An integrated phenomic approach to multivariate allelic association

The increased feasibility of genome-wide association has resulted in association becoming the primary method used to localize genetic variants that cause phenotypic variation. Much attention has been focused on the vast multiple testing problems arising from analyzing large numbers of single nucleotide polymorphisms. However, the inflation of experiment-wise type I error rates through testing numerous phenotypes has received less attention. Multivariate analyses can be used to detect both pleiotropic effects that influence a latent common factor, and monotropic effects that operate at a variable-specific levels, whilst controlling for non-independence between phenotypes. In this study, we present a maximum likelihood approach, which combines both latent and variable-specific tests and which may be used with either individual or family data. Simulation results indicate that in the presence of factor-level association, the combined multivariate (CMV) analysis approach performs well with a minimal loss of power as compared with a univariate analysis of a factor or sum score (SS). As the deviation between the pattern of allelic effects and the factor loadings increases, the power of univariate analyses of both factor and SSs decreases dramatically, whereas the power of the CMV approach is maintained. We show the utility of the approach by examining the association between dopamine receptor D2 TaqIA and the initiation of marijuana, tranquilizers and stimulants in data from the Add Health Study. Perl scripts that takes ped and dat files as input and produces Mx scripts and data for running the CMV approach can be downloaded from www.vipbg.vcu.edu/~sarahme/WriteMx

Evaluation of the Health Resources and Services Administration (HRSA) Behavioral Health Workforce and Education Training (BHWET) Grant

Our poster focuses on expanding the number of MS social work and MEd school counseling graduate students working with persons across the lifespan in vulnerable and medically underserved populations, providing evidence-based behavioral health services. In order to prepare the selected students, Interprofessional Education trainings and a 3-credit IPE academic course were administered, and data gathered and analyzed. The purpose of this research is to evaluate the effectiveness of the trainings and IPE academic courses. For the purpose of the IPE Integrated Care Trainings, pre-post test data were collected. In addition, open-ended questions were added to the post-test to ascertain additional feedback to improve the trainings and assess effectiveness. Pre-post test data were also collected for the 3-credit IPE academic course, in addition to open-ended questions, conducted after the completion of the IPE course to gain feedback. Chi-Square analyses were run for the quantitative data and themes were pulled from the open-ended questions. This presentation will focus on data outcomes from Year 3 of the four-year HRSA grant. In year three, data has been collected and analyzed from two IPE Integrated Care Trainings and two IPE academic courses, thus far. Participants for the trainings include HRSA-stipend students, field/faculty supervisors, and community members. In the first training of Year 3, N= 66. In the second training of Year 3, N= 95. In the two IPE academic courses, N=39. It was hypothesized that student pre/post data values are more likely to be significant, as compared to field/faculty supervisors, which has been proven true

The Associations between Asymmetries in Quadriceps Strength and Gait in Unilateral Transtibial Amputees

Background – Individuals with unilateral transtibial amputations (ITTAs) are asymmetrical in quadriceps strength. It is unknown if this is associated with gait performance characteristics such as walking speed and limb symmetry. Research Question – Are quadriceps strength asymmetries related to walking speed and/ or gait asymmetries in ITTAs?Methods – Knee-extensor isometric maximum voluntary torque (MVT) and rate of torque development (RTD) were measured in eight ITTAs. Gait data were captured as the ITTAs walked at self-selected habitual and fast speeds. Step length and single support time, peak knee extension moments and their impulse and peak vertical ground reaction force (vGRF) in the braking and propulsive phases of stance were extracted. Bilateral Asymmetry Index (BAI) and, for gait variables only, difference in BAI between walking speeds (ΔBAI) were calculated. Correlation analyses assessed the relationships between MVT and RTD asymmetry and (1) walking speed; (2) gait asymmetries.Results – Associations between strength and gait BAIs generally became more apparent at faster walking speeds, and when the difference in BAI between fast and habitual walking speed was considered. BAI RTD was strongly negatively correlated with habitual and fast walking speeds (r=~0.83). Larger BAI RTD was strongly correlated with propulsive vGRF BAI in fast walking, and larger ΔBAIs in vGRF during both the braking and propulsion phases of gait (r=0.74–0.92). ITTAs who exhibited greater BAI MVT showed greater ΔBAI in single support time (r=0.83). Significance – While MVT and RTD BAI appear to be associated with gait asymmetries in ITTAs, the magnitude of the asymmetry in RTD appears to be a more sensitive marker of walking speed. Based on these results, it’s possible that strengthening the knee-extensors of the amputated limb to improve both MVT and RTD symmetry may benefit walking speed, and reduce asymmetrical loading in gait.<br/

Extended twin study of alcohol use in Virginia and Australia

Drinking alcohol is a normal behavior in many societies, and prior studies have demonstrated it has both genetic and environmental sources of variation. Using two very large samples of twins and their first-degree relatives (Australia ≈ 20,000 individuals from 8,019 families; Virginia ≈ 23,000 from 6,042 families), we examine whether there are differences: (1) in the genetic and environmental factors that influence four interrelated drinking behaviors (quantity, frequency, age of initiation, and number of drinks in the last week), (2) between the twin-only design and the extended twin design, and (3) the Australian and Virginia samples. We find that while drinking behaviors are interrelated, there are substantial differences in the genetic and environmental architectures across phenotypes. Specifically, drinking quantity, frequency, and number of drinks in the past week have large broad genetic variance components, and smaller but significant environmental variance components, while age of onset is driven exclusively by environmental factors. Further, the twin-only design and the extended twin design come to similar conclusions regarding broad-sense heritability and environmental transmission, but the extended twin models provide a more nuanced perspective. Finally, we find a high level of similarity between the Australian and Virginian samples, especially for the genetic factors. The observed differences, when present, tend to be at the environmental level. Implications for the extended twin model and future directions are discussed

The effect of worrying on intolerance of uncertainty and positive and negative beliefs about worry

Background and Objectives: The effect of a worry manipulation on the clinical constructs intolerance of uncertainty (IU), negative beliefs about the consequences of worry (NCOW), positive beliefs about the consequences of worry (PCOW), in addition to the emotions anxiety and sadness, was examined. Methods: A non-clinical sample was split into two groups, a worry group (n = 29), who were asked to generate 20 potential worries about a hypothetical scenario, and a control group (n = 28), who were asked to generate 2 potential worries about the same scenario. Subsequently, participants were asked to complete measures of IU, NCOW, PCOW, sadness and anxiety. Results: The worry group scored significantly higher than the control group on measures of IU, NCOW and PCOW but not on measures of sadness and anxiety. Limitations: Possible limitations of the current study include the use of a student sample and the use of a hypothetical worry scenario. Conclusions: The results suggest that engaging in worry can increase scores on measures of the beliefs and thought patterns often used to causally explain worry. The results are in line with recent research showing bidirectionality between anxiety related symptoms and their associated clinical constructs, and are consistent with an approach which sees anxiety symptoms as part of an evolved integrated threat management system that alerts the individual to threats to goals or challenges, and coordinates cognitive, behavioral, and affective reactions to enable effective responding to these threats and challenges