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Epidemiology and Psychiatric Sciences
Article . 2024 . Peer-reviewed
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Mediating pathways between attention deficit hyperactivity disorder and type 2 diabetes mellitus: evidence from a two-step and multivariable Mendelian randomization study

evidence from a two-step and multivariable Mendelian randomization study
Authors: Zhang, J.; Chen, Z. K.; Triatin, R. D.; Snieder, H.; Thio, C. H. L.; Hartman, C. A.;

Mediating pathways between attention deficit hyperactivity disorder and type 2 diabetes mellitus: evidence from a two-step and multivariable Mendelian randomization study

Abstract

Abstract Aims Type 2 diabetes (T2D) is a global health burden, more prevalent among individuals with attention deficit hyperactivity disorder (ADHD) compared to the general population. To extend the knowledge base on how ADHD links to T2D, this study aimed to estimate causal effects of ADHD on T2D and to explore mediating pathways. Methods We applied a two-step, two-sample Mendelian randomization (MR) design, using single nucleotide polymorphisms to genetically predict ADHD and a range of potential mediators. First, a wide range of univariable MR methods was used to investigate associations between genetically predicted ADHD and T2D, and between ADHD and the purported mediators: body mass index (BMI), childhood obesity, childhood BMI, sedentary behaviour (daily hours of TV watching), blood pressure (systolic blood pressure, diastolic blood pressure), C-reactive protein and educational attainment (EA). A mixture-of-experts method was then applied to select the MR method most likely to return a reliable estimate. We used estimates derived from multivariable MR to estimate indirect effects of ADHD on T2D through mediators. Results Genetically predicted ADHD liability associated with 10% higher odds of T2D (OR: 1.10; 95% CI: 1.02, 1.18). From nine purported mediators studied, three showed significant individual mediation effects: EA (39.44% mediation; 95% CI: 29.00%, 49.73%), BMI (44.23% mediation; 95% CI: 34.34%, 52.03%) and TV watching (44.10% mediation; 95% CI: 30.76%, 57.80%). The combination of BMI and EA explained the largest mediating effect (53.31%, 95% CI: −1.99%, 110.38%) of the ADHD–T2D association. Conclusions These findings suggest a potentially causal, positive relationship between ADHD liability and T2D, with mediation through higher BMI, more TV watching and lower EA. Intervention on these factors may thus have beneficial effects on T2D risk in individuals with ADHD.

Keywords

Type 2/genetics, Male, Pediatric Obesity, Blood Pressure/genetics, Neurosciences. Biological psychiatry. Neuropsychiatry, Blood Pressure, Polymorphism, Single Nucleotide, Body Mass Index, SDG 3 - Good Health and Well-being, Risk Factors, Pediatric Obesity/genetics, Diabetes Mellitus, health outcomes, Humans, Genetic Predisposition to Disease, Polymorphism, Child, Single Nucleotide, Mendelian Randomization Analysis, chronic conditions, attention deficit hyperactivity disorder, Diabetes Mellitus, Type 2, Attention Deficit Disorder with Hyperactivity, Original Article, Female, Public aspects of medicine, RA1-1270, Sedentary Behavior, Attention Deficit Disorder with Hyperactivity/genetics, metabolism, RC321-571

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
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