Investigating shared aetiology between type 2 diabetes and major depressive disorder in a population based cohort

Toni-Kim Clarke, Jana Obsteter, Lynsey S Hall, Caroline Hayward, Pippa A Thomson, Blair H Smith, Sandosh Padmanabhan, Lynne J Hocking, Ian J Deary, David J Porteous, Andrew M McIntosh

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Type II diabetes (T2D) and major depressive disorder (MDD) are often co-morbid. The reasons for this co-morbidity are unclear. Some studies have highlighted the importance of environmental factors and a causal relationship between T2D and MDD has also been postulated. In the present study we set out to investigate the shared aetiology between T2D and MDD using Mendelian randomization in a population based sample, Generation Scotland: the Scottish Family Health Study (N = 21,516). Eleven SNPs found to be associated with T2D were tested for association with MDD and psychological distress (General Health Questionnaire scores). We also assessed causality and genetic overlap between T2D and MDD using polygenic risk scores (PRS) assembled from the largest available GWAS summary statistics to date. No single T2D risk SNP was associated with MDD in the MR analyses and we did not find consistent evidence of genetic overlap between MDD and T2D in the PRS analyses. Linkage disequilibrium score regression analyses supported these findings as no genetic correlation was observed between T2D and MDD (rG = 0.0278 (S.E. 0.11), P-value = 0.79). As suggested by previous studies, T2D and MDD covariance may be better explained by environmental factors. Future studies would benefit from analyses in larger cohorts where stratifying by sex and looking more closely at MDD cases demonstrating metabolic dysregulation is possible. © 2016 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by Wiley Periodicals, Inc.

Original languageEnglish
Pages (from-to)227-234
Number of pages8
JournalAmerican Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
Issue number3
Early online date2 Aug 2016
Publication statusPublished - Apr 2017


  • depression
  • type 2 diabetes
  • genetics
  • polygenic


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