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Article
Open AccessSerum vitamin D, blood pressure and hypertension risk in the HUNT study using observational and Mendelian randomization approaches
Limited studies have triangulated the relationship between serum 25-hydroxyvitamin D [25(OH)D] levels and systolic blood pressure (SBP), diastolic blood pressure (DBP) or hypertension risk utilizing both obser...
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Article
Open AccessMammographic density mediates the protective effect of early-life body size on breast cancer risk
The unexplained protective effect of childhood adiposity on breast cancer risk may be mediated via mammographic density (MD). Here, we investigate a complex relationship between adiposity in childhood and adul...
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Article
Open AccessMethodological approaches, challenges, and opportunities in the application of Mendelian randomisation to lifecourse epidemiology: A systematic literature review
Diseases diagnosed in adulthood may have antecedents throughout (including prenatal) life. Gaining a better understanding of how exposures at different stages in the lifecourse influence health outcomes is key...
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Article
Open AccessChronic inflammation does not mediate the effect of adiposity on grip strength: results from a multivariable Mendelian randomization study
The relationship between adiposity and grip strength (GS) is complex. We investigated whether one pathway through which adiposity affects GS was via chronic inflammation. 367,583 UK Biobank participants had bo...
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Article
Open AccessReappraising the role of instrumental inequalities for mendelian randomization studies in the mega Biobank era
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Article
Open AccessDNA methylation at the suppressor of cytokine signaling 3 (SOCS3) gene influences height in childhood
Human height is strongly influenced by genetics but the contribution of modifiable epigenetic factors is under-explored, particularly in low and middle-income countries (LMIC). We investigate links between blo...
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Article
Open AccessCausal factors in primary open angle glaucoma: a phenome-wide Mendelian randomisation study
Primary open angle glaucoma (POAG) is a chronic, adult-onset optic neuropathy associated with characteristic optic disc and/or visual field changes. With a view to identifying modifiable risk factors for this ...
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Article
Open AccessSeparating the effects of early and later life adiposity on colorectal cancer risk: a Mendelian randomization study
Observational studies have linked childhood obesity with elevated risk of colorectal cancer; however, it is unclear if this association is causal or independent from the effects of obesity in adulthood on colo...
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Article
Open AccessInvestigating causal relations between sleep duration and risks of adverse pregnancy and perinatal outcomes: linear and nonlinear Mendelian randomization analyses
Observational studies have reported maternal short/long sleep duration to be associated with adverse pregnancy and perinatal outcomes. However, it remains unclear whether there are nonlinear causal effects. Ou...
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Article
Open AccessExploring and mitigating potential bias when genetic instrumental variables are associated with multiple non-exposure traits in Mendelian randomization
With the increasing size and number of genome-wide association studies, individual single nucleotide polymorphisms are increasingly found to associate with multiple traits. Many different mechanisms could resu...
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Article
Open AccessApplying Mendelian randomization to appraise causality in relationships between nutrition and cancer
Dietary factors are assumed to play an important role in cancer risk, apparent in consensus recommendations for cancer prevention that promote nutritional changes. However, the evidence in this field has been ...
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Article
Open AccessIdentifying molecular mediators of the relationship between body mass index and endometrial cancer risk: a Mendelian randomization analysis
Endometrial cancer is the most common gynaecological cancer in high-income countries. Elevated body mass index (BMI) is an established modifiable risk factor for this condition and is estimated to confer a lar...
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Article
Open AccessDeciphering how early life adiposity influences breast cancer risk using Mendelian randomization
Studies suggest that adiposity in childhood may reduce the risk of breast cancer in later life. The biological mechanism underlying this effect is unclear but is likely to be independent of body size in adulth...
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Article
Mendelian randomization
Mendelian randomization (MR) is a term that applies to the use of genetic variation to address causal questions about how modifiable exposures influence different outcomes. The principles of MR are based on Me...
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Article
Open AccessRisk factors mediating the effect of body mass index and waist-to-hip ratio on cardiovascular outcomes: Mendelian randomization analysis
Higher body mass index (BMI) and waist-to-hip ratio (WHR) increase the risk of cardiovascular disease, but the extent to which this is mediated by blood pressure, diabetes, lipid traits, and smoking is not ful...
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Article
Open AccessMendelian randomisation for mediation analysis: current methods and challenges for implementation
Mediation analysis seeks to explain the pathway(s) through which an exposure affects an outcome. Traditional, non-instrumental variable methods for mediation analysis experience a number of methodological diff...
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Article
A cross-platform approach identifies genetic regulators of human metabolism and health
In cross-platform analyses of 174 metabolites, we identify 499 associations (P < 4.9 × 10−10) characterized by pleiotropy, allelic heterogeneity, large and nonlinear effects and enrichment for nonsynonymous varia...
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Article
Open AccessAdiposity, metabolites, and colorectal cancer risk: Mendelian randomization study
Higher adiposity increases the risk of colorectal cancer (CRC), but whether this relationship varies by anatomical sub-site or by sex is unclear. Further, the metabolic alterations mediating the effects of adi...
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Article
Open AccessA multivariable Mendelian randomization analysis investigating smoking and alcohol consumption in oral and oropharyngeal cancer
The independent effects of smoking and alcohol in head and neck cancer are not clear, given the strong association between these risk factors. Their apparent synergistic effect reported in previous observation...
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Article
Open AccessAvoiding dynastic, assortative mating, and population stratification biases in Mendelian randomization through within-family analyses
Estimates from Mendelian randomization studies of unrelated individuals can be biased due to uncontrolled confounding from familial effects. Here we describe methods for within-family Mendelian randomization a...
