{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T05:56:04Z","timestamp":1790229364741,"version":"4.1.0"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,8,29]],"date-time":"2024-08-29T00:00:00Z","timestamp":1724889600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Extensive observational evidence has suggested an association between depression and type 2 diabetes (T2D). However, the causal relationships between these two diseases require further investigation. This study aimed to evaluate the bidirectional causal effect between two types of depression and T2D using two-sample Mendelian randomization (MR).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We applied two-step MR techniques, using single-nucleotide polymorphisms (SNPs) as the genetic instruments for analysis. We utilized summary data from genome-wide association studies (GWASs) for major depression (MD), depressive status (frequency of depressed mood in the last two weeks), T2D, and other known T2D risk factors such as obesity, sedentary behavior (time spent watching television), and blood pressure. The analysis utilized inverse variance weighted (IVW), MR-Egger regression, weighted median, weighted mode, MR pleiotropy residual sum, and outlier methods to determine potential causal relationships.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The study found that MD was positively associated with T2D, with an odds ratio (OR) of 1.26 (95% CI: 1.10-1.43, p = 5.6\u00d710<jats:sup>-4<\/jats:sup>) using the IVW method and an OR of 1.21 (95% CI: 1.04-1.41, p = 0.01) using the weighted median method. Depressive status was also positively associated with T2D, with an OR of 2.26 (95% CI: 1.03-4.94, p = 0.04) and an OR of 3.62 (95% CI: 1.33-9.90, p = 0.01) using the IVW and weighted median methods, respectively. No causal effects of MD and depressive status on T2D risk factors were observed, and T2D did not influence these factors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our study demonstrates a causal relationship between depression and an increased risk of developing T2D, with both major depression and depressive status being positively associated with T2D.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2024.1436411","type":"journal-article","created":{"date-parts":[[2024,8,29]],"date-time":"2024-08-29T04:38:54Z","timestamp":1724906334000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Depression and type 2 diabetes risk: a Mendelian randomization study"],"prefix":"10.3389","volume":"15","author":[{"given":"Kaiyuan","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diyi","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijun","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sida","family":"Hao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,8,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s40842-016-0039-3","article-title":"Diabetes and its drivers: the largest epidemic in human history","volume":"3","author":"Zimmet","year":"2017","journal-title":"Clin Diabetes Endocrinol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"109119","DOI":"10.1016\/j.diabres.2021.109119","article-title":"IDF Diabetes Atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045","volume":"183","author":"Sun","year":"2022","journal-title":"Diabetes Res Clin Pract"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1111\/jdi.13679","article-title":"Diversity of pathophysiology in type\u20092 diabetes shown by islet pathology","volume":"13","author":"Mizukami","year":"2022","journal-title":"J Diabetes Investig"},{"key":"B4","doi-asserted-by":"publisher","first-page":"7414050","DOI":"10.1155\/2020\/7414050","article-title":"The epidemiology of depression and diabetes distress in type 2 diabetes in Kuwait","volume":"2020","author":"Al-Ozairi","year":"2020","journal-title":"J Diabetes Res"},{"key":"B5","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1007\/s11920-019-0997-0","article-title":"Global burden of disease and the impact of mental and addictive disorders","volume":"21","author":"Rehm","year":"2019","journal-title":"Curr Psychiatry Rep"},{"key":"B6","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1186\/s13690-020-00495-y","article-title":"Are normoglycaemic individuals at risk of depression? The depression-dysglycaemic phenotype from a European population-based cross-sectional study","volume":"78","author":"Cuschieri","year":"2020","journal-title":"Arch Public Health"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-022-05764-9","article-title":"Temporal trends in the prevalence and incidence of depression and the interplay of comorbidities in patients with young- and usual-onset type 2 diabetes from the USA and the UK","volume":"65","author":"Dibato","year":"2022","journal-title":"Diabetologia"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1111\/1753-0407.12968","article-title":"Synergistic effects of depression and obesity on type 2 diabetes incidence in Chinese adults","volume":"12","author":"Ning","year":"2020","journal-title":"J Diabetes"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(13)70139-6","article-title":"Depression and type 2 diabetes: a causal association","volume":"2","author":"Tab\u00e1k","year":"2014","journal-title":"Lancet Diabetes Endocrinol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-021-00414-z","article-title":"The genetics of obesity: from discovery to biology","volume":"23","author":"Loos","year":"2022","journal-title":"Nat Rev Genet"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-020-05253-x","article-title":"An atlas on risk factors for type 2 diabetes: a wide-angled Mendelian randomisation study","volume":"63","author":"Yuan","year":"2020","journal-title":"Diabetologia"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-018-0326-7","article-title":"Genome-wide meta-analysis of depression identifies 102 independent variants and highlights the importance of the prefrontal brain regions","volume":"22","author":"Howard","year":"2019","journal-title":"Nat Neurosci"},{"key":"B13","doi-asserted-by":"publisher","first-page":"2941","DOI":"10.1038\/s41467-018-04951-w","article-title":"Genome-wide association analyses identify 143 risk variants and putative regulatory mechanisms for type 2 diabetes","volume":"9","author":"Xue","year":"2018","journal-title":"Nat Commun"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0205-x","article-title":"Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits","volume":"50","author":"Evangelou","year":"2018","journal-title":"Nat Genet"},{"key":"B15","doi-asserted-by":"publisher","first-page":"k601","DOI":"10.1136\/bmj.k601","article-title":"Reading Mendelian randomisation studies: a guide, glossary, and checklist for clinicians","volume":"362","author":"Davies","year":"2018","journal-title":"BMJ"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1002\/gepi.21758","article-title":"Mendelian