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1.
Patient Educ Couns ; 100(4): 748-759, 2017 04.
Article in English | MEDLINE | ID: mdl-27939846

ABSTRACT

OBJECTIVES: To assess advanced communication skills among second-year medical students exposed either to a computer simulation (MPathic-VR) featuring virtual humans, or to a multimedia computer-based learning module, and to understand each group's experiences and learning preferences. METHODS: A single-blinded, mixed methods, randomized, multisite trial compared MPathic-VR (N=210) to computer-based learning (N=211). Primary outcomes: communication scores during repeat interactions with MPathic-VR's intercultural and interprofessional communication scenarios and scores on a subsequent advanced communication skills objective structured clinical examination (OSCE). Multivariate analysis of variance was used to compare outcomes. SECONDARY OUTCOMES: student attitude surveys and qualitative assessments of their experiences with MPathic-VR or computer-based learning. RESULTS: MPathic-VR-trained students improved their intercultural and interprofessional communication performance between their first and second interactions with each scenario. They also achieved significantly higher composite scores on the OSCE than computer-based learning-trained students. Attitudes and experiences were more positive among students trained with MPathic-VR, who valued its providing immediate feedback, teaching nonverbal communication skills, and preparing them for emotion-charged patient encounters. CONCLUSIONS: MPathic-VR was effective in training advanced communication skills and in enabling knowledge transfer into a more realistic clinical situation. PRACTICE IMPLICATIONS: MPathic-VR's virtual human simulation offers an effective and engaging means of advanced communication training.


Subject(s)
Clinical Competence , Communication , Computer Simulation , Patient Simulation , Students, Medical/psychology , Adult , Curriculum , Education, Medical , Female , Humans , Male , Physician-Patient Relations , Single-Blind Method , User-Computer Interface
2.
J Occup Environ Med ; 58(12): 1223-1230, 2016 12.
Article in English | MEDLINE | ID: mdl-27930483

ABSTRACT

OBJECTIVE: In workplace settings, autonomy is implicated in employee motivation as well as supervisor autonomy support. As a profession of risk, firefighters may experience greater levels of stress. METHODS: A self-determination paradigm was applied to the firefighter workplace. Of particular interest were perceived competence (to perform job duties) and the experience of stress. Firefighters' levels of autonomous and controlled regulation were surveyed, along with their perceptions of the autonomy support of their immediate supervisor. RESULTS: Autonomous regulation was positively related to perceived competence, whereas controlled regulation was negatively related. Higher levels of controlled regulation were also connected with greater stress. In contrast, greater perceived autonomy support was associated with decreased stress. CONCLUSIONS: Both perceived competence and stress are related to firefighter motivation and autonomy support. Recommendations are offered to increase autonomy support by chief officers.


Subject(s)
Firefighters/psychology , Personal Autonomy , Professional Competence , Stress, Psychological/epidemiology , Adult , Female , Humans , Male , Middle Aged , Motivation , Surveys and Questionnaires , Young Adult
3.
Stress Health ; 32(5): 551-558, 2016 Dec.
Article in English | MEDLINE | ID: mdl-26620490

ABSTRACT

The present study examined the importance of time allocation, pressure and support variables together as determinants of faculty burnout. Using a large sample of university faculty (N = 1439), we were able to show that time allocation variables and perceived pressure contribute to faculty burnout. As expected, decreased social support, family, sleep and leisure time were related to higher levels of burnout. Grantsmanship and service activities appeared as the most critical factors associated with faculty burnout. Faculty burnout is an important topic, and the insights provided here help offer some directions for future research as well as the development of effective institutional policies. Copyright © 2015 John Wiley & Sons, Ltd.


