Evidence Of Gene-environment Interaction Research Articles

Evidence for gene-environment interactions in a linkage study of asthma and smoking exposure

Background: Asthma, a common and chronic disease of the airways, has a multifactorial cause involving both genetic and environmental factors. As a result, mapping genes that influence asthma susceptibility has been challenging. Objective: This study tests the hypothesis that inclusion of exposure to environmental tobacco smoke (ETS), a potential risk factor for asthma, would improve the ability to map genes for asthma. Methods: By using 144 white families from the Collaborative Study for the Genetics of Asthma, environmental information about exposure to ETS during infancy was incorporated into a genome-wide multipoint linkage analysis. Statistical significance of observed gene-environment interactions was assessed by means of simulation. Results: Three regions with nominal evidence for linkage when stratified on the basis of ETS exposure were identified ( P < .01) and showed a significant increase from the baseline lod score (1p at 97 cM, D1S1669-D1S1665; 5q at 135 cM, D5S1505-D5S816; and 9q at 106 cM, D9S910; all P < .05). In addition, 2 other regions, although not meeting nominal significance after stratification on the basis of ETS exposure, showed a significant increase from baseline lod score when ETS was taken into account (1q at 240 cM, D1S549; 17p at 3 cM, D17S1308; all P < .01). Conclusion: These results illustrate how evidence for linkage of asthma can depend on exposure to an environmental factor, such as ETS. Future linkage analyses should include information on suspected environmental factors for asthma to help target new candidate susceptibility genes for asthma.

COL9A3 gene polymorphism and obesity in intervertebral disc degeneration of the lumbar spine: evidence of gene-environment interaction.

Cross-sectional. To evaluate the interaction between the COL9A3 gene polymorphism and persistent obesity in relation to lumbar disc degeneration. Obesity has been suggested to be a risk factor for disc degeneration. There is some indication for an association between collagen IX genes and lumbar disc disease characterized by sciatica. However, the interaction between those factors in their influences on the risk of disc degeneration has not been studied. Blood samples from 135 middle-aged men who had undergone magnetic resonance imaging (MRI) of the lumbar spine were analyzed for the presence of an arginine to tryptophan change in the COL9A3 gene (Trp3 allele). The men represented three occupations: 41 were machine drivers, 42 were carpenters, and 52 were office workers. The discs L2/L3-L5/S1 were evaluated on MRI, using decreased signal intensity of the nucleus pulposus, posterior disc bulges, and decreased disc height as signs of disc degeneration. Based on self-reports on body height and weight currently and at the age of 25 years, obesity history was classified as no obesity, persistent obesity, and other. Rothman's synergy index was used as a measure of interaction between two factors. The Trp3 allele and persistent obesity acted synergistically to increase the risk of dark nucleus pulposus, posterior disc bulge, and decreased disc height at L4/L5; of multilevel posterior disc bulges; and of decreased disc height. From 45% to 71% of disc degeneration among persistently obese individuals with the Trp3 allele could be attributed to the synergism of these two factors. The effect of obesity on lumbar disc degeneration seems to be modified by the collagen IX gene polymorphism, so that people who carry the Trp3 allele are at increased risk if they are persistently obese.

Could stress cause psychosis in individuals vulnerable to schizophrenia?

It has long been considered that psychosocial stress plays a role in the expression of symptoms in schizophrenia (SZ), as it interacts with latent neural vulnerability that stems from genetic liability and early environmental insult. Advances in the understanding of the neurobiology of the stress cascade in both animal and human studies lead to a plausible model by which this interaction may occur: through neurotoxic effects on the hippocampus that may involve synaptic remodeling. Of late, the neurodevelopmental model of SZ etiology has been favored. But an elaboration of this schema that credits the impact of postnatal events and considers a role for neurodegenerative changes may be more plausible, given the evidence for gene-environment interaction in SZ expression and progressive structural changes observed with magnetic resonance imaging. Furthermore, new insights into nongliotic neurotoxic effects such as apoptosis, failure of neurogenesis, and changes in circuitry lead to an expansion of the time frame in which environmental effects may mediate expression of SZ symptoms.

