J Zhang, Z K Chen, R D Triatin, H Snieder, C H L Thio, C A Hartman
{"title":"注意缺陷多动障碍与 2 型糖尿病之间的中介途径：来自两步多变量孟德尔随机研究的证据。","authors":"J Zhang, Z K Chen, R D Triatin, H Snieder, C H L Thio, C A Hartman","doi":"10.1017/S2045796024000593","DOIUrl":null,"url":null,"abstract":"<p><strong>Aims: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":11787,"journal":{"name":"Epidemiology and Psychiatric Sciences","volume":"33 ","pages":"e54"},"PeriodicalIF":5.9000,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11561680/pdf/","citationCount":"0","resultStr":"{\"title\":\"Mediating pathways between attention deficit hyperactivity disorder and type 2 diabetes mellitus: evidence from a two-step and multivariable Mendelian randomization study.\",\"authors\":\"J Zhang, Z K Chen, R D Triatin, H Snieder, C H L Thio, C A Hartman\",\"doi\":\"10.1017/S2045796024000593\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Aims: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>\",\"PeriodicalId\":11787,\"journal\":{\"name\":\"Epidemiology and Psychiatric Sciences\",\"volume\":\"33 \",\"pages\":\"e54\"},\"PeriodicalIF\":5.9000,\"publicationDate\":\"2024-10-28\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11561680/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Epidemiology and Psychiatric Sciences\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1017/S2045796024000593\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PSYCHIATRY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Epidemiology and Psychiatric Sciences","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1017/S2045796024000593","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PSYCHIATRY","Score":null,"Total":0}
Mediating pathways between attention deficit hyperactivity disorder and type 2 diabetes mellitus: evidence from a two-step and multivariable Mendelian randomization study.
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.
期刊介绍：
Epidemiology and Psychiatric Sciences is a prestigious international, peer-reviewed journal that has been publishing in Open Access format since 2020. Formerly known as Epidemiologia e Psichiatria Sociale and established in 1992 by Michele Tansella, the journal prioritizes highly relevant and innovative research articles and systematic reviews in the areas of public mental health and policy, mental health services and system research, as well as epidemiological and social psychiatry. Join us in advancing knowledge and understanding in these critical fields.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
