McGill University

Author Of 2 Presentations

Epidemiology Oral Presentation

FC04.05 - Understanding the relative contributions of obesity, vitamin D, leptin and adiponectin to MS risk: a Mendelian randomization mediation analysis

Speakers
Presentation Number
FC04.05
Presentation Topic
Epidemiology
Lecture Time
13:48 - 14:00

Abstract

Background

Obesity is increasingly recognized as a risk for multiple sclerosis (MS). While the underlying mechanisms remain undetermined, reduced vitamin D bioavailability and altered levels of the immunomodulatory cytokines adiponectin and leptin have been proposed.

Objectives

To determine the roles of vitamin D, adiponectin and leptin levels in explaining the effect of obesity on MS, using a Mendelian randomization (MR) mediation framework.

Methods

Independent genetic estimates for body mass index (BMI), 25-hydroxyvitamin D (25OHD), adiponectin and leptin levels were obtained from from large-scale genome-wide association studies and the UK Biobank, totalling over 800,000 participants. The effect on MS was measured using summary genetic data on 14,802 MS cases and 26,703 controls from the International MS Genetics Consortium (IMSGC). To avoid bias from population stratification, all participants were of European ancestry. We estimated the odds of MS for each of the exposures, and the proportion of the effect of BMI explained by potential mediators significantly associated with MS, using the product of coefficients method in a two-step MR framework.

Results

Each standard deviation (SD) increase in BMI was associated with a 40% increase in the odds of MS (95% CI 1.16 to 1.67, P=3.1x10-4). Similarly, a SD increase in standardized log transformed 25OHD levels reduced the odds of MS by 28% (95% CI 0.60-0.87, P=6.2x10-4). In contrast, we observed no notable effect of adiponectin (OR=1.05, 95% CI 0.74-1.49, P=0.78) or leptin (OR=1.18, 95% CI 0.59-2.36, P=0.64) on the odds of MS. In MR mediation analysis, we estimate that the reduction in 25OHD levels only explains 5.4% of the effect of increased BMI on the risk of MS (95% CI 0.4% to 30.5%). Sensitivity analyses showed that these estimates were robust to potential bias from pleiotropy.

Conclusions

This study found that only a minority of the increased risk of MS conferred by obesity is mediated by lowered vitamin D levels, while leptin and adiponectin had no measurable effect. This suggests that vitamin D supplementation would only modestly reverse the effect of obesity on MS, the majority of which remains unexplained.

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Invited Presentations Invited Abstracts

PS08.02 - Mendelian Randomization in MS

Speakers
Authors
Presentation Number
PS08.02
Presentation Topic
Invited Presentations
Lecture Time
13:00 - 13:15

Abstract

Abstract

Traditional epidemiological observational studies in multiple sclerosis (MS) can be biased by confounding, which occurs when there is a common cause of the exposure and the outcome. Further, given the insidious onset of the disease, measuring the exposure prior to the date of diagnosis, does not guarantee against reverse causation, where the outcome directly influences the exposure. An established method to overcome these issues is Mendelian randomization (MR).

In this invited talk, I will discuss recent advances in MR and how they can improve causal inference in the field of MS. Specifically, I will draw upon studies from our group and others that have used MR to shed light on factors that likely influence predisposion to MS. I will discuss new and emerging methods in the field of MR and focus upon proper reporting of MS studies to ensure that they can be interpreted and applied by clinicians.

I will review recent studies in the field of MS, which use GWAS and emerging sequencing studies to better understand the causal pathways that influence this disease.

In this invited talk, I will discuss results from recent MR studies and provide practical tips on the implementation of such studies in the field of MS.

MR studies can make important contributions to our understanding of the causes of MS and in some cases can help to prioritize randomized controlled trials, as well as provide causal inference information when such trials are not impossible of unethical. Taken together, the findings from recent MR studies in MS have helped to disentangle multiple controversies in the field and help to provide orthogonal lines of evidence to test long-standing hypothesis in the field.

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Presenter Of 1 Presentation

Invited Presentations Invited Abstracts

PS08.02 - Mendelian Randomization in MS

Speakers
Authors
Presentation Number
PS08.02
Presentation Topic
Invited Presentations
Lecture Time
13:00 - 13:15

Abstract

Abstract

Traditional epidemiological observational studies in multiple sclerosis (MS) can be biased by confounding, which occurs when there is a common cause of the exposure and the outcome. Further, given the insidious onset of the disease, measuring the exposure prior to the date of diagnosis, does not guarantee against reverse causation, where the outcome directly influences the exposure. An established method to overcome these issues is Mendelian randomization (MR).

In this invited talk, I will discuss recent advances in MR and how they can improve causal inference in the field of MS. Specifically, I will draw upon studies from our group and others that have used MR to shed light on factors that likely influence predisposion to MS. I will discuss new and emerging methods in the field of MR and focus upon proper reporting of MS studies to ensure that they can be interpreted and applied by clinicians.

I will review recent studies in the field of MS, which use GWAS and emerging sequencing studies to better understand the causal pathways that influence this disease.

In this invited talk, I will discuss results from recent MR studies and provide practical tips on the implementation of such studies in the field of MS.

MR studies can make important contributions to our understanding of the causes of MS and in some cases can help to prioritize randomized controlled trials, as well as provide causal inference information when such trials are not impossible of unethical. Taken together, the findings from recent MR studies in MS have helped to disentangle multiple controversies in the field and help to provide orthogonal lines of evidence to test long-standing hypothesis in the field.

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Invited Speaker Of 1 Presentation

Invited Presentations Invited Abstracts

PS08.02 - Mendelian Randomization in MS

Speakers
Authors
Presentation Number
PS08.02
Presentation Topic
Invited Presentations
Lecture Time
13:00 - 13:15

Abstract

Abstract

Traditional epidemiological observational studies in multiple sclerosis (MS) can be biased by confounding, which occurs when there is a common cause of the exposure and the outcome. Further, given the insidious onset of the disease, measuring the exposure prior to the date of diagnosis, does not guarantee against reverse causation, where the outcome directly influences the exposure. An established method to overcome these issues is Mendelian randomization (MR).

In this invited talk, I will discuss recent advances in MR and how they can improve causal inference in the field of MS. Specifically, I will draw upon studies from our group and others that have used MR to shed light on factors that likely influence predisposion to MS. I will discuss new and emerging methods in the field of MR and focus upon proper reporting of MS studies to ensure that they can be interpreted and applied by clinicians.

I will review recent studies in the field of MS, which use GWAS and emerging sequencing studies to better understand the causal pathways that influence this disease.

In this invited talk, I will discuss results from recent MR studies and provide practical tips on the implementation of such studies in the field of MS.

MR studies can make important contributions to our understanding of the causes of MS and in some cases can help to prioritize randomized controlled trials, as well as provide causal inference information when such trials are not impossible of unethical. Taken together, the findings from recent MR studies in MS have helped to disentangle multiple controversies in the field and help to provide orthogonal lines of evidence to test long-standing hypothesis in the field.

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