{
  "abstract": "Introduction Major depressive disorder (MDD) and Type 2 diabetes (T2D) are serious global health problems with a high degree of co-occurrence. While their bidirectional causal relationship is well-established, only limited studies have considered potential mediators or risk factors.Methods In this study, we used two complementary approaches, first we used genetic data to investigate whether insomnia play the role of mediator in MDD-T2D relationship using both genome-wide association study (GWAS) data and in UK biobank. We applied a range of statistical genetic methods like partial LD-score (LDSC) regression, genetic correlation, Mendelian randomization (MR), two step MR and mediation analysis. Then, using longitudinal electronic health records in Clinical Practice Research Datalink (CPRD), we applied cox proportional hazard model to examine whether a diagnosis of insomnia before or at the time of depression diagnosis increases the T2D risk.Results Results of partial LDSC revealed that the strong genetic correlation between MDD and T2D (rg=0.184, p=3.5E-37) was attenuated when accounting for insomnia (partial_rg: 0.055, p_rg= 1.50E-26). MR demonstrated that a higher genetic liability to both MDD and T2D predicted higher risk of insomnia (OR:1.25, p=9.42E-57; OR: 1.03, p=6.21E-09, respectively). Adjusting for insomnia in the multivariate MR attenuated the bidirectional MDD-T2D relationship. Mediation analysis provided evidence of insomnia being a partial mediator accounting for 36.87% of the total effect of MDD on T2D and 33.52% of the total effect of T2D on MDD. Finally, in longitudinal analyses our preliminary results shows that a diagnosis of insomnia before or at the time of depression diagnosis was associated with an increased risk of developing T2D (Hazard Ratio=1.0586, p=0.005) in depression patients.Conclusion These findings highlight insomnia as an important partial mediator of MDD-T2D relationship and as an independent clinical risk factor. Addressing insomnia may help reduce the burden of these comorbid conditions.",
  "authors": [
    {
      "affiliations": [
        "University of Exeter, Exeter, United Kingdom"
      ],
      "name": "Renu Bala"
    },
    {
      "affiliations": [
        "King’s College London, London, United Kingdom"
      ],
      "name": "Dale Handley"
    },
    {
      "affiliations": [
        "University of Bristol, Bristol, United Kingdom"
      ],
      "name": "Rebecca Richmond"
    },
    {
      "affiliations": [
        "King’s College London, London, United Kingdom"
      ],
      "name": "Cathryn M Lewis"
    },
    {
      "affiliations": [
        "King’s College London, London, United Kingdom"
      ],
      "name": "Alexandra Gillett"
    },
    {
      "affiliations": [
        "University of Exeter, Exeter, United Kingdom"
      ],
      "name": "Jessica Tyrrell"
    }
  ],
  "title": "O11 Using genetic and longitudinal data to understand the role of insomnia in the relationship between major depression and type 2 diabetes",
  "uid": "d9a7b4e8-0602-551a-883a-c4c77b3e6c80"
}