GWAS of depression in 4,520 individuals from the Russian population highlights the role of MAGI2 (S-SCAM) in the gut-brain axis

Frontiers in Genetics. 2023. Vol. 13. P. 972196–972196.

Pinakhina D., Yermakovich D., Vergasova E., Kasyanov E., Rukavishnikov G., Rezapova V., Kolosov N., Sergushichev A., Popov I., Kovalenko E., Ilinskaya A., Kim A., Plotnikov N., Ilinsky V., Neznanov N., Mazo G., Kibitov A., Rakitko A., Artomov M.

We present the results of the depression Genome-wide association studies study performed on a cohort of Russian-descent individuals, which identified a novel association at chromosome 7q21 locus. Gene prioritization analysis based on already known depression risk genes indicated MAGI2 (S-SCAM) as the most probable gene from the locus and potential susceptibility gene for the disease. Brain and gut expression patterns were the main features highlighting functional relatedness of MAGI2 to the previously known depression risk genes. Local genetic covariance analysis, analysis of gene expression, provided initial suggestive evidence of hospital anxiety and depression scale and diagnostic and statistical manual of mental disorders scales having a different relationship with gut-brain axis disturbance. It should be noted, that while several independent methods successfully in silico validate the role of MAGI2, we were unable to replicate genetic association for the leading variant in the MAGI2 locus, therefore the role of rs521851 in depression should be interpreted with caution.

Keywords: depression, GWAS, HADS-D, gut brain axis, gene discovery