‘Mendelian randomization’: an approach for exploring causal relations in epidemiology

Gupta, Vipin; Walia, Gagandeep Kaur; Sachdeva, M.P.

doi:10.1016/j.puhe.2016.12.033

Cited by 77 publications

(53 citation statements)

References 65 publications

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“…Because of potential confounders, together with reverse causation, the OLS regression coefficients may be biased 39 . Therefore, the analysis is extended with the IV method, that is, one‐sample MR, in which the GRS for years of education was used as an instrument for educational attainment 25,40 …”

Section: Methodsmentioning

confidence: 99%

Education leads to a more physically active lifestyle: Evidence based on Mendelian randomization

Kari

Viinikainen

Böckerman

et al. 2020

Scandinavian Med Sci Sports

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Physical inactivity is a major health risk worldwide. Observational studies suggest that higher education is positively related to physical activity, but it is not clear whether this relationship constitutes a causal effect. Using participants (N = 1651) drawn from the Cardiovascular Risk in Young Finns Study linked to nationwide administrative data from Statistics Finland, this study examined whether educational attainment, measured by years of education, is related to adulthood physical activity in terms of overall physical activity, weekly hours of intensive activity, total steps per day, and aerobic steps per day. We employed ordinary least squares (OLS) models and extended the analysis using an instrumental variables approach (Mendelian randomization, MR) with a genetic risk score as an instrument for years of education. Based on the MR results, it was found that years of education is positively related to physical activity. On average, one additional year of education leads to a 0.62‐unit higher overall physical activity (P < .01), 0.26 more hours of weekly intensive activity (P < .05), 560 more steps per day (P < .10), and 390 more aerobic steps per day (P < .09). The findings indicate that education may be a factor leading to higher leisure‐time physical activity and thus promoting global health.

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Section: Methodsmentioning

confidence: 99%

Education leads to a more physically active lifestyle: Evidence based on Mendelian randomization

Kari

Viinikainen

Böckerman

et al. 2020

Scandinavian Med Sci Sports

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“…The association of this instrument with the exposure is not affected by any confounding factors (because the genetic sequence is randomly assigned during conception), and it is associated with the outcome only via its effects on the exposure. (6) MR has been successful in inferring causality for several clinically important traits (7) and for elucidating the complex etiology of common disease. (8) In this study, we used MR on a genome-metabolome-wide scale.…”

Section: Identification Of Metabolites That Are Causally Associated Withmentioning

confidence: 99%

Metabolomic Pathways to Osteoporosis in Middle-Aged Women: A Genome-Metabolome-Wide Mendelian Randomization Study

Moayyeri

Cheung

Tan

et al. 2017

Journal of Bone and Mineral Research

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The metabolic state of the body can be a major determinant of bone health. We used a Mendelian randomization approach to identify metabolites causally associated with bone mass to better understand the biological mechanisms of osteoporosis. We tested bone phenotypes (femoral neck, total hip, and lumbar spine bone mineral density [BMD]) for association with 280 fasting blood metabolites in 6055 women from TwinsUK cohort with genomewide genotyping scans. Causal associations between metabolites and bone phenotypes were further assessed in a bidirectional Mendelian randomization study using genetic markers/scores as instrumental variables. Significant associations were replicated in 624 participants from the Hong Kong Osteoporosis Study (HKOS). Fifteen metabolites showed direct associations with bone phenotypes after adjusting for covariates and multiple testing. Using genetic instruments, four of these metabolites were found to be causally associated with hip or spine BMD. These included androsterone sulfate, epiandrosterone sulfate, 5alpha‐androstan‐3beta17beta‐diol disulfate (encoded by CYP3A5), and 4‐androsten‐3beta17beta‐diol disulfate (encoded by SULT2A1). In the HKOS population, all four metabolites showed significant associations with hip and spine BMD in the expected directions. No causal reverse association between BMD and any of the metabolites were found. In the first metabolome‐genomewide Mendelian randomization study of human bone mineral density, we identified four novel biomarkers causally associated with BMD. Our findings reveal novel biological pathways involved in the pathogenesis of osteoporosis. © 2017 American Society for Bone and Mineral Research.

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“…This method uses genetic instruments to estimate causal effects (Tyrrell et al, 2016;Böckerman et al, 2017;Gupta et al, 2017). The method exploits Mendel's law of independent assortment according to which trait is inherited independently from other traits at conception.…”

Section: Mendelian Randomizationmentioning

confidence: 99%

“…The current study examines the relationship between education and BMI using Mendelian randomization, which is based on the random assignment of genotypes at conception (Tyrrell et al, 2016;Gupta et al, 2017;Davey Smith et al, 2017). This randomization by nature enables the use of a genetic score as an instrument for education and to detect a causal relationship between education and BMI.…”

Section: Introductionmentioning

confidence: 99%

Does higher education protect against obesity? Evidence using Mendelian randomization

Böckerman

Viinikainen

Pulkki-Råbäck

et al. 2017

Preventive Medicine

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Objectives. The aim of this explorative study was to examine the effect of education on obesity using Mendelian randomization.Methods. Participants (N=2011) were from the on-going nationally representative Young Finns Study (YFS) that began in 1980 when six cohorts (aged 30, 33, 36, 39, 42 and Conclusion.The findings indicate that education could be a protective factor against obesity in advanced countries.Keywords: Education; schooling; obesity; body weight; BMI; waist-hip ratio Word count, abstract: 239 Word count, article: 3471 HighlightsEducation is a potential determinant of obesity.We use genetic information to account for confounders.The IV estimates suggest a negative causal effect of education on BMI.The effect of education on waist-to-hip ratio is not statistically significant.

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‘Mendelian randomization’: an approach for exploring causal relations in epidemiology

Cited by 77 publications

References 65 publications

Education leads to a more physically active lifestyle: Evidence based on Mendelian randomization

Education leads to a more physically active lifestyle: Evidence based on Mendelian randomization

Metabolomic Pathways to Osteoporosis in Middle-Aged Women: A Genome-Metabolome-Wide Mendelian Randomization Study

Does higher education protect against obesity? Evidence using Mendelian randomization

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