Large differences in adiponectin levels have no clear effect on multiple sclerosis risk: A Mendelian randomization...

Area of Science:

• Neuroimmunology
• Metabolic Health
• Genetic Epidemiology

Background:

• Mendelian randomization (MR) studies indicate a link between higher body mass index (BMI) and increased multiple sclerosis (MS) risk.
• Adiponectin, an adipokine, is a potential mediator connecting body mass to MS pathogenesis.

Purpose of the Study:

• To investigate the causal effect of genetically elevated adiponectin levels on the risk of developing MS.
• To determine if adiponectin plays a role in the established association between BMI and MS.

Main Methods:

• Utilized a Mendelian randomization (MR) approach employing genome-wide significant single nucleotide polymorphisms (SNPs) associated with adiponectin.
• Applied sensitivity analyses, including MR-Egger regression, to assess potential biases like pleiotropy and reverse causation.

Main Results:

• MR analyses revealed no significant association between genetically determined higher adiponectin levels and MS risk (OR = 0.93; 95% CI = 0.66-1.33; p = 0.61).
• Further genetic analysis indicated that variation in the adiponectin gene does not impact MS risk.
• Sensitivity analyses confirmed the robustness of the findings, ruling out significant pleiotropic effects.

Conclusions:

• Lifelong genetically influenced adiponectin levels do not have a discernible effect on multiple sclerosis risk in humans.
• The underlying biological mechanisms linking body mass and MS risk require further investigation beyond adiponectin.