Effect of weight on depression using multiple genetic instruments

Area of Science:

• Public Health
• Genetics
• Psychiatry

Background:

• Rising rates of overweight/obesity and depression globally present a significant public health challenge.
• Understanding the causal relationship between body weight and mental health is crucial for effective interventions.

Purpose of the Study:

• To investigate the causal effect of body mass index (BMI) on depression symptoms in a Finnish population.
• To differentiate potential causal links between BMI and depression in males and females.

Main Methods:

• Utilized data from the Cardiovascular Risk in Young Finns Study (N=1,523).
• Employed linear regression to assess the association between BMI and depression symptoms (Beck's Depression Inventory).
• Applied Mendelian randomization (MR) using genetic markers (SNPs) and polygenic risk scores (PGSs) as instrumental variables for BMI.

Main Results:

• Linear regression showed higher BMI associated with increased depression symptoms in both females and males.
• Mendelian randomization results indicated a causal link between higher BMI and depression symptoms only in females (p=0.007).
• No significant causal link was found between BMI and depression symptoms in males (p=0.520) via MR.

Conclusions:

• The causal effect of BMI on depression symptoms appears to be sex-specific, primarily affecting females.
• Mendelian randomization provides stronger evidence for a causal link than traditional regression, especially with robust genetic instruments.
• Future research should consider sex differences and utilize powerful genetic instruments to clarify the BMI-depression relationship.