Validation of PhenX measures in the personalized medicine research project for use in gene/environment studies.
ABSTRACT: BACKGROUND:The purpose of this paper is to describe the data collection efforts and validation of PhenX measures in the Personalized Medicine Research Project (PMRP) cohort. METHODS:Thirty-six measures were chosen from the PhenX Toolkit within the following domains: demographics; anthropometrics; alcohol, tobacco and other substances; cardiovascular; environmental exposures; cancer; psychiatric; neurology; and physical activity and physical fitness. Eligibility criteria for the current study included: living PMRP subjects with known addresses who consented to future contact and were not currently living in a nursing home, available GWAS data from eMERGE I for subjects where age-related cataract, HDL, dementia and resistant hypertension were the primary phenotypes, thus biasing the sample to the older PMRP participants. The questionnaires were mailed twice. Data from the PhenX measures were compared with information from PMRP questionnaires and data from Marshfield Clinic electronic medical records. RESULTS:Completed PhenX questionnaires were returned by 2271 subjects for a final response rate of 70%. The mean age reported on the PhenX questionnaire (73.1 years) was greater than the PMRP questionnaire (64.8 years) because the data were collected at different time points. The mean self-reported weight, and subsequently calculated BMI, were less on the PhenX survey than the measured values at the time of enrollment into PMRP (PhenX means 173.5 pounds and BMI 28.2 kg/m2 versus PMRP 182.9 pounds and BMI 29.6 kg/m2). There was 95.3% agreement between the two questionnaires about having ever smoked at least 100 cigarettes. 139 (6.2%) of subjects indicated on the PhenX questionnaire that they had been told they had a stroke. Of them, only 15 (10.8%) had no electronic indication of a prior stroke or TIA. All of the age-and gender-specific 95% confidence limits around point estimates for major depressive episodes overlap and show that 31% of women aged 50-64 reported symptoms associated with a major depressive episode. CONCLUSIONS:The approach employed resulted in a high response rate and valuable data for future gene/environment analyses. These results and high response rate highlight the utility of the PhenX Toolkit to collect valid phenotypic data that can be shared across groups to facilitate gene/environment studies.
Project description:BACKGROUND:The purpose of this manuscript is to describe the PhenX RISING network and the site experiences in the implementation of PhenX measures into ongoing population-based genomic studies. METHODS:Eighty PhenX measures were implemented across the seven PhenX RISING groups, thirty-three of which were used at more than two sites, allowing for cross-site collaboration. Each site used between four and 37 individual measures and five of the sites are validating the PhenX measures through comparison with other study measures. Self-administered and computer-based administration modes are being evaluated at several sites which required changes to the original PhenX Toolkit protocols. A network-wide data use agreement was developed to facilitate data sharing and collaboration. RESULTS:PhenX Toolkit measures have been collected for more than 17,000 participants across the PhenX RISING network. The process of implementation provided information that was used to improve the PhenX Toolkit. The Toolkit was revised to allow researchers to select self- or interviewer administration when creating the data collection worksheets and ranges of specimens necessary to run biological assays has been added to the Toolkit. CONCLUSIONS:The PhenX RISING network has demonstrated that the PhenX Toolkit measures can be implemented successfully in ongoing genomic studies. The next step will be to conduct gene/environment studies.
Project description:The PhenX Toolkit provides researchers with recommended, well-established, low-burden measures suitable for human subject research. The database of Genotypes and Phenotypes (dbGaP) is the data repository for a variety of studies funded by the National Institutes of Health, including genome-wide association studies. The dbGaP requires that investigators provide a data dictionary of study variables as part of the data submission process. Thus, dbGaP is a unique resource that can help investigators identify studies that share the same or similar variables. As a proof of concept, variables from 16 studies deposited in dbGaP were mapped to PhenX measures. Soon, investigators will be able to search dbGaP using PhenX variable identifiers and find comparable and related variables in these 16 studies. To enhance effective data exchange, PhenX measures, protocols, and variables were modeled in Logical Observation Identifiers Names and Codes (LOINC® ). PhenX domains and measures are also represented in the Cancer Data Standards Registry and Repository (caDSR). Associating PhenX measures with existing standards (LOINC® and caDSR) and mapping to dbGaP study variables extends the utility of these measures by revealing new opportunities for cross-study analysis.
