306-OR: Gene-Environment Interactions for Type 2 Diabetes in UK Biobank

Background: The body of evidence on gene-environment interaction (GEI) related to type 2 diabetes (T2D) has grown in the recent years. However, most studies on GEI have sought to explain variation within individuals of European ancestry and results among ethnic minority groups are inconclusive. Objective: To investigate any interaction between a gene and an environmental factor in relation to T2D among ethnic minority groups living in Europe and North America. Methods: We systematically searched Medline and EMBASE databases for the published literature in English up to 25th March 2019. The screening, data extraction and quality assessment were performed by reviewers independently. Results: 1068 studies identified through our search, of which nine cohorts of six studies evaluating several different GEIs were included. The mean follow-up time in the included studies ranged from 5 to 25.7 years. Most studies were relatively small scale and few provided replication data. All studies included in the review included ethnic minorities from North America (Native-Americans, African- Americans, and Aboriginal Canadian), none of the studies in Europe assessed GEI in relation to T2D incident in ethnic minorities. The only significant GEI among ethnic minorities was HNF1A rs137853240 and smoking on T2D incident among Native-Canadians (Pinteraction = 0.006). Conclusion: There is a need for more studies on GEI among ethnicities, broadening the spectrum of ethnic minority groups being investigated, performing more discovery using genome-wide approaches, larger sample sizes for these studies by collaborating efforts such as the InterConnect approach, and developing a more standardized method of reporting GEI studies are discussed.

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Gallstone disease, diabetes, calcium, triglycerides, smoking and alcohol consumption and pancreatitis risk: Mendelian randomization study

npj Genomic Medicine ◽

10.1038/s41525-021-00189-6 ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Shuai Yuan ◽

Edward L. Giovannucci ◽

Susanna C. Larsson

Keyword(s):

Type 2 Diabetes ◽

Chronic Pancreatitis ◽

Alcohol Consumption ◽

Mendelian Randomization ◽

Gallstone Disease ◽

Smoking Initiation ◽

Disease Type ◽

Uk Biobank ◽

Increased Risk

AbstractWe conducted a Mendelian randomization study to determine the potential causal associations of gallstone disease, diabetes, serum calcium, triglyceride levels, smoking and alcohol consumption with acute and chronic pancreatitis. Genetic variants associated with the exposures at p < 5 × 10−8 were selected from corresponding genome-wide association studies. Summary-level data for pancreatitis were obtained from the FinnGen consortium and UK Biobank. Univariable and multivariable Mendelian randomization analyses were performed and results from FinnGen and UK Biobank were combined using the fixed-effects meta-analysis method. Genetic predisposition to gallstone disease, type 2 diabetes and smoking initiation was associated with an increased risk of acute pancreatitis. The combined odds ratios (ORs) were 1.74 (95% confidence interval (CI), 1.57, 1.93) for gallstone disease, 1.14 (95% CI, 1.06, 1.21) for type 2 diabetes and 1.56 (95% CI, 1.32, 1.83) for smoking initiation. The association for type 2 diabetes attenuated after adjustment for gallstone disease. Genetic predisposition to gallstone disease and smoking initiation as well as higher genetically predicted serum calcium and triglyceride levels were associated with an increased risk of chronic pancreatitis. The combined ORs of chronic pancreatitis were 1.27 (95% CI, 1.08, 1.50) for gallstone disease, 1.86 (95% CI, 1.43, 2.43) for smoking initiation, 2.20 (95% CI, 1.30, 3.72) for calcium and 1.47 (95% CI, 1.23, 1.76) for triglycerides. This study provides evidence in support that gallstone disease, type 2 diabetes, smoking and elevated calcium and triglyceride levels are causally associated with the risk of acute or chronic pancreatitis.

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Gene–environment interaction in type 2 diabetes

Diabetology International ◽

10.1007/s13340-016-0299-2 ◽

2016 ◽

Vol 8 (1) ◽

pp. 7-13 ◽

Cited By ~ 2

Author(s):

Yoshiaki Kido

Keyword(s):

Type 2 Diabetes ◽

Environment Interaction ◽

Gene Environment Interaction ◽

Gene Environment

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Association of a Healthy Lifestyle With All-Cause and Cause-Specific Mortality Among Individuals With Type 2 Diabetes: A Prospective Study in UK Biobank

10.2337/figshare.16965199 ◽

2021 ◽

Author(s):

Han Han ◽

Yaying Cao ◽

Chengwu Feng ◽

Yan Zheng ◽

Klodian Dhana ◽

...

Keyword(s):

