Are blood lipids risk factors for fracture? Integrative evidence from instrumental variable causal inference and mediation analysis using genetic data

Bone ◽  
2020 ◽  
Vol 131 ◽  
pp. 115174 ◽  
Author(s):  
Haimiao Chen ◽  
Zhonghe Shao ◽  
Yixin Gao ◽  
Xinghao Yu ◽  
Shuiping Huang ◽  
...  
Keyword(s):  
Risk Factors ◽  
Causal Inference ◽  
Mediation Analysis ◽  
Instrumental Variable ◽  
Blood Lipids ◽  
Genetic Data

scholarly journals Mendelian randomisation for mediation analysis: current methods and challenges for implementation

2021 ◽  
Author(s):  
Alice R. Carter ◽  
Eleanor Sanderson ◽  
Gemma Hammerton ◽  
Rebecca C. Richmond ◽  
George Davey Smith ◽  
...  
Keyword(s):  
Measurement Error ◽  
Causal Inference ◽  
Mediation Analysis ◽  
Instrumental Variable ◽  
Real Data ◽  
Mendelian Randomisation ◽  
Differential Measurement ◽  
Individual Level ◽  
Differential Measurement Error ◽  
Summary Data

AbstractMediation 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 difficulties, including bias due to confounding between an exposure, mediator and outcome and measurement error. Mendelian randomisation (MR) can be used to improve causal inference for mediation analysis. We describe two approaches that can be used for estimating mediation analysis with MR: multivariable MR (MVMR) and two-step MR. We outline the approaches and provide code to demonstrate how they can be used in mediation analysis. We review issues that can affect analyses, including confounding, measurement error, weak instrument bias, interactions between exposures and mediators and analysis of multiple mediators. Description of the methods is supplemented by simulated and real data examples. Although MR relies on large sample sizes and strong assumptions, such as having strong instruments and no horizontally pleiotropic pathways, our simulations demonstrate that these methods are unaffected by confounders of the exposure or mediator and the outcome and non-differential measurement error of the exposure or mediator. Both MVMR and two-step MR can be implemented in both individual-level MR and summary data MR. MR mediation methods require different assumptions to be made, compared with non-instrumental variable mediation methods. Where these assumptions are more plausible, MR can be used to improve causal inference in mediation analysis.

Haematocrit: Relationships with Blood Lipids, Blood Pressure and other Cardiovascular Risk Factors

1994 ◽  
Vol 72 (01) ◽  
pp. 058-064 ◽  
Author(s):  
Goya Wannamethee ◽  
A Gerald Shaper
Keyword(s):  
Physical Activity ◽  
Risk Factors ◽  
Blood Pressure ◽  
Body Mass Index ◽  
Cardiovascular Risk ◽  
Cardiovascular Risk Factors ◽  
Alcohol Intake ◽  
Blood Lipids ◽  
The Other ◽  
The Relationship

SummaryThe relationship between haematocrit and cardiovascular risk factors, particularly blood pressure and blood lipids, has been examined in detail in a large prospective study of 7735 middle-aged men drawn from general practices in 24 British towns. The analyses are restricted to the 5494 men free of any evidence of ischaemic heart disease at screening.Smoking, body mass index, physical activity, alcohol intake and lung function (FEV1) were factors strongly associated with haematocrit levels independent of each other. Age showed a significant but small independent association with haematocrit. Non-manual workers had slightly higher haematocrit levels than manual workers; this difference increased considerably and became significant after adjustment for the other risk factors. Diabetics showed significantly lower levels of haematocrit than non-diabetics. In the univariate analysis, haematocrit was significantly associated with total serum protein (r = 0*18), cholesterol (r = 0.16), triglyceride (r = 0.15), diastolic blood pressure (r = 0.17) and heart rate (r = 0.14); all at p <0.0001. A weaker but significant association was seen with systolic blood pressure (r = 0.09, p <0.001). These relationships remained significant even after adjustment for age, smoking, body mass index, physical activity, alcohol intake, lung function, presence of diabetes, social class and for each of the other biological variables; the relationship with systolic blood pressure was considerably weakened. No association was seen with blood glucose and HDL-cholesterol. This study has shown significant associations between several lifestyle characteristics and the haematocrit and supports the findings of a significant relationship between the haematocrit and blood lipids and blood pressure. It emphasises the role of the haematocrit in assessing the risk of ischaemic heart disease and stroke in individuals, and the need to take haematocrit levels into account in determining the importance of other cardiovascular risk factors.