Genetic Susceptibility to Benzene and Shortened Gestation: Evidence of Gene-Environment Interaction

This study investigated whether the association between low level benzene exposure and shortened gestation is modified by two susceptibility genes, CYP1A1 and GSTT1. This report includes 542 (302 nonexposed, 240 benzene-exposed) nonsmoking and nondrinking mothers of singleton live births at Beijing Yanshan Petrochemical Corporation between June 1995 and June 1997. Epidemiologic and clinical data and blood samples were obtained from mothers. Multiple linear regression models were used to estimate the associations of benzene exposure and genetic susceptibility with gestational age, adjusting for maternal age, education, parity, stress, passive smoking, prepregnancy weight and height, and infant's sex. Without consideration of genotype, benzene exposure was associated with a decrease in mean gestational age of 0.29 (standard error (SE), 0.12) week. When stratified by the maternal CYP1A1 genotype, the estimated decrease was 0.54 (SE, 0.12) week for the AA group, which was significantly greater (p = 0.003) than that for the Aa/aa group, which showed no decrease in gestational age. When both CYP1A1 and GSTT1 were considered, the greatest decrease was found among exposed mothers with the CYP1A1 AA-GSTT1 absent group (0.79 (SE, 0.25) week) and the CYP1A1 AA-GSTT1 present group (0.50 (SE, 0.22) week). Among the nonexposed, genetic susceptibility alone did not confer a significant adverse effect. This study provides evidence of gene-environment interaction and supports further assessment of the role of genetic susceptibility in the evaluation of reproductive toxins.

Parenting and child behavioral adjustment in early childhood: a quantitative genetic approach to studying family processes.

The aim of this study was to examine environmental and gene-environment processes linking parenting (i.e., affect, control, responsiveness) and preschool children's behavioral adjustment difficulties (e.g., noncompliance, conduct problems) by using bivariate genetic analyses of parents' and observers' ratings. The sample included 120 identical and same-sex fraternal twin pairs (M age = 43 months). Data sources included in-home observations, interviews, and parents' reports. Observers' ratings of children's difficult behaviors included shared and nonshared environmental variance. In contrast, parents' ratings of children's conduct problems showed genetic and nonshared environmental variance. Observer-rated maternal behavior included shared and nonshared environmental variance, although maternal responsiveness also included child genetic variance. Parent self-reported negative and positive affect included shared and nonshared environment as well as child genetic variance. There was no evidence for gene-environment interaction or dominance. Higher levels of difficult behavior and conduct problems covaried with higher levels of maternal negative affect and control and lower levels of maternal positive affect and control. Shared environmental mediation of these correlations was found for observations, whereas genetic and nonshared environmental mediation was found for parents' ratings. In general, estimates of shared environmental variance and mediation were greatest for observational data, and estimates of child genetic variance and mediation were greatest for parent-rated data. The implications of this pattern of findings for genetic research on family processes are discussed.

Evidence of gene-environment interaction in development of tuberculosis

Evidence of gene-environment interaction in development of tuberculosis

Serum-triglycerides and coagulation factor VII in elderly people; evidence for gene-environment interaction: L. I. Mennen, E. G. Schouten, C. Kluft, D. E. Grobbee, Department of Epidemiology and Public Health, Agricultural University Wageningen, The Netherlands, Gaubius Laboratory TNO-PG, Leiden, The Netherlands

Serum-triglycerides and coagulation factor VII in elderly people; evidence for gene-environment interaction: L. I. Mennen, E. G. Schouten, C. Kluft, D. E. Grobbee, Department of Epidemiology and Public Health, Agricultural University Wageningen, The Netherlands, Gaubius Laboratory TNO-PG, Leiden, The Netherlands

Interpersonal variables in the prediction of alcoholism among adoptees: evidence for gene-environment interactions.

