There appears to be an issue with the SNPs reported in this paper in that they do not match the SNPs reported in the referenced MDD study, and curiously, every single SNP in this paper has been associated with BMI or obesity in other papers.
The paper says:
> Associations between single-nucleotide polymorphisms (SNPs) and MDD were estimated using data from the largest published GWAS meta-analysis of European ancestry to date[8]. [...] Following a meticulous reconciliation of exposure and outcome data, a subset of 57 SNPs, which exhibited the strongest associations with MDD and had the highest levels of statistical confidence, were selected as IVs for the subsequent MR analysis.
[8] is Howard, D. M. et al. Genome-wide meta-analysis of depression identifies 102 independent variants and highlights the importance of the prefrontal brain regions. _Nat. Neurosci. vol_. **22** (3), 343–352. [
https://doi.org/10.1038/s41593-018-0326-7](https://doi.org/10.1038/s41593-018-0326-7) (2019).
Supplementary Material 1 has a list of 57 SNPs, which the paper says were chosen based on strong associations with MDD in Howard et al. Supplementary Table 1 from the Howard et al paper lists 102 variants that were found to be associated with MDD. There is no overlap between the SNPs reported in these papers.
All SNPs listed in Song et al have previously been reported to be associated with BMI or obesity, and can all be found mentioned as such among the following papers:
- Li, J., Tian, A., Zhu, H., Chen, L., Wen, J., Liu, W., & Chen, P. (2022). Mendelian Randomization Analysis Reveals No Causal Relationship Between Nonalcoholic Fatty Liver Disease and Severe COVID-19. _Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association_, _20_(7), 1553–1560.e78.
https://doi.org/10.1016/j.cgh.2022.01.045
- Garfield, V., Llewellyn, C. H., Wichstrøm, L., & Steinsbekk, S. (2021). Shared genetic architecture underlying sleep and weight in children. _Sleep medicine_, _83_, 40–44.
https://doi.org/10.1016/j.sleep.2021.04.021
- Shimaoka, I., Kamide, K., Ohishi, M., Katsuya, T., Akasaka, H., Saitoh, S., Sugimoto, K., Oguro, R., Congrains, A., Fujisawa, T., Shimamoto, K., Ogihara, T., & Rakugi, H. (2010). Association of gene polymorphism of the fat-mass and obesity-associated gene with insulin resistance in Japanese. _Hypertension research : official journal of the Japanese Society of Hypertension_, _33_(3), 214–218.
https://doi.org/10.1038/hr.2009.215
- Fall, T., Hägg, S., Ploner, A., Mägi, R., Fischer, K., Draisma, H. H., Sarin, A. P., Benyamin, B., Ladenvall, C., Åkerlund, M., Kals, M., Esko, T., Nelson, C. P., Kaakinen, M., Huikari, V., Mangino, M., Meirhaeghe, A., Kristiansson, K., Nuotio, M. L., Kobl, M., … ENGAGE Consortium (2015). Age- and sex-specific causal effects of adiposity on cardiovascular risk factors. _Diabetes_, _64_(5), 1841–1852.
https://doi.org/10.2337/db14-0988
- Nikpay, M., Turner, A. W., & McPherson, R. (2018). Partitioning the Pleiotropy Between Coronary Artery Disease and Body Mass Index Reveals the Importance of Low Frequency Variants and Central Nervous System-Specific Functional Elements. _Circulation. Genomic and precision medicine_, _11_(2), e002050.
https://doi.org/10.1161/CIRCGEN.117.002050
- He, Y., Zheng, C., He, M. H., & Huang, J. R. (2021). The Causal Relationship Between Body Mass Index and the Risk of Osteoarthritis. _International journal of general medicine_, _14_, 2227–2237.
https://doi.org/10.2147/IJGM.S314180
- Beckers, S., Peeters, A., Zegers, D., Mertens, I., Van Gaal, L., & Van Hul, W. (2008). Association of the BDNF Val66Met variation with obesity in women. _Molecular genetics and metabolism_, _95_(1-2), 110–112.
https://doi.org/10.1016/j.ymgme.2008.06.008
- Young, A. I., Wauthier, F. L., & Donnelly, P. (2018). Identifying loci affecting trait variability and detecting interactions in genome-wide association studies. _Nature genetics_, _50_(11), 1608–1614.
https://doi.org/10.1038/s41588-018-0225-6