Project description:OBJECTIVE:A Working Group (WG) of tobacco regulatory science experts identified measures for the tobacco environment domain. METHODS:This article describes the methods by which measures were identified, selected, approved and placed in the PhenX Toolkit. FINDINGS:The WG identified 20 initial elements relevant to tobacco regulatory science and determined whether they were already in the PhenX Toolkit or whether novel or improved measures existed. In addition to the 10 complementary measures already in the Toolkit, the WG recommended 13 additional measures: aided and confirmed awareness of televised antitobacco advertising, interpersonal communication about tobacco advertising, media use, perceived effectiveness of antitobacco advertising, exposure to smoking on television and in the movies, social norms about tobacco (for adults and for youth), worksite policies, youth cigarette purchase behaviours and experiences, compliance with cigarette packaging and labelling policies, local and state tobacco control public policies, and neighbourhood-level racial/ethnic composition. Supplemental measures included youth social capital and compliance with smoke-free air laws and with point of sale and internet tobacco marketing restrictions. Gaps were identified in the areas of policy environment (public and private), communications environment, community environment and social environment (ie, the norms/acceptability of tobacco use). CONCLUSIONS:Consistent use of these tobacco environment measures will enhance rigor and reproducability of tobacco research.
Project description:Investigating the association between biobank derived genomic data and the information of linked electronic health records (EHRs) is an emerging area of research for dissecting the architecture of complex human traits, where cases and controls for study are defined through the use of electronic phenotyping algorithms deployed in large EHR systems. For our study, 2580 cataract cases and 1367 controls were identified within the Marshfield Personalized Medicine Research Project (PMRP) Biobank and linked EHR, which is a member of the NHGRI-funded electronic Medical Records and Genomics (eMERGE) Network. Our goal was to explore potential gene-gene and gene-environment interactions within these data for 529,431 single nucleotide polymorphisms (SNPs) with minor allele frequency > 1%, in order to explore higher level associations with cataract risk beyond investigations of single SNP-phenotype associations. To build our SNP-SNP interaction models we utilized a prior-knowledge driven filtering method called Biofilter to minimize the multiple testing burden of exploring the vast array of interaction models possible from our extensive number of SNPs. Using the Biofilter, we developed 57,376 prior-knowledge directed SNP-SNP models to test for association with cataract status. We selected models that required 6 sources of external domain knowledge. We identified 5 statistically significant models with an interaction term with p-value < 0.05, as well as an overall model with p-value < 0.05 associated with cataract status. We also conducted gene-environment interaction analyses for all GWAS SNPs and a set of environmental factors from the PhenX Toolkit: smoking, UV exposure, and alcohol use; these environmental factors have been previously associated with the formation of cataracts. We found a total of 288 models that exhibit an interaction term with a p-value ? 1×10(-4) associated with cataract status. Our results show these approaches enable advanced searches for epistasis and gene-environment interactions beyond GWAS, and that the EHR based approach provides an additional source of data for seeking these advanced explanatory models of the etiology of complex disease/outcome such as cataracts.
