results: Participants included 17 098 patients with depression (11 748 [68.7%] female) and 18 582 (9429 [50.7%] male) individuals randomly selected from the base population. The PRS, parental history, and lower SES were all significantly associated with increased risk of depression, with HRs ranging from 1.32 (95% CI, 1.29-1.35) per 1-SD increase in PRS to 2.23 (95% CI, 1.81-2.64) for maternal history of mood or psychotic disorders. Fully adjusted models had similar effect sizes, suggesting that these risk factors do not confound one another. Absolute risk of depression by the age of 30 years differed substantially, depending on an individual's combination of risk factors, ranging from 1.0% (95% CI, 0.1%-2.0%) among men with high SES in the bottom 2% of the PRS distribution to 23.7% (95% CI, 16.6%-30.2%) among women in the top 2% of PRS distribution with a parental history of psychiatric disorders. Conclusions and Relevance: This study suggests that current PRSs for depression are not more likely to be associated with major depressive disorder than are other known risk factors; however, they may be useful for the identification of risk in conjunction with other risk factors.
Importance: Combining information on polygenic risk scores (PRSs) with other known risk factors could potentially improve the identification of risk of depression in the general population. However, to our knowledge, no study has estimated the association of PRS with the absolute risk of depression, and few have examined combinations of the PRS and other important risk factors, including parental history of psychiatric disorders and socioeconomic status (SES), in the identification of depression risk. Objective: To assess the individual and joint associations of PRS, parental history, and SES with relative and absolute risk of early-onset depression. Design, Setting, and Participants: This case-cohort study included participants from the iPSYCH2012 sample, a case-cohort sample of all singletons born in Denmark between May 1, 1981, and December 31, 2005. Hazard ratios (HRs) and absolute risks were estimated using Cox proportional hazards regression for case-cohort designs. Exposures: The PRS for depression; SES measured using maternal educational level, maternal marital status, and paternal employment; and parental history of psychiatric disorders (major depression, bipolar disorder, other mood or psychotic disorders, and other psychiatric diagnoses). Main Outcomes and Measures: Hospital-based diagnosis of depression from inpatient, outpatient, or emergency settings. Results: Participants included 17 098 patients with depression (11 748 [68.7%] female) and 18 582 (9429 [50.7%] male) individuals randomly selected from the base population. The PRS, parental history, and lower SES were all significantly associated with increased risk of depression, with HRs ranging from 1.32 (95% CI, 1.29-1.35) per 1-SD increase in PRS to 2.23 (95% CI, 1.81-2.64) for maternal history of mood or psychotic disorders. Fully adjusted models had similar effect sizes, suggesting that these risk factors do not confound one another. Absolute risk of depression by the age of 30 years differed substantially, depending on an individual's combination of risk factors, ranging from 1.0% (95% CI, 0.1%-2.0%) among men with high SES in the bottom 2% of the PRS distribution to 23.7% (95% CI, 16.6%-30.2%) among women in the top 2% of PRS distribution with a parental history of psychiatric disorders. Conclusions and Relevance: This study suggests that current PRSs for depression are not more likely to be associated with major depressive disorder than are other known risk factors; however, they may be useful for the identification of risk in conjunction with other risk factors.
Authors: Stacey Pereira; Katrina A Muñoz; Brent J Small; Takahiro Soda; Laura N Torgerson; Clarissa E Sanchez; Jehannine Austin; Eric A Storch; Gabriel Lázaro-Muñoz Journal: Am J Med Genet B Neuropsychiatr Genet Date: 2022-07-06 Impact factor: 3.358
Authors: Emil M Pedersen; Esben Agerbo; Oleguer Plana-Ripoll; Jakob Grove; Julie W Dreier; Katherine L Musliner; Marie Bækvad-Hansen; Georgios Athanasiadis; Andrew Schork; Jonas Bybjerg-Grauholm; David M Hougaard; Thomas Werge; Merete Nordentoft; Ole Mors; Søren Dalsgaard; Jakob Christensen; Anders D Børglum; Preben B Mortensen; John J McGrath; Florian Privé; Bjarni J Vilhjálmsson Journal: Am J Hum Genet Date: 2022-02-08 Impact factor: 11.025