Moderators of gene-outcome associations following traumatic brain injury. (November 2021)

• Record Type: Journal Article
• Authors: Carmichael, Jai; Hicks, Amelia J.; Spitz, Gershon; Gould, Kate Rachel; Ponsford, Jennie
• Is Part Of: Neuroscience and biobehavioral reviews. Volume 130(2021)
• Page Start: 107
• Page End: 124
• Publication Date: 2021-11
• Subjects: Genetics -- Traumatic brain injury -- Age -- Sex -- Ethnicity -- Apolipoprotein E -- APOE -- Brain-derived neurotrophic factor -- BDNF -- Catechol-O-methyltransferase -- COMT -- Precision medicine -- Antagonistic pleiotropy -- Dopamine -- Estrogen; Psychophysiology -- Periodicals; Human behavior -- Periodicals; Animal behavior -- Periodicals; Neurology -- Periodicals; Behavior -- Periodicals; Ethology -- Periodicals; Neurology -- Periodicals; Psychophysiologie -- Périodiques; Comportement humain -- Périodiques; Animaux -- Mœurs et comportement -- Périodiques; Neurologie -- Périodiques; Animal behavior; Human behavior; Neurology; Psychophysiology; Periodicals; Electronic journals; 573.8
• DOI: 10.1016/j.neubiorev.2021.08.015
• Languages: English
• ISSNs: 0149-7634

Abstract

Highlights: Traumatic brain injury under complex polygenic influence. APOE, BDNF, and COMT key genes. Understanding factors that moderate genetic associations can improve patient care. Speculative mechanisms of gene-outcome moderation by age, biological sex, ethnicity. Recommendations for future genetics research in TBI and other populations. Abstract: The field of genomics is the principal avenue in the ongoing development of precision/personalised medicine for a variety of health conditions. However, relating genes to outcomes is notoriously complex, especially when considering that other variables can change, or moderate, gene-outcome associations. Here, we comprehensively discuss moderation of gene-outcome associations in the context of traumatic brain injury (TBI), a common, chronically debilitating, and costly neurological condition that is under complex polygenic influence. We focus our narrative review on single nucleotide polymorphisms (SNPs) of three of the most studied genes ( apolipoprotein E, brain-derived neurotrophic factor, and catechol-O-methyltransferase ) and on three demographic variables believed to moderate associations between these SNPs and TBI outcomes ( age, biological sex, and ethnicity ). We speculate on the mechanisms which may underlie these moderating effects, drawing widely from biomolecular and behavioural research ( n = 175 scientific reports) within the TBI population ( n = 72) and other neurological, healthy, ageing, and psychiatric populations ( n = 103). We conclude with methodological recommendations for improved exploration of moderators in future genetics research in TBI and other populations.