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Dialogues in Clinical Neuroscience Sep 2012The aim of this review is to summarize the key findings from genetic and epidemiological research, which show that autism is a complex disorder resulting from the... (Review)
Review
The aim of this review is to summarize the key findings from genetic and epidemiological research, which show that autism is a complex disorder resulting from the combination of genetic and environmental factors. Remarkable advances in the knowledge of genetic causes of autism have resulted from the great efforts made in the field of genetics. The identification of specific alleles contributing to the autism spectrum has supplied important pieces for the autism puzzle. However, many questions remain unanswered, and new questions are raised by recent results. Moreover, given the amount of evidence supporting a significant contribution of environmental factors to autism risk, it is now clear that the search for environmental factors should be reinforced. One aspect of this search that has been neglected so far is the study of interactions between genes and environmental factors.
Topics: Autistic Disorder; Environment; Gene Dosage; Gene-Environment Interaction; Genetic Predisposition to Disease; Humans; Molecular Epidemiology; Risk Factors
PubMed: 23226953
DOI: 10.31887/DCNS.2012.14.3/pchaste -
Current Psychiatry Reports Sep 2019We review recent developments on risk factors in schizophrenia. (Review)
Review
PURPOSE OF REVIEW
We review recent developments on risk factors in schizophrenia.
RECENT FINDINGS
The way we think about schizophrenia today is profoundly different from the way this illness was seen in the twentieth century. We now know that the etiology of schizophrenia is multifactorial and reflects an interaction between genetic vulnerability and environmental contributors. Environmental risk factors such as pregnancy and birth complications, childhood trauma, migration, social isolation, urbanicity, and substance abuse, alone and in combination, acting at a number of levels over time, influence the individual's likelihood to develop the disorder. Environmental risk factors together with the identification of a polygenic risk score for schizophrenia, research on gene-environment interaction and environment-environment interaction have hugely increased our knowledge of the disorder.
Topics: Female; Gene-Environment Interaction; Humans; Multifactorial Inheritance; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; Risk Factors; Schizophrenia; Substance-Related Disorders
PubMed: 31522306
DOI: 10.1007/s11920-019-1091-3 -
Genes Nov 2021Schizophrenia is a devastating mental illness with a strong genetic component that is the subject of extensive research. Despite the high heritability, it is well... (Review)
Review
Schizophrenia is a devastating mental illness with a strong genetic component that is the subject of extensive research. Despite the high heritability, it is well recognized that non-genetic factors such as certain infections, cannabis use, psychosocial stress, childhood adversity, urban environment, and immigrant status also play a role. Whenever genetic and non-genetic factors co-exist, interaction between the two is likely. This means that certain exposures would only be of consequence given a specific genetic makeup. Here, we provide a brief review of studies reporting evidence of such interactions, exploring genes and variants that moderate the effect of the environment to increase risk of developing psychosis. Discovering these interactions is crucial to our understanding of the pathogenesis of complex disorders. It can help in identifying individuals at high risk, in developing individualized treatments and prevention plans, and can influence clinical management.
Topics: Animals; Gene-Environment Interaction; Humans; Psychotic Disorders; Risk Factors; Schizophrenia
PubMed: 34946799
DOI: 10.3390/genes12121850 -
Essays in Biochemistry Dec 2019DNA methylation is an epigenetic mark involved in regulating genome function and is critical for normal development in mammals. It has been observed that the... (Review)
Review
DNA methylation is an epigenetic mark involved in regulating genome function and is critical for normal development in mammals. It has been observed that the developmental environment can lead to permanent changes in gene expression and DNA methylation, at least at 'metastable epialleles'. These are defined as regions of the genome that show a variable epigenetic state that is established early in development and maintained through subsequent cell divisions. However, the majority of the known genome does not behave in this manner. Here, we use the developmental origins of adult disease hypothesis to understand environmental epigenomics. Some challenges to studying how DNA methylation is influenced by the environment include identifying DNA methylation changes associated with an environmental exposure in tissues with a complex cellular composition and at genomic regions for which DNA methylation is dynamically regulated in a cell-type specific manner. We also offer a perspective of how emerging technologies may be useful for dissecting the functional contribution of exposure-associated epigenetic changes and highlight recent evidence that suggests that genomic regions that are absent from genome assemblies may be unappreciated hotspots for environmental modulation of the epigenetic state.
Topics: Animals; DNA; DNA Methylation; Epigenesis, Genetic; Gene-Environment Interaction; Humans
PubMed: 31782496
DOI: 10.1042/EBC20190031 -
Revue Neurologique Dec 2019Genetic factors only account for up to a third of the cases of Parkinson's disease (PD), while the remaining cases are of unknown aetiology. Environmental exposures... (Review)
Review
Genetic factors only account for up to a third of the cases of Parkinson's disease (PD), while the remaining cases are of unknown aetiology. Environmental exposures (such as pesticides or heavy metals) and the interaction with genetic susceptibility factors (summarized in the concept of impaired xenobiotic metabolism) are believed to play a major role in the mechanisms of neurodegeneration. Beside of the classical association studies (e.g. genome-wide association studies), a novel approach to investigate environmental risk factors are Mendelian randomisation studies. This review explores the gene-environment interaction and the gain of Mendelian randomisation studies in assessing causalities of modifiable risk factors for PD.
