Nat Na-Ek1,2, Juthamanee Srithong3, Authakorn Aonkhum3, Suthida Boonsom3,4, Pimphen Charoen5,6, Panayotes Demakakos7. 1. Department of Pharmaceutical Care, School of Pharmaceutical Sciences, University of Phayao, Phayao, 56000, Thailand. nat.na@up.ac.th. 2. Unit of Excellence On Research in Health Outcomes and Patient Safety in Elderly (U-R-HOPE), School of Pharmaceutical Sciences, University of Phayao, Phayao, 56000, Thailand. nat.na@up.ac.th. 3. Department of Pharmaceutical Care, School of Pharmaceutical Sciences, University of Phayao, Phayao, 56000, Thailand. 4. Unit of Excellence On Pharmacogenomic Pharmacokinetic and Pharmacotherapeutic Researches (UPPER), School of Pharmaceutical Sciences, University of Phayao, Phayao, 56000, Thailand. 5. Department of Tropical Hygiene, Faculty of Tropical Medicine, Mahidol University, Bangkok, 10400, Thailand. 6. Integrative Computational BioScience (ICBS) Center, Mahidol University, Bangkok, 10400, Thailand. 7. Department of Epidemiology and Public Health, University College London, London, WC1E 7HB, UK.
Abstract
BACKGROUND AND OBJECTIVE: Education might be causal to type 2 diabetes mellitus (T2DM). We triangulated cohort and genetic evidence to consolidate the causality between education and T2DM. METHODS: We obtained observational evidence from the English Longitudinal Study of Ageing (ELSA). Self-reporting educational attainment was categorised as high (post-secondary and higher), middle (secondary), and low (below secondary or no academic qualifications) in 6,786 community-dwelling individuals aged ≥ 50 years without diabetes at ELSA wave 2, who were followed until wave 8 for the first diabetes diagnosis. Additionally, we performed two-sample Mendelian randomisation (MR) using an inverse-variance weighted (IVW), MR-Egger, weighted median (WM), and weighted mode-based estimate (WMBE) method. Steiger filtering was further applied to exclude single-nucleotide polymorphisms (SNPs) that were correlated with an outcome (T2DM) stronger than exposure (education attainment). RESULTS: We observed 598 new diabetes cases after 10.4 years of follow-up. The adjusted hazard ratios (95% CI) of T2DM were 1.20 (0.97-1.49) and 1.58 (1.28-1.96) in the middle- and low-education groups, respectively, compared to the high-education group. Low education was also associated with increased glycated haemoglobin levels. Psychosocial resources, occupation, and health behaviours fully explained these inverse associations. In the MR analysis of 210 SNPs (R2 = 0.0161), the odds ratio of having T2DM per standard deviation-decreasing years (4.2 years) of schooling was 1.33 (1.01-1.75; IVW), 1.23 (0.37-4.17; MR-Egger), 1.56 (1.09-2.27; WM), and 2.94 (0.98-9.09; WMBE). However, applying Steiger filtering attenuated most MR results towards the null. CONCLUSIONS: Our inconsistent findings between cohort and genetic evidence did not support the causality between education and T2DM.
BACKGROUND AND OBJECTIVE: Education might be causal to type 2 diabetes mellitus (T2DM). We triangulated cohort and genetic evidence to consolidate the causality between education and T2DM. METHODS: We obtained observational evidence from the English Longitudinal Study of Ageing (ELSA). Self-reporting educational attainment was categorised as high (post-secondary and higher), middle (secondary), and low (below secondary or no academic qualifications) in 6,786 community-dwelling individuals aged ≥ 50 years without diabetes at ELSA wave 2, who were followed until wave 8 for the first diabetes diagnosis. Additionally, we performed two-sample Mendelian randomisation (MR) using an inverse-variance weighted (IVW), MR-Egger, weighted median (WM), and weighted mode-based estimate (WMBE) method. Steiger filtering was further applied to exclude single-nucleotide polymorphisms (SNPs) that were correlated with an outcome (T2DM) stronger than exposure (education attainment). RESULTS: We observed 598 new diabetes cases after 10.4 years of follow-up. The adjusted hazard ratios (95% CI) of T2DM were 1.20 (0.97-1.49) and 1.58 (1.28-1.96) in the middle- and low-education groups, respectively, compared to the high-education group. Low education was also associated with increased glycated haemoglobin levels. Psychosocial resources, occupation, and health behaviours fully explained these inverse associations. In the MR analysis of 210 SNPs (R2 = 0.0161), the odds ratio of having T2DM per standard deviation-decreasing years (4.2 years) of schooling was 1.33 (1.01-1.75; IVW), 1.23 (0.37-4.17; MR-Egger), 1.56 (1.09-2.27; WM), and 2.94 (0.98-9.09; WMBE). However, applying Steiger filtering attenuated most MR results towards the null. CONCLUSIONS: Our inconsistent findings between cohort and genetic evidence did not support the causality between education and T2DM.
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