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Genes Brain Behav. 2012 Nov;11(8):942-8. doi: 10.1111/j.1601-183X.2012.00846.x. Epub 2012 Oct 1.

Body mass index and depressive symptoms: instrumental-variables regression with genetic risk score.

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Institute of Behavioural Sciences, University of Helsinki, Helsinki, Finland.
National Institute for Health and Welfare, Helsinki, Finland.
Department of Epidemiology and Public Health, University College London, London, UK.
Department of Psychology, Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.
Helsinki Collegium for Advanced Studies, University of Helsinki, Helsinki, Finland.
Department of Clinical Chemistry, Centre for Laboratory Medicine, Tampere University Hospital, Tampere, Finland.
Medical School, University of Tampere, Tampere, Finland.
Department of Clinical Physiology, Tampere University Hospital, Tampere, Finland.
Department of Medicine, Turku University Hospital.
Department of Clinical Physiology, Turku University Hospital and Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.


The causal role of obesity in the development of depression remains uncertain. We applied instrumental-variables regression (Mendelian randomization) to examine the association of adolescent and adult body mass index (BMI) with adult depressive symptoms. Participants were from the Young Finns prospective cohort study (n = 1731 persons, 2844 person-observations), with repeated measurements of BMI and depressive symptoms (modified Beck's Depression Inventory). Genetic risk score of 31 single nucleotide polymorphisms previously identified as robust genetic markers of body weight was used as a proxy for variation in BMI. In standard linear regression analysis, higher adult depressive symptoms were predicted by higher adolescent BMI (B = 0.33, CI = 0.06-0.60, P = 0.017) and adult BMI (B = 0.47, CI = 0.32-0.63, P < 0.001). These associations were replicated in instrumental-variables analysis with genetic risk score as instrument (B = 1.96, CI = 0.03-3.90, P = 0.047 for adolescent BMI; B = 1.08, CI = 0.11-2.04, P = 0.030 for adult BMI). The association for adolescent BMI was significantly stronger in the instrumented analysis compared to standard regression (P = 0.04). These findings provide additional evidence to support a causal role for high BMI in increasing symptoms of depression. However, the present analysis also demonstrates potential limitations of applying Mendelian randomization when using complex phenotypes.


Adolescence; Mendelian randomization; adulthood; body mass index; depression; genetic risk score; instrumental variables; obesity

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