Effect of weight on depression using multiple genetic instruments
Viinikainen, J., Böckerman, P., Willage, B., Elovainio, M., Kari, J. T., Lehtimäki, T., Pehkonen, J., Pitkänen, N., & Raitakari, O. (2024). Effect of weight on depression using multiple genetic instruments. PLoS ONE, 19(2), Article e0297594. https://doi.org/10.1371/journal.pone.0297594
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A striking global health development over the past few decades has been the increasing prevalence of overweight and obesity. At the same time, depression has become increasingly common in almost all high-income countries. We investigated whether body weight, measured by body mass index (BMI), has a causal effect on depression symptoms in Finland. Using data drawn from the Cardiovascular Risk in Young Finns Study (N = 1,523, mean age 41.9, SD 5), we used linear regression to establish the relationship between BMI and depression symptoms measured by 21-item Beck’s Depression Inventory. To identify causal relationships, we used the Mendelian randomization (MR) method with weighted sums of genetic markers (single nucleotide polymorphisms, SNPs) as instruments for BMI. We employ instruments (polygenic risk scores, PGSs) with varying number of SNPs that are associated with BMI to evaluate the sensitivity of our results to instrument strength. Based on linear regressions, higher BMI was associated with a higher prevalence of depression symptoms among females (b = 0.238, p = 0.000) and males (b = 0.117, p = 0.019). However, the MR results imply that the positive link applies only to females (b = 0.302, p = 0.007) but not to males (b = -0.070, p = 0.520). Poor instrument strength may explain why many previous studies that have utilized genetic instruments have been unable to identify a statistically significant link between BMI and depression-related traits. Although the number of genetic markers in the instrument had only a minor effect on the point estimates, the standard errors were much smaller when more powerful instruments were employed.
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The Young Finns Study has been financially supported by the Academy of Finland: grant numbers 356405, 322098, 286284, 134309 (Eye), 126925, 121584, 124282, 129378 (Salve), 117787 (Gendi), and 41071 (Skidi); the Social Insurance Institution of Finland; Competitive State Research Financing of the Expert Responsibility area of Kuopio; Tampere and Turku University Hospitals (grant number X51001); Juho Vainio Foundation; Paavo Nurmi Foundation; Finnish Foundation for Cardiovascular Research; Finnish Cultural Foundation; Sigrid Juselius Foundation; Tampere Tuberculosis Foundation; Emil Aaltonen Foundation; Yrjö Jahnsson Foundation; Signe and Ane Gyllenberg Foundation; Jenny and Antti Wihuri Foundation; Diabetes Research Foundation of Finnish Diabetes Association; EU Horizon 2020 (grant 755320 for TAXINOMISIS and grant 848146 for To Aition); European Research Council (grant number 742927 for MULTIEPIGEN project); Tampere University Hospital Supporting Foundation; Society of Finnish Clinical Chemistry; Cancer Foundation Finland; BETTER4U (Preventing obesity through Biologically and bEhaviorally Tailored inTERventions for you; project number: 101080117); Jane and Aatos Erkko Foundation. The use of linked data was supported by Palkansaajasäätiö and OP Group Research Foundation. ME was supported by the Academy of Finland (339390). ...License
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