scholarly journals Concepts in Multifactorial Etiology of Developmental Disorders: Gene-Gene and Gene-Environment Interactions in Holoprosencephaly

2021 ◽  
Vol 9 ◽  
Author(s):  
Hsiao-Fan Lo ◽  
Mingi Hong ◽  
Robert S. Krauss
Keyword(s):  
Risk Factors ◽  
Environmental Risk ◽  
Developmental Disorders ◽  
Heart Defects ◽  
Genomic Analysis ◽  
Environmental Risk Factors ◽  
Embryonic Patterning ◽  
Mechanistic Studies ◽  
Gene Environment ◽  
Oligogenic Inheritance

Many common developmental disorders are thought to arise from a complex set of genetic and environmental risk factors. These factors interact with each other to affect the strength and duration of key developmental signaling pathways, thereby increasing the possibility that they fail to achieve the thresholds required for normal embryonic patterning. One such disorder, holoprosencephaly (HPE), serves as a useful model system in understanding various forms of multifactorial etiology. Genomic analysis of HPE cases, epidemiology, and mechanistic studies of animal models have illuminated multiple potential ways that risk factors interact to produce adverse developmental outcomes. Among these are: 1) interactions between driver and modifier genes; 2) oligogenic inheritance, wherein each parent provides predisposing variants in one or multiple distinct loci; 3) interactions between genetic susceptibilities and environmental risk factors that may be insufficient on their own; and 4) interactions of multiple genetic variants with multiple non-genetic risk factors. These studies combine to provide concepts that illuminate HPE and are also applicable to additional disorders with complex etiology, including neural tube defects, congenital heart defects, and oro-facial clefting.

scholarly journals Non-Genetic Factors in Schizophrenia

2019 ◽  
Vol 21 (10) ◽  
Author(s):  
Simona A. Stilo ◽  
Robin M. Murray
Keyword(s):  
Risk Factors ◽  
Environmental Risk ◽  
Environmental Risk Factors ◽  
Polygenic Risk Score ◽  
Environment Interaction ◽  
Birth Complications ◽  
Gene Environment Interaction ◽  
Gene Environment ◽  
Recent Developments ◽  
The Way

Abstract 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. Summary 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.

scholarly journals Gene–environment interaction: New insights into perceived parenting and social anxiety among adolescents

2020 ◽  
Vol 63 (1) ◽  
Author(s):  
Viktoria Chubar ◽  
Karla Van Leeuwen ◽  
Patricia Bijttebier ◽  
Evelien Van Assche ◽  
Guy Bosmans ◽  
...  
Keyword(s):  
Mental Health ◽  
Risk Factors ◽  
Social Anxiety ◽  
Environmental Risk ◽  
Mental Health Problems ◽  
Environmental Risk Factors ◽  
Biological Pathways ◽  
Anxiety Symptoms ◽  
Perceived Parenting ◽  
Gene Environment

Abstract Background. Social anxiety symptoms (SAS) are among the most common mental health problems during adolescence, and it has been shown that parenting influences the adolescent’s level of social anxiety. In addition, it is now widely assumed that most mental health problems, including social anxiety, originate from a complex interplay between genes and environment. However, to date, gene–environment (G × E) interactions studies in the field of social anxiety remain limited. In this study, we have examined how 274 genes involved in different neurotransmission pathways interact with five aspects of perceived parenting as environmental exposure (i.e., support, proactive control, psychological control, punitive control, and harsh punitive control) to affect SAS during adolescence. Methods. We have applied an analytical technique that allows studying genetic information at the gene level, by aggregating data from multiple single-nucleotide-polymorphisms within the same gene and by taking into account the linkage disequilibrium structure of the gene. All participants were part of the STRATEGIES cohort of 948 Flemish adolescents (mean age = 13.7), a population-based study on the development of problem behaviors in adolescence. Relevant genes were preselected based on prior findings and neurotransmitter-related functional protein networks. Results. The results suggest that genes involved in glutamate (SLC1A1), glutathione neurotransmission (GSTZ1), and oxidative stress (CALCRL), in association with harsh punitive parenting, may contribute to social anxiety in adolescence. Isolated polymorphisms in these genes have been related to anxiety and related disorders in earlier work.Conclusions: Taken together, these findings provide new insights into possible biological pathways and environmental risk factors involved in the etiology of social anxiety symptoms’ development. Conclusions. Taken together, these findings provide new insights into possible biological pathways and environmental risk factors involved in the etiology of social anxiety symptoms’ development.