Project description:Purpose:The co-existence of chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) has been described as the overlap syndrome. The objective of the study is to investigate the performance of Berlin Questionnaire (BQ), modified Berlin Questionnaire (MBQ), and STOP-Bang score in screening overlap syndrome from COPD subjects and investigate how pulmonary function interferes with questionnaire scoring. Subjects and Methods:Among 116 COPD subjects included in this study, 62 were overlap syndrome subjects and 54 were COPD subjects without OSA. Subjects included were asked to fill out the questionnaires to collect demographic characteristics of subjects and questionnaire scores of BQ, MBQ, and STOP-Bang; perform pulmonary function test to confirm their COPD diagnosis; and perform polysomnography. Results:AUC (area under the curve) of BQ, MBQ, and STOP-Bang score in screening OSA among patients with COPD was 0.71 (0.64-0.79), 0.75 (0.67-0.83), and 0.72 (0.64-0.80). In COPD subjects without OSA, FEV1%pred was statistically associated with the misdiagnosis of BQ (P= 0.0091), MBQ (P= 0.0143), and STOP-Bang (P= 0.0453). In patients with overlap syndrome, FVC%pred affected the risk of misdiagnosis of the three questionnaires (BQ: P= 0.0413; MBQ: P= 0.0150; STOP-Bang: P= 0.0241). BMI and neck circumferences (NC) were negatively correlated with FEV1%pred (BMI: P= 0.0454; NC: P= 0.0230) and FVC%pred (BMI: P= 0.0042; NC: P= 0.0367) in overlap subjects. In contrast, BMI was positively correlated with FEV1/FVC (P= 0.0141) and FEV1%pred (P= 0.0391) in COPD subjects without OSA. Conclusion:BQ, MBQ, and STOP-Bang score performed well in COPD subjects for screening OSA. The diagnosis of the three questionnaires was more accurate in subjects with lower FEV1%pred or FVC%pred value. Pulmonary function might exert influence on the diagnosis efficacy of the three questionnaires through BMI and neck circumference.
Project description:The need for comprehensive analysis to compare and combine data across multiple studies in order to validate and extend results is widely recognized. This paper aims to assess the extent of data compatibility in the substance abuse and addiction (SAA) sciences through an examination of measure commonality, defined as the use of similar measures, across grants funded by the National Institute on Drug Abuse (NIDA) and the National Institute on Alcohol Abuse and Alcoholism (NIAAA). Data were extracted from applications of funded, active grants involving human-subjects research in four scientific areas (epidemiology, prevention, services, and treatment) and six frequently assessed scientific domains. A total of 548 distinct measures were cited across 141 randomly sampled applications. Commonality, as assessed by density (range of 0-1) of shared measurement, was examined. Results showed that commonality was low and varied by domain/area. Commonality was most prominent for (1) diagnostic interviews (structured and semi-structured) for substance use disorders and psychopathology (density of 0.88), followed by (2) scales to assess dimensions of substance use problems and disorders (0.70), (3) scales to assess dimensions of affect and psychopathology (0.69), (4) measures of substance use quantity and frequency (0.62), (5) measures of personality traits (0.40), and (6) assessments of cognitive/neurologic ability (0.22). The areas of prevention (density of 0.41) and treatment (0.42) had greater commonality than epidemiology (0.36) and services (0.32). To address the lack of measure commonality, NIDA and its scientific partners recommend and provide common measures for SAA researchers within the PhenX Toolkit.
Project description:Forty seven healthy HK-Chinese subjects between ages 18-30 were recruited. Subjects need to pass the McMonnies Questionnaire prior to the data collection. Visual functions and anterior ocular health were first assessed. One hour later, the subjects’ tear osmolalities were tested by the TearLab Osmometer. Tear samples were then collected by disposable microcapillary tubes. TripleTOF 6600 Mass Spectrometer was used to analyze the tear protein components.
Project description:Polygonum multiflorum Radix (PMR) has long history in hair growth promotion and hair coloring in clinical applications. However, several crucial problems in its clinic usage and mechanisms are still unsolved or lack scientific evidences. In this research, C57BL/6J mice were used to investigate hair growth promotion activity and possible mechanism of PMR and Polygonum multiflorum Radix Preparata (PMRP). Hair growth promotion activities were investigated by hair length, hair covered skin ratio, the number of follicles, and hair color. Regulation effects of several cytokines involved in the hair growth procedure were tested, such as fibroblast growth factor (FGF-7), Sonic Hedgehog (SHH), ?-catenin, insulin-like growth factor-1 (IGF-1), and hepatocyte growth factor (HGF). Oral PMR groups had higher hair covered skin ratio (100 ± 0.00%) than oral PMRP groups (48%~88%). However, topical usage of PMRP had about 90% hair covered skin ratio. Both oral administration of PMR and topically given PMRP showed hair growth promotion activities. PMR was considered to be more suitable for oral administration, while PMRP showed greater effects in external use. The hair growth promotion effect of oral PMR was most probably mediated by the expression of FGF-7, while topical PMRP promoted hair growth by the stimulation of SHH expression.
