Investigating the shared genetic basis of major depressive disorder (MDD) and type 2 diabetes (T2D).

Major depressive disorder (MDD) and type 2 diabetes (T2D) are often co-morbid. The prevalence of MDD among T2D individuals is twice that of control populations. The exact relationship between T2D and MDD is unknown. T2D may arise as a consequence of poor health behaviors associated with MDD such as poor diet or lack of exercise. Conversely, low mood may arise as a consequence of poor health and the complications of T2D. Alternatively MDD and T2D could both arise from abnormal neuroendocrine function. Few studies have examined the hypothesis that T2D and MDD may share a common genetic basis i.e. genes that increase risk for T2D also effect the risk for MDD. A study of 1237 male twin pairs found the genetic correlation between MDD and T2D to be 0.19 (Scherrer et al, 2011) suggesting some degree of genetic overlap between the trait in males.
The current project proposes to examine further the genetic overlap between T2D and MDD in a family-based population cohort: Generation Scotland: the Scottish Family Health Study (GS:SFHS). This sample comprises ~23,000 individuals with information on personal/family history of diabetes and lifetime diagnosis of MDD. Bivariate heritability analyses will be performed to determine the additive genetic covariance between the traits. The summary data from large genome-wide association studies (GWAS) of MDD and T2D will be used to create polygenic profile scores in ~14,000 genotyped members of GS:SFHS to determine whether common genetic risk variants have shared effects across both disorders (Dudbrige, 2013). Furthermore, Mendelian Randomization (MR) approaches may be used in an attempt to understand the causal relationship between the 2 disorders (Davey-Smith, 2005). MR is a method of using measured variation in genes of known function to examine the causal effect of a modifiable exposure on disease in non-experimental studies – in this instance the effect of T2D on MDD. This will involve the identification of established T2D genetic risk variants from the literature and their association with MDD in GS:SFHS.

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This study will look at the shared aetiology of T2 Diabetes and depression

Scherrer JF, Xian H, Lustman PJ, Franz CE, McCaffery J, Lyons MJ, Jacobson KC, Kremen WS. A Test for Common Genetic and Environmental Vulnerability to Depression and Diabetes. Twin Res Hum Genet. 2011 Apr;14(2):169-72.
Dudbridge F. Power and predictive accuracy of polygenic risk scores. PLoS Genet. 2013 Mar;9(3).
Davey Smith G and Ebrahim S. What can mendelian randomisation tell us about modifiable behavioural and environmental exposures? BMJ. 2005 May 7;330(7499):1076-9.