scholarly journals Selected environmental risk factors and congenital heart defects

Medicina ◽  
2008 ◽  
Vol 44 (11) ◽  
pp. 827 ◽  
Author(s):  
Renata Kučienė ◽  
Virginija Dulskienė
Keyword(s):  
Risk Factors ◽  
Congenital Heart Defects ◽  
Environmental Risk ◽  
Congenital Heart ◽  
Heart Defects ◽  
Maternal Diabetes ◽  
Epidemiological Studies ◽  
Environmental Risk Factors ◽  
Congenital Heart Malformations ◽  
Genetic And Environmental Factors

The aim of the article is to review the published scientific literature and epidemiological studies about the effect of selected environmental risk factors on congenital heart defects in infants. According to recent reports, the prevalence of congenital heart defects is around 1% of live births. Congenital heart malformations are the leading cause of infant mortality. Unfortunately, the majority of the causes of heart defects remain unknown. These malformations are caused by interaction of genetic and environmental factors. The article reviews selected environmental risk factors: maternal illnesses and conditions associated with metabolic disorder (maternal diabetes, obesity, phenylketonuria), maternal lifestyle factors (alcohol use, smoking), which may increase the risk of congenital heart defects.

Identifying environmental risk factors and gene–environment interactions in holoprosencephaly

2020 ◽  
Vol 113 (1) ◽  
pp. 63-76
Author(s):  
Yonit A. Addissie ◽  
Angela Troia ◽  
Zoe C. Wong ◽  
Joshua L. Everson ◽  
Beth A. Kozel ◽  
...  
Keyword(s):  
Risk Factors ◽  
Environmental Risk ◽  
Environmental Risk Factors ◽  
Gene Environment

scholarly journals An Exploration of Gene–Environment Interaction and Asthma in a Large Sample of 5-Year-Old Dutch Twins

2008 ◽  
Vol 11 (2) ◽  
pp. 143-149 ◽  
Author(s):  
Toos C. E. M. van Beijsterveldt ◽  
Dorret I. Boomsma
Keyword(s):  
Risk Factors ◽  
Child Care ◽  
Environmental Risk ◽  
Premature Birth ◽  
Family Members ◽  
Twin Studies ◽  
Environmental Risk Factors ◽  
Environment Interaction ◽  
Gene Environment Interaction ◽  
Gene Environment

AbstractA consistent finding from twin studies is that the environment shared by family members does not contribute to the variation in susceptibility to asthma. At the same time, it is known that environmental risk factors that are shared by family members are associated with the liability for asthma. We hypothesize that the absence of a main effect of shared environmental factors in twin studies can be explained by gene–environment interaction, that is, that the effect of an environmental factor shared by family members depends on the genotype of the individual. We explore this hypothesis by modeling the resemblance in asthma liability in twin pairs as a function of various environmental risk factors and test for gene–environment interaction. Asthma data were obtained by parental report for nearly 12,000 5-year-old twin pairs. A series of environmental risk factors was examined: birth cohort, gestational age, time spent in incubator, breastfeeding, maternal educational level, maternal smoking during pregnancy, current smoking of parents, having older siblings, and amount of child care outside home. Results revealed that being a boy, born in the 1990s, premature birth, longer incubator time, and child care outside home increased the risk for asthma. With the exception of premature birth, however, none of these factors modified the genetic effects on asthma. In very premature children shared environmental influences were important. In children born after a gestation of 32 weeks or more only genetic factors were important to explain familial resemblance for asthma.

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