{"title":"Polygene by environment interactions predicting depressive outcomes","authors":"Alessandra R. Grillo","doi":"10.1002/ajmg.b.33000","DOIUrl":null,"url":null,"abstract":"<p>Depression is a major public health problem with a continued need to uncover its etiology. Current models of depression contend that gene-by-environment (G × E) interactions influence depression risk, and further, that depression is polygenic. Thus, recent models have emphasized two polygenic approaches: a hypothesis-driven multilocus genetic profile score (MGPS; “MGPS × E”) and a polygenic risk score (PRS; “PRS × E”) derived from genome-wide association studies (GWAS). This review for the first time synthesizes current knowledge on polygene by environment “P × E” interaction research predicting primarily depression-related outcomes, and in brief, neurobiological outcomes. The “environment” of focus in this project is stressful life events. It further discusses findings in the context of differential susceptibility and diathesis-stress theories—two major theories guiding G × E work. This synthesis indicates that, within the MGPS literature, polygenic scores based on the serotonin system, the HPA axis, or across multiple systems, interact with environmental stress exposure to predict outcomes at multiple levels of analyses and most consistently align with differential susceptibility theory. Depressive outcomes are the most studied, but neuroendocrine, and neuroimaging findings are observed as well. By contrast, vast methodological differences between GWAS-based PRS studies contribute to mixed findings that yield inconclusive results.</p>","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":"198 1","pages":""},"PeriodicalIF":1.6000,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajmg.b.33000","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/ajmg.b.33000","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
引用次数: 0
Abstract
Depression is a major public health problem with a continued need to uncover its etiology. Current models of depression contend that gene-by-environment (G × E) interactions influence depression risk, and further, that depression is polygenic. Thus, recent models have emphasized two polygenic approaches: a hypothesis-driven multilocus genetic profile score (MGPS; “MGPS × E”) and a polygenic risk score (PRS; “PRS × E”) derived from genome-wide association studies (GWAS). This review for the first time synthesizes current knowledge on polygene by environment “P × E” interaction research predicting primarily depression-related outcomes, and in brief, neurobiological outcomes. The “environment” of focus in this project is stressful life events. It further discusses findings in the context of differential susceptibility and diathesis-stress theories—two major theories guiding G × E work. This synthesis indicates that, within the MGPS literature, polygenic scores based on the serotonin system, the HPA axis, or across multiple systems, interact with environmental stress exposure to predict outcomes at multiple levels of analyses and most consistently align with differential susceptibility theory. Depressive outcomes are the most studied, but neuroendocrine, and neuroimaging findings are observed as well. By contrast, vast methodological differences between GWAS-based PRS studies contribute to mixed findings that yield inconclusive results.
期刊介绍:
Neuropsychiatric Genetics, Part B of the American Journal of Medical Genetics (AJMG) , provides a forum for experimental and clinical investigations of the genetic mechanisms underlying neurologic and psychiatric disorders. It is a resource for novel genetics studies of the heritable nature of psychiatric and other nervous system disorders, characterized at the molecular, cellular or behavior levels. Neuropsychiatric Genetics publishes eight times per year.