Matching Items (11)
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- All Subjects: Genetics
- Creators: Lemery-Chalfant, Kathryn
Description
Fibromyalgia (FM) is a chronic musculoskeletal disorder characterized by widespread pain, fatigue, and a variety of other comorbid physiological and psychological characteristics, including a deficit of positive affect. Recently, the focus of research on the pathophysiology of FM has considered the role of a number of genomic variants. In the current manuscript, case-control analyses did not support the hypothesis that FM patients would differ from other chronic pain groups in catechol-O-methyltransferase (COMT) and mu-opioid receptor (OPRM1) genotype. However, evidence is provided in support of the hypothesis that functional single nucleotide polymorphisms on the COMT and OPRM1 genes would be associated with risk and resilience, respectively, in a dual processing model of pain-related positive affective regulation in FM. Forty-six female patients with a physician-confirmed diagnosis of FM completed an electronic diary that included once-daily assessments of positive affect and soft tissue pain. Multilevel modeling yielded a significant gene X environment interaction, such that individuals with met/met genotype on COMT experienced a greater decline in positive affect as daily pain increased than did either val/met or val/val individuals. A gene X environment interaction for OPRM1 also emerged, indicating that individuals with at least one asp allele were more resilient to elevations in daily pain than those homozygous for the asn allele. In sum, the findings offer researchers ample reason to further investigate the contribution of the catecholamine and opioid systems, and their associated genomic variants, to the still poorly understood experience of FM.
ContributorsFinan, Patrick Hamilton (Author) / Zautra, Alex (Thesis advisor) / Davis, Mary (Committee member) / Lemery-Chalfant, Kathryn (Committee member) / Presson, Clark (Committee member) / Arizona State University (Publisher)
Created2011
Description
Externalizing behaviors are pervasive, widespread, and disruptive across a multitude of settings and developmental contexts. While the conventional diathesis-stress model typically measures the disordered end of the spectrum, studies that span the range of behavior, from externalizing to competence behaviors, are necessary to see the full picture. To that end, this study examined the additive and nonadditive relations of a dimension of parenting (ranging from warm to rejecting), and variants in dopamine, vasopressin, and neuropeptide-y receptor genes on externalizing/competence in a large sample of predominantly Caucasian twin children in toddlerhood, middle childhood, and early adolescence. Variants within each gene were hypothesized to increase biological susceptibility to both negative and positive environments. Consistent with prediction, warmth related to lower externalizing/higher competence at all ages. Earlier levels of externalizing/competence washed out the effect of parental warmth on future externalizing/competence with the exception of father warmth in toddlerhood marginally predicting change in externalizing/competence from toddlerhood to middle childhood. Warmth was a significant moderator of the heritability of behavior in middle childhood and early adolescence such that behavior was less heritable (mother report) and more heritable (father report) in low warmth environments. Interactions with warmth and the dopamine and vasopressin genes in middle childhood and early adolescence emphasize the moderational role gene variants play in relations between the rearing environment and child behavior. For dopamine, the long variant related to increased sensitivity to parent warmth such that the children displayed more externalizing behaviors when exposed to rejection but they also displayed more competence behaviors when exposed to high warmth. Vasopressin moderation was only present under conditions of parental warmth, not rejection. Interactions with neuropeptide-y and warmth were not significant. The picture that emerges is one of gene-environment interplay, wherein the influence of both parenting and child genotype each depend on the level of the other. As genetic research moves forward, gene variants previously implicated as conferring risk for disorder should be reexamined in conjunction with salient aspects of the environment on the full range of the behavioral outcome of interest.
