University of Worcester Worcester Research and Publications

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

Musliner, K.L., Mortensen, P.B., McGrath, J.J., Suppli, N.P., Hougaard, D.M., Bybjerg-Grauholm, J., Bækvad-Hansen, M., Andreassen, O.A., Pedersen, C.B., Pedersen, M.G., Mors, O., Nordentoft, M., Børglum, A.D., Werge, T., Agerbo, E., Stahl, E.A., Breen, G., Forstner, A.J., McQuillin, A., Ripke, S., Trubetskoy, V., Mattheisen, M., Wang, Y., Coleman, J.R., Gaspar, H.A., de Leeuw, C.A., Steinberg, S., Whitehead Pavlides, J.M., Trzaskowski, M., Pers, T.H., Holmans, P.A., Abbott, L., Agerbo, E., Akil, H., Albani, D., Alliey-Rodriguez, N., Als, T.D., Anjorin, A., Antilla, V., Awasthi, S., Badner, J.A., Etzekvad-Hansen, M., Barchas, J.D., Bass, N., Bauer, M., Belliveau, R., Bergen, S.E., Pedersen, C.B., Bøen, E., Boks, M., Boocock, J., Budde, M., Bunney, W., Burmeister, M., Bybjerg-Grauholm, J., Byerley, W., Casas, M., Cerrato, F., Cervantes, P., Chambert, K., Chamey, A.W., Chen, D., Churchhouse, C., Clarke, T.K., Coryell, W., Craig, D.W., Cruceanu, C., Curtis, D., Czerski, P.M., Dale, A.M., de Jong, S., Degenhardt, F., Del-Favero, J., DePaulo, J.R., Djurovic, S., Dobbyn, A.L., Dumont, A., Elvsåshagen, T., Escott-Price, V., Fan, C.C., Fischer, S.B., Flickinger, M., Foroud, T.M., Forty, L., Frank, J., Fraser, C., Freimer, N.B., Frisen, L., Gade, K., Gage, D., Garnham, J., Giambartolmei, C., Pedersen, M.G., Goldstein, J., Gordon, S.D., Gordon-Smith, Katherine ORCID:, Green, E.K., Green, M.J., Greenwood, T.A., Grove, J., Guan, W., Parra, J.G., Hamshere, M.L., Hautzinger, M., Heilbronner, U., Herms, S., Hipolito, M., Hoffmann, P., Holland, D., Huckins, L., Jamain, S., Johnson, J.S., Juréus, A., Kandaswamy, R., Karlsson, R., Kennedy, J.L., Kittel-Schneider, S., Knott, Sarah, Knowles, J.A., Kogevinas, M., Koller, A.C., Kupka, R., Lavebratt, C., Lawrence, J., Lawson, W.B., Leber, M., Lee, P.H., Levy, S.E., Li, J.Z., Liu, C., Lucae, S., Maaser, A., MacIntyre, D.J., Mahon, P.B., Maier, W., Martinsson, L., McCarroll, S., McGuffin, P., McInnis, M.G., McKay, J.D., Medeiros, H., Medland, S.E., Meng, F., Milani, L., Montgomery, G.W., Morris, D.W., Muehleisen, T.W., Mullins, N., Nguyen, H., Nievergelt, C.M., Adolfsson, A.N., Nwulia, E.A., O'Donovan, C., Loohuis, L.M.O., Ori, A.P.S., Oruc, L., Osby, U., Perlis, R.H., Perry, Amy ORCID:, Pfennig, A., Potash, J.B., Purcell, S.M., Regeer, E.J., Reif, A., Reinbold, C.S., Rice, J.P., Rivas, F., Rivera, M., Roussos, P., Ruderfer, D.M., Ryu, E., Sánchez-Mora, C., Schatzberg, A.F., Scheftner, W.A., Schork, N.J., Weickert, C.S., Shehktman, T., Shilling, P.D., Sigurdsson, E., Slaney, C., Smeland, O.B., Sobell, J.L., Hansen, C.S., Spijker, A.T., St Clair, D., Steffens, M., Strauss, J.S., Streit, F., Strohmaier, J., Szelinger, S., Thompson, R.C., Thorgeirsson, T.E., Treutlein, J., Vedder, H., Wang, W., Watson, S.J., Weickert, T.W., Witt, S.H., Xi, S., Xu, W., Young, A.H., Zandi, P., Zhang, P., Zollner, S., Agartz, I., Aida, M., Backlund, L., Baune, B.T., Bellivier, F., Berrettini, W.H., Biernacka, J.M., Blackwood, D.H.R., Boehnke, M., Berglum, A.D., Corvin, A., Craddock, N., Daly, M.J., Dannlowski, U., Esko, T., Etain, B., Frye, M., Fullerton, J.M., Gershon, E.S., Goes, F., Grigoroiu-Serbanescu, M., Hauser, J., Hougaard, D.M., Hultman, C.M., Jones, I., Jones, Lisa ORCID:, Kahn, R.S., Kirov, G., Landén, M., Leboyer, M., Lewis, C.M., Li, Q.S., Lissowska, J., Martin, N.G., Mayoral, F., McElroy, S.L., McIntosh, A.M., McMahon, F.J., Melle, I., Metspalu, A., Mitchell, P.B., Morken, G., Mors, O., Mortensen, P.B., Müller-Myhsok, B., Myers, R.M., Neale, B.M., Nimgaonkar, V., Nordentoft, M., Noethen, M.M., O'Donovan, M.C., Oedegaard, K.J., Owen, M., Paciga, S.A., Pato, C., Pato, M.T., Posthuma, D., Ramos-Quiroga, J.A., Ribasés, M., Rietschel, M., Rouleau, G.A., Schalling, M., Schofield, P.R., Schulze, T.G., Serretti, A., Smoller, J.W., Stefansson, H., Stefansson, K., Stordal, E., Sullivan, P.F., Turecki, G., Vaaler, A.E., Ieta, E., Vincent, J.B., Werge, T., Nurnberger, J., Wray, N.R., Di Florio, A., Edenberg, H.J., Cichon, S., Ophoff, R.A., Scott, L.J., Andreassen, O.A., Kelsoe, J. and Sklar, P. (2019) Association of Polygenic Liabilities for Major Depression, Bipolar Disorder, and Schizophrenia With Risk for Depression in the Danish Population. JAMA Psychiatry, 76 (5). pp. 516-525. ISSN Print: 2168-622X Online: 2168-6238

[img] Text
Restricted to Repository staff only

Download (663kB)


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.

Item Type: Article
Additional Information:

The full-text cannot be supplied for this item. Please check availability with your local library or Interlibrary Requests Service.

Uncontrolled Discrete Keywords: polygenic risk, major depression, bipolar disorder, schizophrenia, association with depression in the general population, Denmark, case-cohort study
Divisions: College of Health, Life and Environmental Sciences > School of Allied Health and Community
Related URLs:
Depositing User: Katherine Gordon-Smith
Date Deposited: 02 Jun 2019 07:22
Last Modified: 12 Aug 2020 09:55

Actions (login required)

View Item View Item
Worcester Research and Publications is powered by EPrints 3 which is developed by the School of Electronics and Computer Science at the University of Southampton. More information and software credits.