Abstract.
Background:
Depression and obesity are complex global health problems. Recent studies suggest a
genetic predisposition to obesity might be accentuated in people with depression, but these
analyses are prone to bias. Here, we tested the hypothesis that depression accentuates
genetic susceptibility to obesity and applied ...
Abstract.
Background:
Depression and obesity are complex global health problems. Recent studies suggest a
genetic predisposition to obesity might be accentuated in people with depression, but these
analyses are prone to bias. Here, we tested the hypothesis that depression accentuates
genetic susceptibility to obesity and applied negative control experiments to test whether any
observed interactions were real or driven by confounding and statistical biases.
Methods:
We used data from upto 378,000 Europeans in UK Biobank, a 73 variant Body Mass Index
(BMI) genetic risk score, 2 depression measures (depressive symptoms (DS), major
depression (MD)) and an antidepressant usage variable available. We tested whether a)
depression and b) antidepressant treatment accentuated genetic susceptibility to obesity.
Finally, we performed negative control experiments by sampling individuals at random so
that they had BMI distributions identical to depression cases and controls.
Results:
Depression was associated with an accentuation of an individuals genetic risk of obesity with
evidence of interactions for both DS and MD (Pinteraction=7x10-4 and 7x10-5 respectively).
Antidepressant usage within DS cases accentuated genetic obesity risk (Pinteraction=9x10-4),
but not for MD (Pinteraction=0.13). Negative control experiments suggested that the observed
interactions for MD (empirical-P =0.067) may be driven by statistical biases or confounding
factors but were not possible with the larger DS groups. Antidepressant usage interaction
also appears to be driven by statistical artefacts (empirical-P=0.510 using MD and 0.162
using DS).
Conclusion:
We have highlighted the importance of running negative experiments to confirm putative
interactions in gene-environment studies. We provide some tentative evidence that
depression accentuates an individual’s genetic susceptibility to higher BMI but demonstrated
that the BMI distributions within cases and controls might drive these interactions.