ContributorsO'Brien, T. Caitlin (Author) / Lemery-Chalfant, Kathryn (Thesis advisor) / Eisenberg, Nancy (Committee member) / Enders, Craig (Committee member) / Nagoshi, Craig (Committee member) / Arizona State University (Publisher)
Created2011
Description
The present study tested the factor structure of the externalizing disorders (e.g. attention-deficit hyperactivity disorder (ADHD), conduct disorder (SE), and substance experimentation (SE) ) in adolescence. In addition, this study tested the influence of the GABRA2 gene on the factors of the externalizing spectrum. Confirmatory factor analyses were used to test the factor structure of the externalizing spectrum. Specifically, three competing alternate confirmatory factor analytic models were tested: a one-factor model where all disorders loaded onto a single externalizing factor, a two-factor model where CD and SE loaded onto one factor and ADHD loaded onto another, and a three-factor model, where all three disorders loaded onto separate factors. Structural equation modeling was used to test the effect of a GABRA2 SNP, rs279858, on the factors of the externalizing spectrum. Analyses revealed that a three-factor model of externalizing disorders with correlated factors fit the data best. Additionally, GABRA2 had a significant effect on the SE factor in adolescence, but not on the CD or ADHD factors. These findings demonstrate that the externalizing disorders in adolescence share commonalities but also have separate sources of systematic variance. Furthermore, biological mechanisms may act as a unique etiological factor in the development of adolescent substance experimentation.
ContributorsWang, Frances L (Author) / Chassin, Laurie (Thesis advisor) / Lemery-Chalfant, Kathryn (Committee member) / Geiser, Christian (Committee member) / Arizona State University (Publisher)
Created2012
Description
This study examined whether early adversity at 30-months moderated the heritability of common and individual components of EF at 8 years. It was hypothesized that early adversity would not moderate the common EF factor, but instead moderate individual EF components. The sample included 208 twin pairs from the Arizona Twin Project. Early Adversity, assessed at 30 months of age, included Parenting Daily Hassles, low perceived MOS social support, punitive punishment (Parental Responses to Child Misbehavior), home chaos (Confusion, Hubbub, and Order Scale), CES-D maternal depression, and low maternal emotional availability. EF at 8 years included the Eriksen Flanker Task, Continuous Performance Task, Digit Span Forward and Backward, and parent-reported Attentional Focusing and Inhibitory Control (Temperament in Middle Childhood Questionnaire). For both early adversity and EF, the first principal components were extracted as composites. A confirmatory factor analysis was also conducted to index common EF. Genetic analyses were tested on the common EF composites as well as each individual task using umx. Univariate models revealed genetic influences on all individual measures and common EF, with broad sense heritability from .22 (Digit Span Backwards) to .61 (parent-reported inhibitory control). Shared environmental influences were found for the Flanker Task (.13) and parent-reported inhibitory control (.24), and E was moderate to high (.40-.73) for all measures except parent-report inhibitory control (.15) and attentional focusing (.31). Moderation of heritability was not observed in for Digit Span Forward, Digit Span Backward, and Attentional Focusing. However, the nonshared environment was moderated for Common EF, and the Flanker Task, and additive genes and the nonshared environment were moderated for the Continuous Performance Task and Inhibitory Control. Generally, total variance decreased as early adversity increased, suggesting that homes with low levels of adversity may allow children to interact with more proximal processes that can promote EF development.