Subject(s)
Burnout, Professional/psychology , Faculty/psychology , Social Support , Adult , Education, Graduate , Female , Humans , Male , Middle Aged , Universities
4.
Educ Psychol Meas ; 76(3): 436-453, 2016 Jun.
Article in English | MEDLINE | ID: mdl-29795872

ABSTRACT

Coefficient omega and alpha are both measures of the composite reliability for a set of items. Unlike coefficient alpha, coefficient omega remains unbiased with congeneric items with uncorrelated errors. Despite this ability, coefficient omega is not as widely used and cited in the literature as coefficient alpha. Reasons for coefficient omega's underutilization include a limited knowledge of its statistical properties. However, consistent efforts to understand the statistical properties of coefficient omega can help improve its utilization in research efforts. Here, six approaches for estimating confidence intervals for coefficient omega with unidimensional congeneric items were evaluated through a Monte Carlo simulation. The evaluations were made through simulation conditions that mimic realistic conditions that investigators are likely to face in applied work, including items that are not normally distributed and small sample size(s). Overall, the normal theory bootstrap confidence interval had the best performance across all simulation conditions that included sample sizes less than 100. However, most methods had sound coverage with sample sizes of 100 or more.

5.
Violence Against Women ; 21(8): 917-38, 2015 Aug.
Article in English | MEDLINE | ID: mdl-26062874

ABSTRACT

This study examined the relationship between emotional distress (defined as depression, brooding, and negative affect), alcohol outcomes, and bidirectional intimate partner violence among lesbian women. Results lend support to the self-medication hypothesis, which predicts that lesbian women who experience more emotional distress are more likely to drink to cope, and in turn report more alcohol use, problem drinking, and alcohol-related problems. These alcohol outcomes were, in turn, associated with bidirectional partner violence (BPV). These results offer preliminary evidence that, similar to findings for heterosexual women, emotional distress, alcohol use, and particularly, alcohol-related problems are risk factors for BPV among lesbian women.


Subject(s)
Alcohol Drinking , Alcohol-Related Disorders/complications , Depression/complications , Domestic Violence , Homosexuality, Female , Intimate Partner Violence , Stress, Psychological/complications , Adaptation, Psychological , Adolescent , Adult , Affect , Alcoholism/complications , Ethanol , Female , Humans , Risk Factors , Sexual Partners , Spouse Abuse , Young Adult
6.
Violence Vict ; 29(5): 784-96, 2014.
Article in English | MEDLINE | ID: mdl-25905128

ABSTRACT

This study examined alcohol consumption, internalized homophobia, and outness as related to men's (N = 107) reports of the perpetration of violence against a same-sex partner. Higher typical weekly alcohol consumption, higher levels of internalized homophobia, and less outness (e.g., lower levels of disclosure of one's sexual orientation) predicted the perpetration of partner violence. In contrast to what we expected, the interaction between higher alcohol consumption and higher levels of outness about one's sexual orientation (i.e., being open to friends, family members, work colleagues) increased the likelihood of participants' reports of perpetrating physical violence. These results suggest the importance of both alcohol consumption and sexual minority stressors and their interactions in understanding men's perpetration of same-sex partner violence.


Subject(s)
Alcohol Drinking/epidemiology , Homosexuality, Male/psychology , Homosexuality, Male/statistics & numerical data , Sexual Partners/psychology , Spouse Abuse/psychology , Spouse Abuse/statistics & numerical data , Adult , Aged , Humans , Interpersonal Relations , Logistic Models , Male , Middle Aged , Risk-Taking , Surveys and Questionnaires , Young Adult
7.
Am J Manag Care ; 18(4): 201-6, 2012 04.
Article in English | MEDLINE | ID: mdl-22554008