randomization analysis with multiple genetic variants using summarized data","volume":"37","author":"Burgess","year":"2013","journal-title":"Genet Epidemiol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyv080","article-title":"Mendelian randomization with invalid instruments: effect estimation and bias detection through Egger regression","volume":"44","author":"Bowden","year":"2015","journal-title":"Int J Epidemiol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1002\/gepi.21965","article-title":"Consistent estimation in mendelian randomization with some invalid instruments using a weighted median estimator","volume":"40","author":"Bowden","year":"2016","journal-title":"Genet Epidemiol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyx102","article-title":"Robust inference in summary data Mendelian randomization via the zero modal pleiotropy assumption","volume":"46","author":"Hartwig","year":"2017","journal-title":"Int J Epidemiol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0099-7","article-title":"Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases","volume":"50","author":"Verbanck","year":"2018","journal-title":"Nat Genet"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyy258","article-title":"Improving the accuracy of two-sample summary-data Mendelian randomization: moving beyond the NOME assumption","volume":"48","author":"Bowden","year":"2019","journal-title":"Int J Epidemiol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyq151","article-title":"Power and instrument strength requirements for Mendelian randomization studies using multiple genetic variants","volume":"40","author":"Pierce","year":"2011","journal-title":"Int J Epidemiol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.34408","article-title":"The MR-Base platform supports systematic causal inference across the human phenome","volume":"7","author":"Hemani","year":"2018","journal-title":"Elife"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyx034","article-title":"MendelianRandomization: an R package for performing Mendelian randomization analyses using summarized data","volume":"46","author":"Yavorska","year":"2017","journal-title":"Int J Epidemiol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/S2666-7568(22)00291-4","article-title":"Association of type 2 diabetes according to the number of risk factors within the recommended range with incidence of major depression and clinically relevant depressive symptoms: a prospective analysis","volume":"4","author":"van Gennip","year":"2023","journal-title":"Lancet Healthy Longev"},{"key":"B26","doi-asserted-by":"publisher","first-page":"13575","DOI":"10.1038\/s41598-021-92963-w","article-title":"Depression-related weight change and incident diabetes in a community sample","volume":"11","author":"Graham","year":"2021","journal-title":"Sci Rep"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1111\/dme.14399","article-title":"Understanding the relationship between type 2 diabetes and depression: lessons from genetically informative study designs","volume":"38","author":"Bergmans","year":"2021","journal-title":"Diabetes Med"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-22-0466","article-title":"Risk factors associated with mortality among individuals with type 2 diabetes and depression across two cohorts","volume":"187","author":"Rohde","year":"2022","journal-title":"Eur J Endocrinol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1007\/s00592-021-01791-x","article-title":"Is it time to consider depression as a major complication of type 2 diabetes? Evidence from a large population-based cohort study","volume":"59","author":"Messina","year":"2022","journal-title":"Acta Diabetol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1111\/j.1525-1497.2004.30405.x","article-title":"Cardiac risk factors in patients with diabetes mellitus and major depression","volume":"19","author":"Katon","year":"2004","journal-title":"J Gen Intern Med"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.2147\/PRBM.S396916","article-title":"Mediating role of depression between diabetes management self-efficacy and diabetes self-care behavior among elderly type 2 diabetes mellitus patients in China","volume":"16","author":"Jiang","year":"2023","journal-title":"Psychol Res Behav Manage"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1111\/jocn.15741","article-title":"Association between subthreshold depression and self-care behaviours in adults with type 2 diabetes: A cross-sectional study","volume":"30","author":"Shrestha","year":"2021","journal-title":"J Clin Nurs"},{"key":"B33","doi-asserted-by":"publisher","first-page":"1298","DOI":"10.3390\/brainsci11101298","article-title":"HPA axis in the pathomechanism of depression and schizophrenia: new therapeutic strategies based on its participation","volume":"11","author":"Mikulska","year":"2021","journal-title":"Brain Sci"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1055\/s-2000-7742","article-title":"Major depression and impaired glucose tolerance","volume":"108","author":"Weber","year":"2000","journal-title":"Exp Clin Endocrinol Diabetes"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/j.psym.2017.11.003","article-title":"Prevalence and risk factors of type 2 diabetes in major depression: A study on 703 individuals referred for sleep examinations","volume":"59","author":"Hein","year":"2018","journal-title":"Psychosomatics"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1080\/13651501.2021.1957117","article-title":"Diabetes and mood disorders: shared mechanisms and therapeutic opportunities","volume":"26","author":"Martins","year":"2022","journal-title":"Int J Psychiatry Clin Pract"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.13699","article-title":"Detecting a potential safety signal of antidepressants and type 2 diabetes: a pharmacovigilance-pharmacodynamic study","volume":"84","author":"Siafis","year":"2018","journal-title":"Br J Clin Pharmacol"},{"key":"B38","doi-asserted-by":"publisher","first-page":"105715","DOI":"10.1016\/j.psyneuen.2022.105715","article-title":"Diabetes, antidiabetic medications and risk of depression - A population-based cohort and nested case-control study","volume":"140","author":"Wium-Andersen","year":"2022","journal-title":"Psychoneuroendocrinology"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2024.1436411\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,29]],"date-time":"2024-08-29T04:38:56Z","timestamp":1724906336000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2024.1436411\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,29]]},"references-count":38,"alternative-id":["10.3389\/fendo.2024.1436411"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2024.1436411","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,29]]},"article-number":"1436411"}}