Department of Economics and Business Economics

Association of Polygenic Liabilities for Major Depression, Bipolar Disorder, and Schizophrenia With Risk for Depression in the Danish Population

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Association of Polygenic Liabilities for Major Depression, Bipolar Disorder, and Schizophrenia With Risk for Depression in the Danish Population. / Musliner, Katherine L; Mortensen, Preben B; McGrath, John J; Suppli, Nis P; Hougaard, David M; Bybjerg-Grauholm, Jonas; Bækvad-Hansen, Marie; Andreassen, Ole; Pedersen, Carsten B; Pedersen, Marianne G; Mors, Ole; Nordentoft, Merete; Børglum, Anders D; Werge, Thomas; Agerbo, Esben; Bipolar Disorder Working Group of the Psychiatric Genomics Consortium.

In: JAMA Psychiatry, Vol. 76, No. 5, 05.2019, p. 516-525.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Harvard

Musliner, KL, Mortensen, PB, McGrath, JJ, Suppli, NP, Hougaard, DM, Bybjerg-Grauholm, J, Bækvad-Hansen, M, Andreassen, O, Pedersen, CB, Pedersen, MG, Mors, O, Nordentoft, M, Børglum, AD, Werge, T, Agerbo, E & Bipolar Disorder Working Group of the Psychiatric Genomics Consortium 2019, 'Association of Polygenic Liabilities for Major Depression, Bipolar Disorder, and Schizophrenia With Risk for Depression in the Danish Population', JAMA Psychiatry, vol. 76, no. 5, pp. 516-525. https://doi.org/10.1001/jamapsychiatry.2018.4166

APA

Musliner, K. L., Mortensen, P. B., McGrath, J. J., Suppli, N. P., Hougaard, D. M., Bybjerg-Grauholm, J., Bækvad-Hansen, M., Andreassen, O., Pedersen, C. B., Pedersen, M. G., Mors, O., Nordentoft, M., Børglum, A. D., Werge, T., Agerbo, E., & Bipolar Disorder Working Group of the Psychiatric Genomics Consortium (2019). Association of Polygenic Liabilities for Major Depression, Bipolar Disorder, and Schizophrenia With Risk for Depression in the Danish Population. JAMA Psychiatry, 76(5), 516-525. https://doi.org/10.1001/jamapsychiatry.2018.4166

CBE

Musliner KL, Mortensen PB, McGrath JJ, Suppli NP, Hougaard DM, Bybjerg-Grauholm J, Bækvad-Hansen M, Andreassen O, Pedersen CB, Pedersen MG, Mors O, Nordentoft M, Børglum AD, Werge T, Agerbo E, Bipolar Disorder Working Group of the Psychiatric Genomics Consortium. 2019. Association of Polygenic Liabilities for Major Depression, Bipolar Disorder, and Schizophrenia With Risk for Depression in the Danish Population. JAMA Psychiatry. 76(5):516-525. https://doi.org/10.1001/jamapsychiatry.2018.4166

MLA

Vancouver

Author

Musliner, Katherine L ; Mortensen, Preben B ; McGrath, John J ; Suppli, Nis P ; Hougaard, David M ; Bybjerg-Grauholm, Jonas ; Bækvad-Hansen, Marie ; Andreassen, Ole ; Pedersen, Carsten B ; Pedersen, Marianne G ; Mors, Ole ; Nordentoft, Merete ; Børglum, Anders D ; Werge, Thomas ; Agerbo, Esben ; Bipolar Disorder Working Group of the Psychiatric Genomics Consortium. / Association of Polygenic Liabilities for Major Depression, Bipolar Disorder, and Schizophrenia With Risk for Depression in the Danish Population. In: JAMA Psychiatry. 2019 ; Vol. 76, No. 5. pp. 516-525.

Bibtex

@article{f79821d443ba4f64aa7ec487875f40ba,
title = "Association of Polygenic Liabilities for Major Depression, Bipolar Disorder, and Schizophrenia With Risk for Depression in the Danish Population",
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 (β = -.07; SE = .02; P = .002).Conclusions and Relevance: Polygenic liability for MD is associated with first depression 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.",
author = "Musliner, {Katherine L} and Mortensen, {Preben B} and McGrath, {John J} and Suppli, {Nis P} and Hougaard, {David M} and Jonas Bybjerg-Grauholm and Marie B{\ae}kvad-Hansen and Ole Andreassen and Pedersen, {Carsten B} and Pedersen, {Marianne G} and Ole Mors and Merete Nordentoft and B{\o}rglum, {Anders D} and Thomas Werge and Esben Agerbo and {Bipolar Disorder Working Group of the Psychiatric Genomics Consortium}",
year = "2019",
month = may,
doi = "10.1001/jamapsychiatry.2018.4166",
language = "English",
volume = "76",
pages = "516--525",
journal = "J A M A Psychiatry",
issn = "0003-990X",
publisher = "The JAMA Network",
number = "5",

}

RIS

TY - JOUR

T1 - Association of Polygenic Liabilities for Major Depression, Bipolar Disorder, and Schizophrenia With Risk for Depression in the Danish Population

AU - Musliner, Katherine L

AU - Mortensen, Preben B

AU - McGrath, John J

AU - Suppli, Nis P

AU - Hougaard, David M

AU - Bybjerg-Grauholm, Jonas

AU - Bækvad-Hansen, Marie

AU - Andreassen, Ole

AU - Pedersen, Carsten B

AU - Pedersen, Marianne G

AU - Mors, Ole

AU - Nordentoft, Merete

AU - Børglum, Anders D

AU - Werge, Thomas

AU - Agerbo, Esben

AU - Bipolar Disorder Working Group of the Psychiatric Genomics Consortium

PY - 2019/5

Y1 - 2019/5

N2 - 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 (β = -.07; SE = .02; P = .002).Conclusions and Relevance: Polygenic liability for MD is associated with first depression 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.

AB - 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 (β = -.07; SE = .02; P = .002).Conclusions and Relevance: Polygenic liability for MD is associated with first depression 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.

U2 - 10.1001/jamapsychiatry.2018.4166

DO - 10.1001/jamapsychiatry.2018.4166

M3 - Journal article

C2 - 30698613

VL - 76

SP - 516

EP - 525

JO - J A M A Psychiatry

JF - J A M A Psychiatry

SN - 0003-990X

IS - 5

ER -