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Genetic comorbidity between major depression and cardiometabolic traits, stratified by age at onset of major depression

Hagenaars, S., Coleman, J., Wan Choi, S., Gaspar, H., Adams, M., Howard, D., Hodgson, K., Traylor, M., Air, T., Andlauer, T., Arolt, V., Baune, B., Binder, E., Blackwood, D., Boomsma, D., Campbell, A., Cearns, M., Czamara, D., Dannlowski, U., Domschke, K., de Geua, E., Hamilton, S., Hayward, C., Hickie, I., Hottenga, J., Ising, M., Jones, I., Jones, Lisa ORCID: https://orcid.org/0000-0002-5122-8334, Kutalik, Z., Lucae, S., Martin, N., Milaneschi, Y., Mueller-Myhsok, B., Owen, M., Padmanabham, S., Penninx, B., Pistis, G., Porteous, D., Presig, M., Ripke, S., Shyn, S., Sullivan, P., Whitfield, J., Wray, N., McIntosh, A., Deary, I., Breen, G. and Lewis, C. (2020) Genetic comorbidity between major depression and cardiometabolic traits, stratified by age at onset of major depression. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics. ISSN Online: 1552-485X (In Press)

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Abstract

It is imperative to understand the specific and shared etiologies of major depression and cardio-metabolic disease, as both traits are frequently comorbid and each represents a major burden to society. This study examined whether there is a genetic association between major depression and cardio-metabolic traits and if this association is stratified by age at onset for major depression. Polygenic risk scores analysis and linkage disequilibrium score regression was performed to examine whether differences in shared genetic etiology exist between depression case control status (N cases = 40,940, N controls = 67,532), earlier (N = 15,844), and later onset depression (N = 15,800) with body mass index, coronary artery disease, stroke, and type 2 diabetes in 11 data sets from the Psychiatric Genomics Consortium, Generation Scotland, and UK Biobank. All cardio-metabolic polygenic risk scores were associated with depression status. Significant genetic correlations were found between depression and body mass index, coronary artery disease, and type 2 diabetes. Higher polygenic risk for body mass index, coronary artery disease, and type 2 diabetes was associated with both early and later onset depression, while higher polygenic risk for stroke was associated with later onset depression only. Significant genetic correlations were found between body mass index and later onset depression, and between coronary artery disease and both early and late onset depression. The phenotypic associations between major depression and cardio-metabolic traits may partly reflect
their overlapping genetic etiology irrespective of the age depression first presents.

Item Type: Article
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This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

© 2020 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics published by Wiley Periodicals LLC

Uncontrolled Discrete Keywords: age at onset, cardi-metabolic disease, depression, genetics, polygenic risk scores
Subjects: R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Divisions: College of Health, Life and Environmental Sciences > School of Allied Health and Community
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Copyright Info: Open Access article
Depositing User: Katherine Gordon-Smith
Date Deposited: 04 Aug 2020 12:46
Last Modified: 04 Aug 2020 12:46
URI: https://eprints.worc.ac.uk/id/eprint/9591

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