Project description:<h4>Background</h4>Many neglected tropical diseases (NTDs) are not fatal, but they are disabling, disfiguring and stigmatizing. More accurate data on these aspects would benefit planning, monitoring and evaluation of interventions, as well as provision of appropriate services for the often life-long consequences. In 2015, a cross-NTD toolkit was developed, consisting of a variety of existing questionnaires to measure morbidity, disability and health-related quality of life. The toolkit covers the domains of the International Classification of Functioning, Disability and Health (ICF) framework. These tools have been developed in a source country, however, it was intended for the cross-NTD toolkit to be applicable across NTDs in many countries with different cultures and languages in order to generate universally comparative data. Therefore; the present study aimed to validate several tools of the toolkit among people affected by leprosy or leishmaniasis in the cultural settings of Cartagena and Cúcuta, Colombia.<h4>Methodology</h4>This study aimed to validate the following tools among 55 participants between 18-85 years old, affected by leprosy and leishmaniasis: (I) Clinical Profile, (II) Self-Reporting Questionnaire (SRQ), (III) WHO Quality of Life assessment-abbreviated version (WHOQOL-BREF), and (IV) WHO Quality of Life assessment-Disability (WHOQOL-DIS). The tools were administered during face-to-face interviews and were followed by open questions about the respondents' thoughts on format of the tool and the understanding, relevance and acceptability of the items. The tools were validated using a qualitative method approach based on the framework for cultural equivalence, measured by the cultural, item, semantic and operational equivalences.<h4>Results</h4>The Clinical Profile was seen as acceptable and relevant, only the semantic equivalence was not as satisfying and needs a few adaptations. The SRQ was very well understood and shows to reach the equivalences for the population of Colombia without any additional changes. Several items of the WHOQOL-BREF and the WHOQOL-DIS were not well understood and changes are recommended due to semantic difficulties. Operational equivalence of both questionnaires was not as desired in relation to the used response scales. The participants shared that the tools are relevant and important for their particular situation.<h4>Conclusions/significance</h4>The SRQ is found to be a valid tool for Colombia and can be included in the cross-NTD toolkit. The Clinical Profile, WHOQOL-BREF & WHOQOL-DIS need changes and retesting among Colombian people affected by an NTD. The toolkit as a whole is seen as useful to show the effects leprosy and leishmaniasis have on the participants. This cultural validation will contribute to a universally applicable cross-NTD toolkit.
Project description:OBJECTIVE:To determine if a 3-hour therapeutic neuroscience education session alters physical therapy student's knowledge of pain and effects their attitudes and beliefs regarding treating chronic pain. METHODS:Seventy-seven entry-level doctoral physical therapy students participated in the study. Following consent, demographic data were obtained and then the subjects completed the Neuroscience of Pain Questionnaire, the Health Care Provider's Pain and Impairment Relationship Scale and an additional questionnaire designed by the researchers. The subjects then received a 3-hour educational session developed by the researchers, focusing on the neurobiology and physiology of pain. The questionnaires were re-administered immediately after the educational session and at 6 months post-education. RESULTS:Seventy-seven subjects (mean age = 24.7 years, 57.1% female and 81.8% white) completed the questionnaires pre- and post-educational session with 75 completing the questionnaires at 6 months. To assess the effect of the education on the scores of the questionnaires, a repeated measures ANOVA was conducted. Students demonstrated significantly higher scores on the neuroscience of pain questionnaire (p < 0.001) with no significant effect found on the attitudes and beliefs questionnaire at any of the time points. There were significant differences found on some of the individual questions that were part of the additional questionnaire. DISCUSSION:An educational session on the neuroscience of pain is beneficial for educating entry-level doctoral physical therapy students immediately post-education and at 6 months. This educational session had no effect on the student's attitudes and beliefs regarding treating the chronic pain population. There were additional significant findings regarding individual questions posed to the subjects.