Type 2 Diabetes ◽

Respiratory Disease ◽

Digestive Disease ◽

Diabetes Management ◽

Healthy Lifestyle ◽

Population Attributable Risk ◽

Uk Biobank ◽

All Cause Mortality ◽

Specific Mortality

<a>Objective: </a><a></a><a></a><a></a><a></a><a>To evaluate the association of a healthy lifestyle, involving seven low-risk factors mentioned in diabetes management guidelines (no current smoking, moderate alcohol consumption, regular physical activity, healthy diet, less sedentary behavior, adequate sleep duration, and appropriate social connection), with all-cause and cause-specific mortality among individuals with type 2 diabetes.</a> Research Design and Methods: This study included 13,366 participants with baseline type 2 diabetes from the UK Biobank free of CVD or cancer. Lifestyle information was collected through a baseline questionnaire. <a>Results: During a median follow-up of 11.7 years, 1,561 deaths were documented, with 625 from cancer, 370 from CVD, 115 from respiratory disease, 81 from digestive disease, and 74 from neurodegenerative disease.</a><a> In multivariate-adjusted model, each lifestyle factor was significantly associated with all-cause mortality and hazard ratios (95% CIs) associated with the lifestyle score (scoring 6-7 vs. 0-2 unless specified) were 0.42 (0.34, 0.52) for all-cause mortality, 0.57 (0.41, 0.80) for cancer mortality, 0.35 (0.22, 0.56) for CVD mortality, 0.26 (0.10, 0.63) for respiratory mortality, and 0.28 (0.14, 0.53) for digestive mortality (scoring 5-7 vs. 0-2). In the population-attributable-risk analysis, 27.1% (95% CI: 16.1, 38.0%) death was attributable to a poor lifestyle (scoring 0-5). </a><a>The association between a healthy lifestyle and all-cause mortality was consistent, irrespective of factors reflecting diabetes severity (diabetes duration, glycemic control, diabetes-related microvascular disease, and diabetes medication)</a>. Conclusions: <a></a><a></a>A healthy lifestyle was associated with a lower risk of mortality due to all-cause, CVD, cancer, respiratory disease, and digestive disease among individuals with type 2 diabetes.

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1134-P: Polygenic Risk Score of Type 2 Diabetes as a Predictive Factor for Macrovascular Complications: A Prospective Population-Based UK Biobank Study

Diabetes ◽

10.2337/db21-1134-p ◽

2021 ◽

Vol 70 (Supplement 1) ◽

pp. 1134-P

Author(s):

SANGHYUK JUNG ◽

DOKYOON KIM ◽

MANU SHIVAKUMAR ◽

HONG-HEE WON ◽

JAE-SEUNG YUN

Keyword(s):

Type 2 Diabetes ◽

Risk Score ◽

Predictive Factor ◽

Population Based ◽

Macrovascular Complications ◽

Polygenic Risk Score ◽

Uk Biobank ◽

Polygenic Risk

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Night Shift Work, Genetic Risk, and Type 2 Diabetes in the UK Biobank

Diabetes Care ◽

10.2337/dc17-1933 ◽

2018 ◽

Vol 41 (4) ◽

pp. 762-769 ◽

Cited By ~ 59

Author(s):

Céline Vetter ◽

Hassan S. Dashti ◽

Jacqueline M. Lane ◽

Simon G. Anderson ◽

Eva S. Schernhammer ◽

...

Keyword(s):

Type 2 Diabetes ◽

Shift Work ◽

Genetic Risk ◽

Night Shift ◽

Uk Biobank ◽

Night Shift Work ◽

The Uk

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Abstract 021: C-reactive Protein Partially Mediates The Inverse Association Between Coffee Consumption And Risk Of Type 2 Diabetes: Findings From The UK Biobank And The Rotterdam Studies

Circulation ◽

10.1161/circ.143.suppl_1.021 ◽

2021 ◽

Vol 143 (Suppl_1) ◽

Author(s):

Carolina Ochoa-Rosales ◽

Niels van der Schaft ◽

Kim V Braun ◽

Frederick Ho ◽

Fanny Petermann ◽

...

Keyword(s):

Type 2 Diabetes ◽

Coffee Consumption ◽

Inverse Association ◽

Statistical Regression ◽

Uk Biobank ◽

C Reactive Protein ◽

Coffee Intake ◽

Reactive Protein ◽

The Uk

Background: Coffee intake has been linked to lower type 2 diabetes (T2D) risk. We hypothesized this may be mediated by coffee’s effects on inflammation. Methods: Using participants from the UK Biobank (UKB n=145370) and Rotterdam Study (RS n=7172) cohorts, we studied associations of coffee intake with incident T2D; longitudinally measured insulin resistance (HOMA IR); serum levels of inflammation markers; and the mediating role of inflammation. Statistical regression models were adjusted for sociodemographic, lifestyle and health factors. Results: The median follow up was 7 (UKB) and 9 (RS) years. An increase of one coffee cup/day was associated with 4-6% lower T2D risk (RS HR=0.94 [95% CI 0.90; 0.98]; UKB HR=0.96 [0.94; 0.98]); lower HOMA IR (RS β=-0.017 [-0.024; -0.010]); with lower C reactive protein (CRP) and higher adiponectin (Figure1). Consumers of filtered coffee had the lowest T2D risk (UKB HR=0.88 [0.83; 0.93]). CRP levels mediated 9.6% (UKB) and 3.4% (RS) of the total effect of coffee on T2D (Figure 1). Conclusions: We suggest that coffee’s beneficial effects on lower T2D risk are partially mediated by improvements in systemic inflammation.Figure 1. a CRP and a adiponectin refer to the effect of coffee intake on CRP and adiponectin levels. a CRP RS : β=-0.014 (-0.022; -0.005); UKBB a CRP UKB : β=-0.011 (-0.012; -0.009) and RS a adiponectin : β=0.025 (0.007; 0.042). b CRP and b adiponectin refer to the effect of coffee related levels in CRP and adiponectin on incident T2D, independent of coffee. RS b CRP : HR=1.17 (1.04; 1.31); UKB b CRP : HR=1.45 (1.37; 1.54); and b adiponectin : HR=0.58 (0.32; 0.83). c′ refers to coffee’ effect on T2D going directly or via others mediators. UKB c′ independent of CRP : HR=0.96 (0.94; 0.99); RS c′ independent of CRP : HR=0.94 (0.90; 0.99); and RS c′ independent of CRP+adiponectin : HR=0.90 (0.80; 1.01). Coffee related changes in CRP may partially explain the beneficial link between coffee and T2D, mediating a 3.4% (0.6; 4.8, RS) and 9.6% (5.7; 24.4, UKB). Evidence of mediation was also found for adiponectin.

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