Genetic overlap between type 2 diabetes and depression in Swedish and Danish twin registries.

C Kan,S R Bornstein,J H Maccabe,J Licinio,N L Pedersen,K Christensen,K Ismail,F Rijsdijk

doi:10.1038/mp.2016.28

Abstract

A bidirectional association between type 2 diabetes (T2DM) and depression has been consistently reported. Depression is associated with worse biomedical outcomes and increased mortality. The mechanisms underlying the association of T2DM with depression remain unclear. One possible question we can address is the extent to which the co-occurrence of diabetes and depression is due to correlated genetic and/or environmental risk factors. In this study, we performed structural equation model fitting to population-level data from the Swedish (n=68 606) and Danish (n=95 403) twin registries. The primary outcomes were clinical diagnosis of T2DM and depression using national hospital discharge registries. The phenotypic correlation between T2DM and depression is modest in both samples. In the Swedish sample, unique environmental effects explain a greater proportion of the covariance in males, whereas the association is primarily attributed to genetic effects in females. In the Danish sample, genetic effects account for the majority of the covariance in both males and females. Qualitative genetic sex differences are observed in both samples. We believe this is the first study to demonstrate significant genetic overlap between T2DM and depression.

Highlights

Cross-sectional and longitudinal studies have consistently reported an association between type 2 diabetes (T2DM) and depression,[1,2] with up to 60% increased risk for developing T2DM in individuals with depression and 15% increased risk for incident depression in those with T2DM.[3,4] Depression has been associated with adverse effects on diabetes outcomes including suboptimal glycaemic control, complications and higher rates of mortality.Tentative evidence suggests a common biological pathway between T2DM and depression, as people with depression have increased levels of inflammation, hyperactivity in the hypothalamic–pituitary adrenal axis and sympathetic nervous system.[5]
The Screening Across the Lifespan Twin (SALT) cohort consists of twins born between 1886 and 1958,13,14 whereas the Studies of Adults: Genes and Environment (STAGE) cohort consists of twins born between 1959 and 1985.15 The project was approved by the Regional Research Ethics Board at Karolinska Institute and the Steering Board of the Swedish Twin Registry
The Swedish Twin Registry from the SALT and STAGE cohorts consists of 68 606 twin individuals with known age, sex, zygosity, T2DM and depression

Summary

Introduction

Tentative evidence suggests a common biological pathway between T2DM and depression, as people with depression have increased levels of inflammation, hyperactivity in the hypothalamic–pituitary adrenal axis and sympathetic nervous system.[5] Those biological processes underlie T2DM.[6]. A significant genetic correlation between T2DM and depression would provide evidence in support of a common genetic pathway to both disorders. It is known that genetic factors are aetiologically important in both T2DM and depression, it is unclear to what extent the T2DM-depression association correlated genetic or environmental factors. Twin studies provide a valuable approach to investigate genetic influences on complex traits or disorders,[7] as well as the genetic architecture of comorbidity

Methods

Results

Discussion

Conclusion