Body mass index and psychiatric disorders: a Mendelian randomization study.
Obesity is a highly prevalent risk factor for cardiometabolic diseases. Observational studies suggest that obesity is associated with psychiatric traits, but causal inference from such studies has several limitations. We used two-sample Mendelian randomization methods (inverse variance weighting, weighted median and MR-Egger regression) to evaluate the association of body mass index (BMI) with three psychiatric traits using data from the Genetic Investigation of Anthropometric Traits and Psychiatric Genomics consortia. Causal odds ratio estimates per 1-standard deviation increment in BMI ranged from 0.88 (95% CI: 0.62; 1.25) to 1.23 (95% CI: 0.65; 2.31) for bipolar disorder; 0.93 (0.78; 1.11) to 1.41 (0.87; 2.27) for schizophrenia; and 1.15 (95% CI: 0.92; 1.44) to 1.40 (95% CI: 1.03; 1.90) for major depressive disorder. Analyses removing potentially influential SNPs suggested that the effect estimates for depression might be underestimated. Our findings do not support the notion that higher BMI increases risk of bipolar disorder and schizophrenia. Although the point estimates for depression were consistent in all sensitivity analyses, the overall statistical evidence was weak. However, the fact that SNP-depression associations were estimated in relatively small samples reduced power to detect causal effects. This should be re-addressed when SNP-depression associations from larger studies become available.
Postgraduate Program in Epidemiology, Federal University of Pelotas, Pelotas, Brazil.
Fernando Pires
FP
Hartwig
MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.|MRC Biostatistics Unit, University of Cambridge, Cambridge, UK.
Jack
J
Bowden
Postgraduate Program in Epidemiology, Federal University of Pelotas, Pelotas, Brazil.
Christian
C
Loret de Mola
Postgraduate Program in Epidemiology, Federal University of Pelotas, Pelotas, Brazil.
Luciana
L
Tovo-Rodrigues
MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
George
G
Davey Smith
Postgraduate Program in Epidemiology, Federal University of Pelotas, Pelotas, Brazil.
Bernardo Lessa
BL
Horta
D001714:Bipolar Disorder / Q000235:genetics*; D015992:Body Mass Index; D003865:Major Depressive Disorder / Q000235:genetics*; D055106:Genome-Wide Association Study; D006801:Humans; D057182:Mendelian Randomization Analysis / Q000379:methods*; D009765:Obesity / Q000235:genetics / Q000523:psychology*; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012559:Schizophrenia / Q000235:genetics*