ABSTRACT

OBJECTIVES: To predict adoption (80% rate of use) of an electronic health record (EHR) by admitting physicians using a heuristic model. METHODS: Administrative data collected for 326 physicians who admitted at least 10 patients to 3 hospitals during the 6 months following EHR activation represented more than 80% of the total admissions. Functions evaluated included computerized physician order entry (CPOE), electronic history and physical (EH and P), and electronic discharge summary (EDS). Independent variables included hospital size, physician alignment, physician group size, use of an office EHR, age, sex, specialty, volume, hospital based, inpatient to outpatient ratio, and loyalty. RESULTS: CPOE adoption was more likely (P <.01) for physicians who were employed, male, and had a high inpatient ratio, a lower patient volume, and a community hospital setting. EH and P and EDS adoption were more likely for physicians with financial alignment and a large academic hospital setting. CONCLUSIONS: Personal factors (loyalty, age, sex) were generally not predictive. Organizational factors (hospital setting, financial alignment) were most predictive of adoption. Study results may help administrators improve EHR installations.


Subject(s)
Electronic Health Records/statistics & numerical data , Physicians/statistics & numerical data , Age Factors , Delivery of Health Care, Integrated , Female , Forecasting , Hospitals, Community/statistics & numerical data , Humans , Male , Patient Admission , Retrospective Studies , Sex Factors , Virginia
8.
Appl Psychol Health Well Being ; 4(2): 202-17, 2012 Jul.
Article in English | MEDLINE | ID: mdl-26286978

ABSTRACT

BACKGROUND: Self-determination theory has been widely applied to understanding individuals' health-related behaviors such as eating healthy foods and exercising. Different reasons for engagement are associated with varying levels of personal agency or autonomy. Authority figures in the environment can be supportive of autonomy or, in contrast, controlling. Although researchers have assessed individuals' perceptions of the autonomy-support in their environments, studies have not directly examined the authority figures' orientations to autonomy with respect to health contexts. METHODS: A new scale, Parent Orientations to Health, was created to investigate parent orientation to autonomy and control with respect to healthy eating and exercise in children. One hundred and forty-three parents of elementary school-aged children responded to the scale. RESULTS: Scale validation and reliability results indicate that the scale successfully assessed parent orientation towards autonomy for children in health contexts. Furthermore, parent autonomy orientation varied according to child weight status and the healthiness of the child's diet. CONCLUSIONS: Parent orientation towards autonomy can be evaluated through the use of the Parent Orientations to Health scale. In addition, parent autonomy orientation is associated with both the healthiness of the child's diet (as perceived by the parent) and the child's body mass index.


Subject(s)
Diet/psychology , Exercise/psychology , Health Behavior , Parents/psychology , Personal Autonomy , Adult , Attitude to Health , Child , Eating/psychology , Female , Humans , Male , Middle Aged , Motivation , Parent-Child Relations
9.
BMC Genet ; 12: 28, 2011 Mar 04.
Article in English | MEDLINE | ID: mdl-21375750

ABSTRACT

BACKGROUND: Questions remain regarding the utility of self-reported ethnicity (SRE) in genetic and epidemiologic research. It is not clear whether conditioning on SRE provides adequate protection from inflated type I error rates due to population stratification and admixture. We address this question using data obtained from the Multi-Ethnic Study of Atherosclerosis (MESA), which enrolled individuals from 4 self-reported ethnic groups. We compare the agreement between SRE and genetic based measures of ancestry (GBMA), and conduct simulation studies based on observed MESA data to evaluate the performance of each measure under various conditions. RESULTS: Four clusters are identified using 96 ancestry informative markers. Three of these clusters are well delineated, but 30% of the self-reported Hispanic-Americans are misclassified. We also found that MESA SRE provides type I error rates that are consistent with the nominal levels. More extensive simulations revealed that this finding is likely due to the multi-ethnic nature of the MESA. Finally, we describe situations where SRE may perform as well as a GBMA in controlling the effect of population stratification and admixture in association tests. CONCLUSIONS: The performance of SRE as a control variable in genetic association tests is more nuanced than previously thought, and may have more value than it is currently credited with, especially when smaller replication studies are being considered in multi-ethnic samples.