ContributorsRea-Sandin, Gianna (Author) / Lemery-Chalfant, Kathryn (Thesis advisor) / Elam, Kit (Committee member) / Bradley, Robert (Committee member) / Arizona State University (Publisher)
Created2018
Description
This study focused on the connection between the EnvZ/OmpR two-component regulatory system and the iron homeostasis system in Escherichia coli, specifically how a mutant form of EnvZ11/OmpR is able to reduce the expression of fepA::lacZ, a reporter gene fusion in E. coli. FepA is one of several outer membrane siderophore receptors that allow extracellular siderophores bound to iron to enter the cells to power various biological processes. Previous studies have shown that in E. coli cells that expressed a mutant allele of envZ, called envZ11, which led to altered expression of various iron genes including down regulation of fepA::lacZ. The wild type EnvZ/OmpR system is not considered to regulate iron genes, but because these envz11 strains had downregulated fepA::lacZ, this study was undertaken to understand the connection and mechanisms of this downregulation. A large number of Lac+ revertants were obtained from the B32-2483 strain (envz11 and fepA::lacZ) and 7 Lac+ revertants that had reversion mutations not directly correcting the envZ11 allele were further characterized. With P1 phage transduction genetic mapping that involved moving a kanamycin resistance marker linked to fepA::lacZ, two Lac+ revertants were found to have their reversion mutations in the fepA promoter region, while the other five revertants had their mutations mapping outside the fepA region. These two revertants underwent DNA sequencing and found to carry two different single base pair mutations in two different locations of the fepA promoter region. Each one is in the Fur repressor binding region, but one also may have affected the Shine-Dalgarno region involved in translation initiation. All 7 reveratants underwent beta-galactosidase assays to measure fepA::lacZ expression. The two revertants that had mutations in the fepA promoter region had significantly increased fepA activity, with the revertant with the Shine-Dalgarno mutation having the most elevated fepA expression. The other 5 revertants that did not map in the fepA region had fepA expression elevated to the same level as that found in the wild type EnvZ/OmpR background. The data suggest that the negative effect of envZ11 can be overcome by multiple mechanisms, including directly correcting the envZ11 allele or changing the fepA promoter region.
ContributorsKalinkin, Victor Arkady (Co-author) / Misra, Rajeev (Co-author, Thesis director) / Mason, Hugh (Committee member) / Foy, Joseph (Committee member) / Biomedical Informatics Program (Contributor) / School of Life Sciences (Contributor) / W. P. Carey School of Business (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
The interaction between England and Scotland is complicated and continually changing. Scottish writer Sir Walter Scott examines this long-standing relationship through his various writings. Scott conveys a presence that is both acutely aware of the damages enacted upon Scotland by various English political efforts, and sensitive to the delicate relationship that the two regions had begun to form during his lifetime. Through a critical analysis of Scott's novel, Rob Roy, one can see the various strategies Scott used to balance the need to address prior controversies within the relationship, and the petition to move beyond the prior conflict and develop a mutual understanding of each culture. Through this, Scott is able to regenerate a sense of Scottish nationalism for his people, and encourage improved relations within the British Isles.
ContributorsChotena, Chelsea (Author) / Facinelli, Diane (Thesis director) / Foy, Joseph (Committee member) / White, Julianne (Committee member) / Barrett, The Honors College (Contributor)
Created2013-05
Description
Gle1 is an mRNP export mediator with major activity localized to the nuclear pore complex in eukaryotic cells. The protein's high preservation across vast phylogenetic distances allows us to approximate research on the properties of yeast Gle1 (yGle1) with those of human Gle1 (hGle1). Research at Vanderbilt University in 2016, which provides the research basis of this thesis, suggests that the coiled-coil domain of yGle1 is best crystallized in dicationic aqueous conditions of pH ~8.0 and 10\u201420% PEG 8000. Further exploration of crystallizable microconditions revealed a favorability toward lower pH and lower PEG concentration. Following the discovery of the protein's native crystallography conditions, a comprehensive meta-analysis of scientific literature on Gle1 was conducted on the association of Gle1 mutations with neuron disease.
ContributorsGaetano, Philip Pasquale (Author) / Foy, Joseph (Thesis director) / Dawson, T. Renee (Committee member) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
Description
The current study utilized data from two longitudinal samples to test mechanisms in the relation between a polygenic risk score indexing serotonin functioning and alcohol use in adolescence. Specifically, this study tested whether individuals with lower levels of serotonin functioning as indexed by a polygenic risk score were vulnerable to poorer self-regulation, and whether poorer self-regulation subsequently predicted the divergent outcomes of depressive symptoms and aggressive/antisocial behaviors. This study then examined whether depressive symptoms and aggressive/antisocial behaviors conferred risk for later alcohol use in adolescence, and whether polygenic risk and effortful control had direct effects on alcohol use that were not mediated through problem behaviors. Finally, the study examined the potential moderating role of gender in these pathways to alcohol use.
