MTHFR, NR3C1, FKBP5, and CRHR1 gene polymorphisms are strongly associated with depressive disorder susceptibility: A meta-analysis and power analysis

Abstract

Depression is a polygenic and complex condition; however, most genetic analyses have yielded insignificant associations between candidate genes and depressive disorder. This is primarily due to the lack of reproducible findings in genome-wide association studies (GWAS). In this meta-analysis, we extensively investigated the implications of genetic polymorphisms in seven candidate genes for depression. We conducted a thorough search of electronic databases, including Google Scholar, Cochrane, PubMed, Medline, Embase, and PsycINFO, covering data from January 1997 to 2022. Our search identified approximately 3,500 published research papers related to this study. Among these, 81 studies met our eligibility criteria and focused on the six genes under study. These selected candidate genes for our meta-analysis included NR3C1, MTHFR, FKBP5, CRHR1, COMT, and TNF-α. The results of our meta-analysis on genetic polymorphisms indicate a significant association with depression at the 95% confidence interval (CI). When categorizing outcomes by different ethnic groups, our findings reveal significant results (p=<0.05) for Asian and Caucasian populations. This current meta-analysis provides valuable insights that can facilitate the use of these significantly associated genes for diagnosing the severity of depression or as indicators for treatment modalities in depression conditions.