Genetic comorbidity between major depression and cardio-metabolic traits, stratified by age at onset of major depression

Saskia P. Hagenaars, Jonathan R. I. Coleman, Shing Wan Choi, Héléna Gaspar, Mark J. Adams, David M. Howard, Karen Hodgson, Matthew Traylor, Tracy M. Air, Till F. M. Andlauer, Volker Arolt, Bernhard T. Baune, Elisabeth B. Binder, Douglas H. R. Blackwood, Dorret I. Boomsma, Archie Campbell, Micah Cearns, Darina Czamara, Udo Dannlowski, Katharina DomschkeEco J. C. De Geus, Steven P. Hamilton, Caroline Hayward, Ian B. Hickie, Jouke Jan Hottenga, Marcus Ising, Ian Jones, Lisa Jones, Zoltan Kutalik, Susanne Lucae, Nicholas G. Martin, Yuri Milaneschi, Bertram Mueller‐myhsok, Michael J. Owen, Sandosh Padmanabhan, Brenda W. J. H. Penninx, Giorgio Pistis, David J. Porteous, Martin Preisig, Stephan Ripke, Stanley I. Shyn, Patrick F. Sullivan, John B. Whitfield, Naomi R. Wray, Andrew M. Mcintosh, Ian J. Deary, Gerome Breen, Cathryn M. Lewis, Bertram Mueller-Myhsok

Research output: Contribution to journalArticleAcademicpeer-review

27 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)309-330
Number of pages22
JournalAmerican Journal of Medical Genetics Part B: Neuropsychiatric Genetics
Issue number6
Early online date18 Jul 2020
Publication statusPublished - 1 Sept 2020


  • age at onset
  • cardio-metabolic disease
  • depression
  • genetics
  • polygenic risk scores

Cohort Studies

  • Netherlands Twin Register (NTR)

Cite this