Structural equation modeling was used to test hypotheses. Results from an independent genome-wide association study of 5-hydroxyindoleacetic acid in the cerebrospinal fluid were used to create serotonin (5-HT) polygenic risk scores, wherein higher scores reflected lower levels of 5-HT functioning. Data from three time points were drawn from each sample, and all paths were prospective. Findings suggested that 5-HT polygenic risk did not predict self-regulatory constructs. However, 5-HT polygenic risk did predict the divergent outcomes of depression and aggression/antisociality, such that higher levels of 5-HT polygenic risk predicted greater levels of depression and aggression/antisociality. Results most clearly supported adolescents’ aggression/antisociality as a mechanism in the relation between 5-HT polygenic risk and later alcohol use. Deficits in self-regulation also predicted depression and aggression/antisociality, and indirectly predicted alcohol use through aggression/antisociality. These pathways to alcohol use might be the most salient for boys with low levels of socioeconomic status.
Results are novel contributions to the literature. The previously observed association between serotonin functioning and alcohol use might be due, in part, to the fact that individuals with lower levels of serotonin functioning are predisposed towards developing earlier aggression/antisociality. Results did not support the hypothesis that serotonin functioning predisposes individuals to deficits in self-regulatory abilities. Findings extend previous research by suggesting that serotonin functioning and self-regulation might be transdiagnostic risk factors for many types of psychopathology.
Structural equation modeling was used to test hypotheses. Results from an independent genome-wide association study of 5-hydroxyindoleacetic acid in the cerebrospinal fluid were used to create serotonin (5-HT) polygenic risk scores, wherein higher scores reflected lower levels of 5-HT functioning. Data from three time points were drawn from each sample, and all paths were prospective. Findings suggested that 5-HT polygenic risk did not predict self-regulatory constructs. However, 5-HT polygenic risk did predict the divergent outcomes of depression and aggression/antisociality, such that higher levels of 5-HT polygenic risk predicted greater levels of depression and aggression/antisociality. Results most clearly supported adolescents’ aggression/antisociality as a mechanism in the relation between 5-HT polygenic risk and later alcohol use. Deficits in self-regulation also predicted depression and aggression/antisociality, and indirectly predicted alcohol use through aggression/antisociality. These pathways to alcohol use might be the most salient for boys with low levels of socioeconomic status.
Results are novel contributions to the literature. The previously observed association between serotonin functioning and alcohol use might be due, in part, to the fact that individuals with lower levels of serotonin functioning are predisposed towards developing earlier aggression/antisociality. Results did not support the hypothesis that serotonin functioning predisposes individuals to deficits in self-regulatory abilities. Findings extend previous research by suggesting that serotonin functioning and self-regulation might be transdiagnostic risk factors for many types of psychopathology.