The contributions of genetic and both positive and negative environmental factors were tested in the prediction of alcohol abuse/dependence among 300 adult adoptees. No direct effects for either genetic or environmental factors were significant in the prediction of adoptee alcohol abuse/dependence. However, among women, early-life family conflict and psychopathology in the adoptive family interacted with a biological background of alcoholism. Among women with at least one alcoholic biological parent, conflict or psychopathology in the adoptive family increased the probability of alcohol abuse and/or dependence. Among men, no significant interactions were found between a biological background of alcoholism and environmental variables. Results suggest a pattern of gene-environment interaction among women.

Evidence for gene-environment interaction in the development of adolescent antisocial behavior.

Data from three adoption studies are used to test for gene-environment interaction in the development of adolescent antisocial behaviors. Results indicate significant increases in antisocial behaviors when an adoptee has both a genetic factor and an adverse environmental factor present. The increase in number of antisocial behaviors due to both genetic and environmental factors acting together is far greater than the predicted increase from either factor acting alone.

The lack of evidence for co-adaptation in crosses between geographical races ofDrosophila subobscuraColl.

1. The paper described an attempt to see whether differences in co-adaptation between populations ofDrosophila subobscuraare related to the distance between them. The mean and the variance of body-size, development time and survival were recorded on parent populations and the F1and F2of various crosses to test for heterosis in the F1and decline in performance or greater variance in the F2, which might indicate the break-up of co-adapted gene arrays. Comparisons were carried out at different temperatures and on a variety of larval diets, especially sub-optimal ones in which the larvae were grown on synthetic media. A large number of wild flies were caught at sites separated by about 10 miles along a transect of southern Scotland; these comprised one series of comparisons. For more distant crosses flies were caught at sites in southern England, Denmark, Switzerland and Israel.2. There were well-defined differences in body-size, and, to a lesser degree, development time between populations from more widely separated localities and these showed evidence of a cline, northern populations having larger body-size. The difference in size between the Scottish and Isreal populations is about 20%.3. There was no evidence of differences in co-adaptation between populations even in crosses between populations from sites as far apart as Scotland and Israel. The F1's were always close to the mid-parent values and there was no evidence of breakdown in the F2nor of increased variability.4. There was hardly any evidence of gene-environment interaction either with respect to different diets or to different temperatures.5. Records of body-size on flies caught in the wild showed that they are extremely variable, indicating great variation in larval nutrition. Under natural condition stability of growth in body-size is conspicuously lacking in this species.6. An additional test of co-adaptation was based on the between-family variance of abdominal bristle number of intra- and inter-population matings in the two most widely separated populations. There was no evidence of greater variance in the inter-population series.7. To test for possible differences in breeding structure, the response to inbreeding was determined for two widely separated populations ofD. subobscuraand a long-established cage population ofD. melanogaster, on an unrestricted larval diet and also on several different kinds of sub-optimal diets. There was little or no sign of consistent differences between the species in their response to inbreeding.8. This test revealed differences between the two species in their minimum requirements for particular nutrients.subobscurais less able thanmelanogasterto withstand lower levels of protein and survival is particularly reduced. On the other hand,melanogasterhas a considerably higher requirement for choline. Where there are apparent differences between the species in the average effect of inbreeding, the inbreeding effect is greater on the relatively more sub-optimal diet.9. Comparison of the performance of the immediate descendants of wild flies with those derived from the same site, but kept in the laboratory for some twenty generations, failed to show any differences on several different diets and so there was no evidence that adaptation to laboratory conditions was important.10. The lack of evidence for co-adaptation apparently conflicts with what has been claimed for other species. Such differences are discussed.

