Approaching “Phantom Heritability” in Psychiatry by Hypothesis-Driven Gene–Gene Interactions

Rovaris, Diego Luiz; Mota, Nina Roth; Callegari-Jacques, Sídia Maria; Bau, Claiton H.D.

doi:10.3389/fnhum.2013.00210

Cited by 7 publications

(3 citation statements)

References 14 publications

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“…In summary, the results from this study revealed genes and biological processes that may underlie differences between SZ and BD, supporting the hypothesis that SZ and BD arise from shared genetic factors, but that the resulting clinical phenotype is modulated by additional alterations mediated by microglia, possibly caused by interference of environmental factors at different times during neurodevelopment and early life, and/or epistatic interactions among groups of genes and environment (Rovaris et al, 2013). Our study has limitations since the expression data was provided from post-mortem brain samples and because patients had been medicated.…”

Section: Discussionsupporting

confidence: 57%

Innate immune response is differentially dysregulated between bipolar disease and schizophrenia

Baumont

Maschietto

Lima

et al. 2015

Schizophrenia Research

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Schizophrenia (SZ) and bipolar disorder (BD) are severe psychiatric conditions with a neurodevelopmental component. Genetic findings indicate the existence of an overlap in genetic susceptibility across the disorders. Also, image studies provide evidence for a shared neurobiological basis, contributing to a dimensional diagnostic approach. This study aimed to identify the molecular mechanisms that differentiate SZ and BD patients from health controls but also that distinguish both from health individuals. Comparison of gene expression profiling in post-mortem brains of both disorders and health controls (30 cases), followed by a further comparison between 29 BD and 29 SZ revealed 28 differentially expressed genes. These genes were used in co-expression analysesthat revealed the pairs CCR1/SERPINA1, CCR5/HCST, C1QA/CD68, CCR5/S100A11 and SERPINA1/TLR1 as presenting the most significant difference in co-expression between SZ and BD. Next, a protein-protein interaction (PPI) network using the 28 differentially expressed genes as seeds revealed CASP4, TYROBP, CCR1, SERPINA1, CCR5 and C1QA as having a central role in the diseases manifestation. Both co-expression and network topological analyses pointed to genes related to microglia functions. Based on this data, we suggest that differences between SZ and BP are due to genes involved with response to stimulus, defense response, immune system process and response to stress biological processes, all having a role in the communication of environmental factors to the cells and associated to microglia.

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Section: Discussionsupporting

confidence: 57%

Innate immune response is differentially dysregulated between bipolar disease and schizophrenia

Baumont

Maschietto

Lima

et al. 2015

Schizophrenia Research

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“…For this reason, the use of previous knowledge about protein-protein interactions to design hypothesis to evaluate gene-gene interactions in candidate gene studies may contribute to the understanding of the biological underpinnings of psychiatric disorders. In this way, our evidencebased approach aims to limit the risk of false-positive in line with the growing field of proteineprotein interactions (Rovaris et al, 2013a), at least until GWAS consortiums achieve robust sample sizes to evaluated epistasis in high-throughput analyses (Rovaris et al, 2014).…”

Section: Discussionmentioning

confidence: 98%

Corticosteroid receptor genes and childhood neglect influence susceptibility to crack/cocaine addiction and response to detoxification treatment

Rovaris

Mota

Bertuzzi

et al. 2015

Journal of Psychiatric Research

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“…In the last decade, interest has been generated in studying G-E and gene-gene interactions 72 in psychoactive substance addiction through the association between childhood neglect and polymorphism of the mineralocorticoid (NR3C2) and glucocorticoid (NR3C1) genes [73][74][75] . In this sense, Rovaris et al evaluated 139 cocaine-addicted women in the withdrawal period, finding a significant interaction between the rs5522 allele of NR3C2 and lack of infant physical contact, which altered the risk of cocaine addiction (OR = 4.0, p= 0.001).…”

Section: Cocainementioning

confidence: 99%

Etiopatogenia de las drogodependencias: una síntesis explicativa desde una perspectiva epigenética

Miranda

Palomino²,

Arismendy-López³

et al. 2022

medupb

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El consumo de sustancias con potencial adictivo es un problema relevante de salud. La evidencia científica sugiere que los mecanismos subyacentes que regulan los procesos comportamentales en las adicciones involucran un complejo interjuego entre factores genéticos y ambientales. Por lo tanto, esta revisión narrativa tiene como objetivo aportar un marco de referencia que permita sintetizar la evidencia sobre interacciones genes- ambiente-agente desde la perspectiva de la historia natural de la enfermedad y los estadios del proceso adictivo para: alcohol, nicotina, cannabis, psicoestimulantes y opioides. En esta revisión realizamos una búsqueda exhaustiva de la literatura sin límites de tiempo en PubMed, Ebsco, Lilacs y SciELO, revisando el título y el resumen se seleccionaron artículos originales en humanos o animales que abordaran la etiología de las adiciones según el enfoque metodológico de interacción entre genes y ambiente (G-A), incluyendo artículos en español, inglés y portugués. Los estudios genéticos han revelado el papel crítico de los modificadores epigenéticos (acetilación de las histonas) en mantener la homeóstasis cerebral en condiciones patológicas y enfocarse en las interacciones G-A también permitirá caracterizar subgrupos (basados en los factoresambientales) de alto riesgo para conductas adictivas que pueden ser objeto de intervenciones específicas, por lo que, las estrategias de tratamiento deben englobar una combinación de intervenciones psicosociales con terapia génica que involucren las manipulaciones farmacológicas de las histonas que pueden contribuir a diseñar mejores terapias y tal vez conducir a un manejo más exitoso de las drogodependencias.

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Approaching “Phantom Heritability” in Psychiatry by Hypothesis-Driven Gene–Gene Interactions

Cited by 7 publications

References 14 publications

Innate immune response is differentially dysregulated between bipolar disease and schizophrenia

Innate immune response is differentially dysregulated between bipolar disease and schizophrenia

Corticosteroid receptor genes and childhood neglect influence susceptibility to crack/cocaine addiction and response to detoxification treatment

Etiopatogenia de las drogodependencias: una síntesis explicativa desde una perspectiva epigenética

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