Precarious employment, psychosocial risk factors and poor mental health: A cross-sectional mediation analysis

2021 ◽  
Vol 143 ◽  
pp. 105439
Author(s):  
Fabrizio Méndez Rivero ◽  
Eva Padrosa ◽  
Mireia Utzet ◽  
Joan Benach ◽  
Mireia Julià
Keyword(s):  
Mental Health ◽  
Risk Factors ◽  
Mediation Analysis ◽  
Poor Mental Health ◽  
Psychosocial Risk Factors ◽  
Psychosocial Risk ◽  
Cross Sectional ◽  
Precarious Employment

scholarly journals Mendelian randomisation for mediation analysis: current methods and challenges for implementation

2019 ◽  
Author(s):  
Alice R Carter ◽  
Eleanor Sanderson ◽  
Gemma Hammerton ◽  
Rebecca C Richmond ◽  
George Davey Smith ◽  
...  
Keyword(s):  
Measurement Error ◽  
Causal Inference ◽  
Mediation Analysis ◽  
Real Data ◽  
Mendelian Randomisation ◽  
Reverse Causality ◽  
Differential Measurement ◽  
Individual Level ◽  
Differential Measurement Error ◽  
Summary Data

AbstractMediation analysis seeks to explain the pathway(s) through which an exposure affects an outcome. Mediation analysis experiences a number of methodological difficulties, including bias due to confounding and measurement error. Mendelian randomisation (MR) can be used to improve causal inference for mediation analysis. We describe two approaches that can be used for estimating mediation analysis with MR: multivariable Mendelian randomisation (MVMR) and two-step Mendelian randomisation. We outline the approaches and provide code to demonstrate how they can be used in mediation analysis. We review issues that can affect analyses, including confounding, measurement error, weak instrument bias, and analysis of multiple mediators. Description of the methods is supplemented by simulated and real data examples. Although Mendelian randomisation relies on large sample sizes and strong assumptions, such as having strong instruments and no horizontally pleiotropic pathways, our examples demonstrate that it is unlikely to be affected by confounders of the exposure or mediator and the outcome, reverse causality and non-differential measurement error of the exposure or mediator. Both MVMR and two-step MR can be implemented in both individual-level MR and summary data MR, and can improve causal inference in mediation analysis.

Abstract 40: Empirical Comparison of Approaches to Mediation Analyses in Nutrition Research With Applications to the Quality Cohort

Circulation ◽  
2020 ◽  
Vol 141 (Suppl_1) ◽  
Author(s):  
Karine Suissa ◽  
Andrea Benedetti ◽  
Melanie Henderson ◽  
Katherine Gray-Donald ◽  
Gilles Paradis
Keyword(s):  
Lipid Profile ◽  
Direct Effect ◽  
Fat Mass ◽  
Mediation Analysis ◽  
Blood Lipids ◽  
Glycemic Load ◽  
Small Sample ◽  
Conventional Approach ◽  
Nutrition Research ◽  
Nutritional Studies

