American Diabetes Association
Supplemental_Materials_Familial_Liability_T2D_Psy_RV3.pdf (293.9 kB)

Early-onset type 2 diabetes and mood, anxiety, and stress-related disorders: a genetically informative register-based cohort study

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posted on 2022-10-17, 16:11 authored by Shengxin Liu, Marica Leone, Jonas F. Ludvigsson, Paul Lichtenstein, Soffia Gudbjörnsdottir, Mikael Landén, Sarah E. Bergen, Mark J. Taylor, Henrik Larsson, Ralf Kuja-Halkola, Agnieszka Butwicka



To assess the association and familial co-aggregation between early-onset type 2 diabetes (diagnosed before age 45) and mood, anxiety, and stress-related disorders, and estimate the contribution of genetic and environmental factors to their co-occurrence. 

Research Design and Methods

This population-based cohort study included individuals born in Sweden 1968-1998, from whom pairs of full-siblings, half-siblings, and cousins were identified. Diagnoses of early-onset type 2 diabetes and mood (including unipolar depression and bipolar disorder), anxiety, and stress-related disorders were obtained from the National Patient Register. Logistic and Cox regression models were used to assess the phenotypic association and familial co-aggregation between type 2 diabetes and psychiatric disorders. Quantitative genetic modeling was conducted in full- and maternal half-sibling pairs to estimate the relative contributions of genetic and environmental factors to the association. 


Among a total of 3,061,192 individuals, 7,896(0.3%) were diagnosed with early-onset type 2 diabetes. These individuals showed higher risks of any diagnosis (Odds Ratio [OR][95%CI]: 3.62[3.44,3.80]) and specific diagnosis of unipolar depression (3.97[3.75,4.22]), bipolar disorder (4.17[3.68,4.73]), anxiety (3.76[3.54,3.99]) and stress-related disorders (3.35[3.11,3.61]). Relatives of individuals with early-onset type 2 diabetes also had higher overall risks of the examined psychiatric disorders (ORs:1.03-1.57). These associations are largely explained by genetic factors (51%-78%), with the rest explained by non-shared environmental factors. 


Our findings highlight the burden of mood, anxiety, and stress-related disorders in early-onset type 2 diabetes and demonstrate that shared familial liability may contribute to their co-occurrence, suggesting that future research should aim to identify shared risk factors and ultimately refine preventive and intervention strategies.  


Financial support was provided through the Swedish Research Council (No 2017-00788) and Karolinska Institutet, Strategic Research Program in Neuroscience (StratNeuro). A.B. was also supported by the Stockholm County Council (clinical research appointment 20180718) while working on this project. M.Leone received funding from the EU's Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement number 721567.