has received support from industry (Medtronic and Roche Diagnostics) in relation to her biomarker research. et al.Â Burgess Comparison of one-sample and two-sample MR, â¢âCan check this within the population with exposure and outcome (as both in same population), â¢âUse F-statistic and R 2 of genetic instrument-risk factor association as measure of strength, â¢âWeak instrument biases towards the confounded regression analysis result, â¢âCan check this within the population with exposure but need to be careful that the population used for testing genetic instrument-outcome association is the same as that testing instrument-risk factor (e.g. . et al.Â Burgess Such studies exploit what is known as Mendel’s . . Methods and findings. Hemani DC Heron . Yaghootkar Paré et al. From the original papers it can be seen that the instrument for adult BMI is stronger than for the other traits (the respective R 2 for adult BMI, birthweight, child BMI and WHR, are: 0.027, 0.008, 0.020 and 0.013; the R 2 for child BMI is only for the three novel SNPs but, as the authors of the original paper point out, it was calculated on a relatively small sample and needs to be treated with some caution). This two-sample Mendelian randomization study aimed to delve into the effects of genetically predicted adipokine levels on OA.Methods. A gene-based association method for mapping traits using reference transcriptome data. The Mendelian randomization analysis made it possible to examine the effects of lifelong naturally elevated testosterone levels on 469 traits and diseases. We attempted to minimize the risk of bias due to population stratification by restricting to individuals of European ethnicity and adjusting for genetic principal components. Davey Smith However, this is a one-sample MR, as the subgroup âbelongâ to the same study population. Horikoshi Taylor Davey Smith Describe any key additional analyses that would have been important to conduct, such as of sub-phenotypes or interactions, that were not possible because of the summary data. If this overlap is large, then some of the advantages of two-sample over one-sample MR are potentially lost, but the disadvantages of using summary data are maintained. So far, MR studies in this area have focussed solely on Alzheimer’s dementia, with all three reporting no impact of diabetes [4–6]. If this is not the case (as in this paper for the sex-specific cancers), check the original paper publications and/or contact the original authors to see if it is possible to obtain results from the same population (here sex-specific results). 2,3,9 It is notable, for example, that Gao etÂ al. IM Sudlow Smith â¢âIf the same sample is used for GWAS discovery of the instrumental variables (i.e. Figure 1 a and c both illustrate the three key assumptions of IV analyses: i.âthat the IV âZâ (randomization to statins in Figure 1 a and genetic variants related to LDLc in Figure 1 c) is (or is plausibly) causally related to the risk factor (LDLc in all figures); ii.âthat confounding factors for the risk factor-outcome âXâ-âYâ association (here LDLc on CHD in all figures) are not related to the instrumental variable; iii.âthat the instrumental variable âZâ only affects the outcome âYâ (CHD) through its effect on the risk factor âXâ (LDLc). United Nations' Sustainable Development Goals (SDG, 2015) has specified NCDs as one of their important health related targets (Target-3.4) for improving overall wellbeing of human populations (2). . Did you miss the ISSLS Prize webinar or wish to view it again? . If there have been adjustments, ensure that presentation and interpretation of results take this into account. Timpson Thompson Gao Mendelian randomization is the term that has been given to studies that use genetic variants in observational epidemiology to make causal inferences about modiﬁable (non-genetic) risk factors for disease and health-related outcomes [1,3,20]. Davey Smith For two-sample MR to be valid, the two samples have to be from the same underlying population, but for the sex-specific cancers in the paper by Gao etÂ al. Beyond the study findings themselves, this paper is int… Mendelian randomization phenome-wide scan of AMH-associated variants. The extent to which bias towards the null as a possible result of weak instrument bias and adjustment of WHR for BMI (discussed above) is balanced by possible exaggeration of the true effect as a result of not using sex-specific data for the genetic instrument-WHR association in the female cancers, is impossible to tell.
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