Topics: Environmental Exposure; Environmental Pollutants; Gene-Environment Interaction; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Mendelian Randomization Analysis; Parkinson Disease; Risk Factors
PubMed: 31543362
DOI: 10.1016/j.neurol.2019.04.010 -
Dialogues in Clinical Neuroscience Jun 2017This review serves as a systematic guide to the genetics of generalized anxiety disorder (GAD) and further focuses on anxiety-relevant endophenotypes, such as... (Review)
Review
This review serves as a systematic guide to the genetics of generalized anxiety disorder (GAD) and further focuses on anxiety-relevant endophenotypes, such as pathological worry fear of uncertainty, and neuroticism. We inspect clinical genetic evidence for the familialityl heritability of GAD and cross-disorder phenotypes based on family and twin studies. Recent advances of linkage studies, genome-wide association studies, and candidate gene studies (eg, ) are outlined. Functional and structural neuroimaging and neurophysiological readouts relating to peripheral stress markers and psychophysiology are further integrated, building a multilevel disease framework. We explore etiologic factors in gene-environment interaction approaches investigating childhood trauma, environmental adversity, and stressful life events in relation to selected candidate genes (), Additionally, the pharmacogenetics of selective serotonin reuptake inhibitor/serotonin-norepinephrine reuptake inhibitor treatment are summarized (). Finally, GAD and trait anxiety research challenges and perspectives in the field of genetics, including epigenetics, are discussed.
Topics: Anxiety; Anxiety Disorders; Gene-Environment Interaction; Genome-Wide Association Study; Humans; Neuroimaging; Norepinephrine; Phenotype; Selective Serotonin Reuptake Inhibitors
PubMed: 28867940
DOI: 10.31887/DCNS.2017.19.2/kdomschke -
Toxicological Sciences : An Official... Oct 2018
Review
Topics: Animals; Biological Evolution; Carcinogenesis; Gene-Environment Interaction; Humans; Neoplasms
PubMed: 30629266
DOI: 10.1093/toxsci/kfy184 -
Genes Aug 2023Orofacial clefting is considered one of the commonest birth defects worldwide. It presents as cleft lip only, isolated cleft palate or cleft lip and palate. The... (Review)
Review
Orofacial clefting is considered one of the commonest birth defects worldwide. It presents as cleft lip only, isolated cleft palate or cleft lip and palate. The condition has a diverse genetic background influenced by gene-gene and gene-environment interaction, resulting in two main types, syndromic and nonsyndromic orofacial clefts. Orofacial clefts lead to significant physiological difficulties that affect feeding, speech and language development and other developmental aspects, which results in an increased social and financial burden on the affected individuals and their families. The management of cleft lip and palate is solely based on following a multidisciplinary team approach. In this narrative review article, we briefly summarize the different genetic causes of orofacial clefts and discuss some of the common syndromes and the approach to the management of orofacial clefts.
Topics: Humans; Cleft Lip; Cleft Palate; Gene-Environment Interaction; Genetic Background
PubMed: 37628654
DOI: 10.3390/genes14081603 -
Neuroscience and Biobehavioral Reviews Feb 2017The differential susceptibility model states that a given genetic variant is associated with an increased risk of pathology in negative environments but greater than... (Review)
Review
The differential susceptibility model states that a given genetic variant is associated with an increased risk of pathology in negative environments but greater than average resilience in enriched ones. While this theory was first implemented in psychiatric-genetic research, it may also help us to unravel the complex ways that genes and environments interact to influence feeding behavior and obesity. We reviewed evidence on gene vs. environment interactions that influence obesity development, aiming to support the applicability of the differential susceptibility model for this condition, and propose that various environmental "layers" relevant for human development should be considered when bearing the differential susceptibility model in mind. Mother-child relationship, socioeconomic status and individual's response are important modifiers of BMI and food intake when interacting with gene variants, "for better and for worse". While only a few studies to date have investigated obesity outcomes using this approach, we propose that the differential susceptibility hypothesis is in fact highly applicable to the study of genetic and environmental influences on feeding behavior and obesity risk.
Topics: Disease Susceptibility; Environment; Feeding Behavior; Gene-Environment Interaction; Humans; Obesity
PubMed: 28024828
DOI: 10.1016/j.neubiorev.2016.12.028 -
Perspectives on Psychological Science :... Jan 2015Studying how genetic predispositions come together with environmental factors to contribute to complex behavioral outcomes has great potential for advancing the... (Review)
Review
Studying how genetic predispositions come together with environmental factors to contribute to complex behavioral outcomes has great potential for advancing the understanding of the development of psychopathology. It represents a clear theoretical advance over studying these factors in isolation. However, research at the intersection of multiple fields creates many challenges. We review several reasons why the rapidly expanding candidate gene-environment interaction (cG×E) literature should be considered with a degree of caution. We discuss lessons learned about candidate gene main effects from the evolving genetics literature and how these inform the study of cG×E. We review the importance of the measurement of the gene and environment of interest in cG×E studies. We discuss statistical concerns with modeling cG×E that are frequently overlooked. Furthermore, we review other challenges that have likely contributed to the cG×E literature being difficult to interpret, including low power and publication bias. Many of these issues are similar to other concerns about research integrity (e.g., high false-positive rates) that have received increasing attention in the social sciences. We provide recommendations for rigorous research practices for cG×E studies that we believe will advance its potential to contribute more robustly to the understanding of complex behavioral phenotypes.
Topics: Animals; Gene-Environment Interaction; Genetic Research; Humans; Research Design
PubMed: 25620996
DOI: 10.1177/1745691614556682