Background: Adiposity may mediate the effect of dietary glycemic load (GL) on lipid profile in children as studies have shown an association between dietary GL and adiposity and between adiposity and lipid profiles. While several approaches for conducting mediation analysis have been proposed, given the strict assumptions and restrictions for each method, it is not clear which method is ideal in nutrition research. Our objective was to compare the conventional approach and the causal approach using marginal structural models (MSM) with inverse probability weights (IPW) to examine adiposity as a mediator in the association between baseline dietary GL and lipid profile after 2 years. Methods: The QUALITY cohort included 630 children, 8-10 years at recruitment with at least one obese parent followed-up 2 years later. Three separate 24-hour dietary recalls were administered by a dietitian at baseline. Child and parent characteristics were obtained through direct measurement (blood lipids, anthropometrics) or questionnaires (socio-economic characteristics). Indicators of adiposity, including BMI z-score and percent fat mass, were the mediators of interest. A conventional approach of statistical adjustment for the mediator was used. As well, we used MSM to estimate the controlled direct effect (CDE) between GL and blood lipids 2 years later not mediated by adiposity. The MSM models were constructed using IPW truncated at 5-95 percentile. Results: Mean age of children at baseline was 9.6 years and 33% were overweight or obese. Both mediation analysis methods revealed that most of the effect of GL on blood lipids was mediated by adiposity. Results obtained from both methods differed; while the MSM with IPW did not show evidence of a direct effect of GL on TG not via percent fat mass (TG: β=0.06, 95%CI=-0.01, 0.12; HDL: β=-0.01, 95%CI=-0.04, 0.03), the conventional method did (TG: β=0.03, 95%CI=0.003, 0.06; HDL: β=-0.02, 95%CI=-0.03, -0.001). Conclusion: In conclusion, our results suggest that adiposity contributes substantially to the association between GL and blood lipids after 2 years. MSM with IPW may not be appropriate in nutritional studies with small sample sizes.

scholarly journals Is association of preterm birth with cognitive-neurophysiological impairments and ADHD symptoms consistent with a causal inference or due to familial confounds?

2019 ◽  
Vol 50 (8) ◽  
pp. 1278-1284
Author(s):  
Sarah-Naomi James ◽  
Anna-Sophie Rommel ◽  
Fruhling Rijsdijk ◽  
Giorgia Michelini ◽  
Gráinne McLoughlin ◽  
...  
Keyword(s):  
Risk Factors ◽  
Working Memory ◽  
Preterm Birth ◽  
Causal Inference ◽  
Executive Control ◽  
Error Processing ◽  
Adhd Symptoms ◽  
Family Level ◽  
Per Se ◽  
Preterm Born

AbstractBackgroundPreterm birth is associated with an increased risk for cognitive-neurophysiological impairments and attention-deficit/hyperactivity disorder (ADHD). Whether the associations are due to the preterm birth insult per se, or due to other risk factors that characterise families with preterm-born children, is largely unknown.MethodsWe employed a within-sibling comparison design, using cognitive-performance and event-related potential (ERP) measures from 104 preterm-born adolescents and 104 of their term-born siblings. Analyses focused on ADHD symptoms and cognitive and ERP measures from a cued continuous performance test, an arrow flanker task and a reaction time task.ResultsWithin-sibling analyses showed that preterm birth was significantly associated with increased ADHD symptoms (β = 0.32, p = 0.01, 95% CI 0.05 to 0.58) and specific cognitive-ERP impairments, such as IQ (β = −0.20, p = 0.02, 95% CI −0.40 to −0.01), preparation-vigilance measures and measures of error processing (ranging from β = 0.71, −0.35). There was a negligible within-sibling association between preterm birth with executive control measures of inhibition (NoGo-P3, β = −0.07, p = 0.45, 95% CI −0.33 to 0.15) or verbal working memory (digit span backward, β = −0.05, p = 0.63, 95% CI −0.30 to 0.18).ConclusionsOur results suggest that the relationship between preterm birth with ADHD symptoms and specific cognitive-neurophysiological impairments (IQ, preparation-vigilance and error processing) is independent of family-level risk and consistent with a causal inference. In contrast, our results suggest that previously observed associations between preterm birth with executive control processes of inhibition and working memory are instead linked to background characteristics of families with a preterm-born child rather than preterm birth insult per se. These findings suggest that interventions need to target both preterm-birth specific and family-level risk factors.

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