ContributorsWang, Frances Lynn (Author) / Chassin, Laurie (Thesis advisor) / Eisenberg, Nancy (Committee member) / Lemery-Chalfant, Kathryn (Committee member) / MacKinnon, David (Committee member) / Arizona State University (Publisher)
Created2017
Description
Pediatric chronic pain is pervasive and associated with myriad adverse consequences, yet due consideration has not been given to the mental health disturbances that often present alongside chronic pain and the etiological mechanisms that potentially underlie both. The current study examined the etiology underlying chronic pain and internalizing symptomology in middle childhood, considering both independent and co-occurring symptom presentations. Phenotypic parent-offspring associations across chronic pain and internalizing symptomology were also examined. Lastly, nuclear twin family models were tested to determine the extent to which genetic and environmental factors underlie parent-offspring transmission. The sample comprised 795 children (399 families; Mage= 9.7 years; SD = 0.92) and their parents drawn from the Arizona Twin Project. Results indicated that chronic pain was highly heritable (78%), whereas internalizing symptomology was modestly heritable (32%) and further subject to moderate shared environmental influence (50%). Moreover, 9% of the variance in chronic pain was explained by additive genetic factors shared with internalizing symptomology. Maternal chronic pain and internalizing symptomology were positively associated with both child chronic pain and internalizing symptomology. The association between maternal chronic pain and child chronic pain was more pronounced for girls than boys, whereas the association between maternal internalizing symptomology and child internalizing symptomology was more pronounced for boys than girls. Paternal chronic pain was not significantly associated with child chronic pain but was unexpectedly associated with lower child internalizing symptomology. The negative association between paternal chronic pain and child internalizing symptomology was more pronounced for boys than girls. Paternal internalizing symptomology was not significantly associated with child chronic pain but was positively associated with child internalizing symptomology. Lastly, the best fitting reduced nuclear twin family models for both chronic pain and internalizing symptomology retained additive genetic, sibling-specific shared environmental, and nonshared environmental parameters, where parent-offspring transmission was solely explained by shared genetics and sibling-specific shared environmental factors further accounted for co-twin resemblance. Results provide novel insight into common liabilities underlying chronic pain and internalizing symptomology in middle childhood, parent-offspring associations across chronic pain and internalizing symptomology, and the etiological mechanisms that explain symptom aggregation across generations.
ContributorsOro, Veronica (Author) / Lemery-Chalfant, Kathryn (Thesis advisor) / Chassin, Laurie (Committee member) / Davis, Mary (Committee member) / Su, Jinni (Committee member) / Arizona State University (Publisher)
Created2021
Description
It has been theorized that cultural variation within the family shapes children’s self-regulatory competence, yet there is a dearth of research examining the relation between culture and self-regulation. Family orientation refers to the emphasis on providing support, respect, and obligation to the family system, and is important for children’s functioning, yet existing literature on related constructs relies on parent-reported measures. Additionally, quantitative genetic research has neglected the role of culture in the genetic and environmental contributions on children’s self-regulation. There were three main aims of this study: 1) to propose novel coding schemes and factor analytic approaches to capture family orientation, 2) to examine the relation between family orientation and self-regulation in middle childhood, and 3) to examine whether family orientation moderates the genetic and environmental influences on self-regulation in middle childhood. The sample was drawn from the Arizona Twin Project (N=710) where children (49.1% female, 55.6% White, 28.3% Hispanic/Latino) were assessed at approximately eight years of age (Mage = 8.38 years, SD = 0.66). Family orientation values were indexed by parent-reported familism, whereas family orientation behaviors comprised coded measures of children’s family orientation and experimenter ratings of caregiver and child behavior. Outcome measures of self-regulation included the Continuous Performance Task, Flanker Task, Digit Span Backward, and parent- and teacher-reported effortful control (Temperament in Middle Childhood Questionnaire). Higher family orientation behaviors predicted positively predicted children’s self-regulation, with the exception of Digit Span Backward performance, and associations were not moderated by child sex, family SES, or race/ethnicity. Twin models revealed that differences in family orientation behaviors could be attributed to genetic, shared, and nonshared environmental influences, and additive genetic and nonshared environmental influences explained the variation across measures of self-regulation. Finally, there was no evidence that family orientation values nor behaviors moderated the genetic or environmental influences on children’s self-regulation. This study highlights the complex nature of cultural variation within the family and its importance for children’s self-regulatory abilities.
ContributorsRea-Sandin, Gianna (Author) / Lemery-Chalfant, Kathryn (Thesis advisor) / Doane, Leah D (Committee member) / Causadias, Jose (Committee member) / Grimm, Kevin J (Committee member) / Arizona State University (Publisher)
Created2022