The ecological genetics of growth inDrosophilaV. Gene-environment interaction and inbreeding

1. The growth of a number of inbred lines from the Pacific cage population have been compared under different conditions of temperature and nutrition. Body size and duration of the larval period were taken as measures of performance. Sub-optimal diets were provided by growing larvae on chemically defined synthetic media.2. Gene-environment interaction is widespread and often very great. The phenotypic effects of inbreeding on body size, even on a live yeast medium, may be greatly influenced by temperature. In one set of comparisons, inbred lines averaged 20% smaller at 25° C. but only 3% smaller at 18° C.3. Sub-optimal diets of different chemical composition, which lead to about the same average decline in body size, may differ greatly in the level of heterogeneity of response among the same set of inbred lines. Thus much greater heterogeneity was found on diets deficient in RNA than on diets with low protein levels. Such information is a useful guide to further study of gene-environment interaction in the outbred population.4. Diets which lead to a decline in body size of flies of the foundation population do not necessarily cause greater proportional decline on the part of inbred lines. Individual lines have been encountered in which body size is quite unaffected by changes in diet which reduce the size of the outbred flies by 25% or more.5. A series of crosses between lines from the same foundation population showed a striking level of homeostasis. The average body size and development time of the F1's was close to that of the population of flies on the favourable and two alternative sub-optimal diets. Also, compared with the parent lines, there was little evidence of gene-environment interaction among the crosses.

The ecological genetics of growth inDrosophila1. Body size and developmental time on different diets 1. Body size and developmental time on different diets

1. The interrelations between environment and the phenotypic expression of genetic differences have not received the attention they merit. Laboratory studies in quantitative inheritance, either by choice of character or experimental conditions, have not shed much light on this problem. Selection for the same character in different environments is likely to involve qualitative differences in physiology and development. Comparative study of such changes will throw light on the genetics of development generally, which in turn is relevant to how far the selection response can be pushed in a given direction. Since statistical variation between individuals must ultimately be interpreted in biological terms, the unnatural barriers between quantitative and physiological genetics must be broken down to clear the way for a greater variety of experimental analysis and a more widely based approach to the interpretation of individual differences in populations. The ecology of the animal provides the point of departure and guide to the kind of environmental variation which should be studied first. Since the suggested approach cuts across the conventional limits of quantitative, physiological and population genetics and exploits the concepts and methods of these alternative approaches to a common end, it is convenient to have a descriptive label. The term ‘ecological genetics’ has been adopted.2. This introductory paper is the first of a series dealing with experiments orientated along these lines. Since environmental variation largely consists of variation in the quantity and composition of the diet, the growth of individuals from a cage population ofDrosophila melanogasterand also other strains has been studied on a variety of aseptic, synthetic diets. Body size and duration of the larval period are taken as measures of growth. There is a well-marked ability to regulate body size, by extending the duration of development, provided the diet is not too deficient. When the diet is further reduced development time is further lengthened and body size is reduced as well.3. To test for genetic differences in reaction to the diet, strains have been created by selecting for large or small body size, and their performance, together with that of the cross between them, has been compared with the performance of unselected individuals on alternative diets for the first few generations of mass selection. There is evidence of gene-environment interaction quite early in selection, and after six generations striking differences were detected. It is concluded that genetic differences in reaction to different sub-optimal diets are widespread in the population.4. The within-culture variance is increased by growing larvae on progressively more deficient diets and is approximately twice as great on a low-protein diet as on the usual live yeast medium. This increase is attributed to the segregation of genetic differences which are unimportant and contribute little to the variance under more favourable conditions.5. Comparison of body size and development time in repeated tests with two diets lacking fructose or deficient in ribonucleic acid revealed evidence of a plasticity of response to minor nutritional variation which is characterized by a positive association between body size and the duration of the growth period. This relationship is the reverse of that associated with crude variation in the diet which leads to a negative association between development time and body size. This plasticity of response probably represents an aspect of physiological homeostasis. Genetic differences in the magnitude and direction of this response probably contribute to gene-environment interaction generally, and this probably accounts for apparent discrepancies in alternative estimates of the response to selection for large and small body size when these are based on deviations from the unselected. This suggests the need for determining how far body size may be increased either by altering the growth rate or by extending the growth period, and also how far strains differentiated in such respects differ in their reaction to controlled differences in nutrition.