Results of a pilot genome-wide association study (GWAS) and polygenic depression risk scales in the Russian population using online phenotyping

Aleksandr Olegovich Kibitov; Aleksandr Sergeevich Rakit'ko; Evgeniy Dmitrievich Kas'yanov; Grigoriy Viktorovich Rukavishnikov; Andrey Aleksandrovich Kibitov; Danat Ermakovich; Kira Aleksandrovna Kozlova; Valeriy Vladimirovich Il'inskiy; Larisa Vladimirovna Malyshko; Aleksandr Borisovich Shmukler; Vera Evgen'evna Golimbet; Nikolay Grigor'evich Neznanov; Galina Elevna Mazo

doi:10.47877/1560-957Х-2022-10502

Results of a pilot genome-wide association study (GWAS) and polygenic depression risk scales in the Russian population using online phenotyping

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Kibitov AO, Rakit'ko AS, Kas'yanov ED, et al. [Results of a pilot genome-wide association study (GWAS) and polygenic depression risk scales in the Russian population using online phenotyping]. Rossiiskii psikhiatricheskii zhurnal [Russian Journal of Psychiatry]. 2022;(5):13-29. Russian

Abstract

In this cross-sectional association study of the case-control type with the aim of developing a genetic test system based on polygenic risk scores (PRS) for major depression, the method of online phenotyping of depression and anxiety was tested using the Hospital Anxiety and Depression Scale (HADS) questionnaire and the original questionnaire based on the DSM-5 diagnostic interview criteria. In a population sample (n=2540), genome-wide association studies (GWAS) and analysis of PRSs were performed using summary statistics of the largest GWAS of depression and a number of other mental disorders. The most significant protective marker was identified for the HADS-D total score (depression) phenotype rs9517934 (β=–0.4041, р=2.277*10^–7) in the long noncoding RNA gene. The resulting PRSs were tested in a clinical sample (n=336). The PRS based on the GWAS meta-analysis of depression for 71% of the study phenotypes had the highest predictive power for depression, with the highest PRS power for the HADS-A total Score (anxiety) quantitative phenotype (β=0.36561, p=0.0031, AUC=0.6137).

Keywords depression; anxiety; GWAS; HADS; DSM; polygenic risk scores; prophylaxis

References

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