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Obesity has been associated with elevated risk of depression. If this association is causal, the increasing obesity prevalence might lead to worsening population mental health, but the strength of the causal effect has not been systematically evaluated.



Meta-analysis of 8 Mendelian randomization studies indicated an OR = 1.33 higher depression risk associated with obesity (95% confidence interval 1.19, 1.48). Between 15% and 20% of the participants of HSE and NHIS reported at least moderate psychological distress. The increase of obesity prevalence from the 1990s–2010s in HSE and NHIS would have led to a 0.6 percentage-point increase in population psychological distress.

Obesity as a causal risk factor for depression: Systematic review and meta-analysis of Mendelian Randomization studies and implications for population mental health

Markus Jokela, Michael Laakasuo

The current study provides a systematic review and meta-analysis of studies examining associations between body mass index and depression using Mendelian randomization with multiple genetic variants as instruments for body mass index. We used this estimate to calculate the expected changes in prevalence of population psychological distress from the 1990s–2010s, which were compared with the empirically observed trends in psychological distress in the Health Survey for England (HSE) and U.S. National Health Interview Surveys (NHIS).


Sample Size

8 studies included.
Of the 23 studies that were retrieved for detailed inspection for eligibility, 15 were excluded because of the following reasons (Fig. 1): Two studies reported associations separately for depression (Walter et al., 2015a) and phobic anxiety (Walter et al., 2015b) from the same Nurses' Health Study, so we excluded the study of anxiety (Walter et al., 2015b) so as not to include the same data twice, and because we were primarily interested in depression as the outcome. One study (Samaan et al., 2015) was excluded because it only reported associations between the BMI genetic risk score and depression (OR = 1.01 per obesity-associated allele of a 21-SNP risk score, 95%CI = 0.99, 1.02) but not the gene–instrumented association between BMI and depression. Two studies from the UK Biobank cohort study were excluded: The first (Millard et al., 2019) reported associations between BMI and neuroticism-type personality characteristics separately by each questionnaire item (e.g., being nervous, a worrier, tense, and ‘suffering from nerves'). High neuroticism is related to depression (Hakulinen et al., 2015), but the study was excluded because of the use of single personality items as the outcomes. The second study (Wootton et al., 2018) examined how BMI was related to five domains of life satisfaction (work, health, finances, friends, and family) and single-item scale of happiness. This study was also excluded because of the use of single-item questions. Two studies (Kivimäki et al., 2011b; Lawlor et al., 2011) used only single genes (FTO or MC4R) as instruments for BMI, which limits the validity of the instrument, and these two studies were therefore excluded.


Mendelian randomization studies suggest that obesity is a causal risk factor for elevated risk of depression. The increasing obesity rates may have modestly increased the prevalence of depressive symptoms in the general population. Mendelian randomization relies on methodological assumptions that may not always hold, so other quasi-experimental methods are needed to confirm the current conclusions.

In sum, obesity seems to be a causal risk factor for depression, increasing its odds by 33%. Between 15% and 20% of the general population are estimated to suffer from at least moderate psychological distress. The doubling of obesity prevalence from the 1990s–2010s would have increased this prevalence by one-half percentage points.


obesity, depression

Key Words

Jokela, Markus, and Michael Laakasuo. “Obesity as a Causal Risk Factor for Depression: Systematic Review and Meta-Analysis of Mendelian Randomization Studies and Implications for Population Mental Health.” Journal of Psychiatric Research, vol. 163, July 2023, pp. 86–92. (Crossref),


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