Subject(s)
Atherosclerosis/ethnology , Atherosclerosis/genetics , Ethnicity/genetics , Racial Groups/genetics , Computer Simulation , Genetic Association Studies , Hispanic or Latino/genetics , Humans , Hypertrophy, Left Ventricular/ethnology , Hypertrophy, Left Ventricular/genetics , Self Report
10.
Arthritis Rheum ; 62(12): 3547-53, 2010 Dec.
Article in English | MEDLINE | ID: mdl-21120996

ABSTRACT

OBJECTIVE: Large-scale genetic association studies have identified >20 rheumatoid arthritis (RA) risk alleles among individuals of European ancestry. The influence of these risk alleles has not been comprehensively studied in African Americans. We therefore sought to examine whether these validated RA risk alleles are associated with RA risk in an African American population. METHODS: Twenty-seven candidate single-nucleotide polymorphisms (SNPs) were genotyped in 556 autoantibody-positive African Americans with RA and 791 healthy African American control subjects. Odds ratios (ORs) and 95% confidence intervals (95% CIs) for each SNP were compared with previously published ORs for RA patients of European ancestry. We then calculated a composite genetic risk score (GRS) for each individual based on the sum of all risk alleles. RESULTS: Overlap of the ORs and 95% CIs between the European and African American populations was observed for 24 of the 27 candidate SNPs. Conversely, 3 of the 27 SNPs (CCR6 rs3093023, TAGAP rs394581, and TNFAIP3 rs6920220) demonstrated ORs in the opposite direction from those reported for RA patients of European ancestry. The GRS analysis indicated a small but highly significant probability that African American patients relative to control subjects were enriched for the risk alleles validated in European RA patients (P = 0.00005). CONCLUSION: The majority of RA risk alleles previously validated for RA patients of European ancestry showed similar ORs in our population of African Americans with RA. Furthermore, the aggregate GRS supports the hypothesis that these SNPs are risk alleles for RA in the African American population. Future large-scale genetic studies are needed to validate these risk alleles and identify novel RA risk alleles in African Americans.


Subject(s)
Arthritis, Rheumatoid/genetics , Black or African American/genetics , Polymorphism, Single Nucleotide/genetics , White People/genetics , Adult , Black or African American/ethnology , Alleles , Arthritis, Rheumatoid/ethnology , Case-Control Studies , DNA-Binding Proteins , Female , Genotype , Humans , Intracellular Signaling Peptides and Proteins/genetics , Male , Middle Aged , Nuclear Proteins/genetics , Odds Ratio , Receptors, CCR6/genetics , Risk Factors , Tumor Necrosis Factor alpha-Induced Protein 3 , White People/ethnology
11.
Int J Environ Res Public Health ; 7(9): 3332-47, 2010 09.
Article in English | MEDLINE | ID: mdl-20948927

ABSTRACT

It is conceivable that toxic metals contribute to obesity by influencing various aspects of metabolism, such as by substituting for essential micronutrients and vital metals, or by inducing oxidative stress. Deficiency of the essential metal zinc decreases adiposity in humans and rodent models, whereas deficiencies of chromium, copper, iron, and magnesium increases adiposity. This study utilized the NHANES 99-02 data to explore the association between waist circumference and body mass index with the body burdens of selected toxic metals (barium, cadmium, cobalt, cesium, molybdenum, lead, antimony, thallium, and tungsten). Some of the associations were significant direct relationships (barium and thallium), and some of the associations were significant inverse relationships (cadmium, cobalt, cesium, and lead). Molybdenum, antimony, and tungsten had mostly insignificant associations with waist circumference and body mass index. This is novel result for most of the toxic metals studied, and a surprising result for lead because high stored lead levels have been shown to correlate with higher rates of diabetes, and obesity may be a key risk factor for developing diabetes. These associations suggest the possibility that environmental exposure to metals may contribute to variations in human weight gain/loss. Future research, such as prospective studies rather than the cross-sectional studies presented here, is warranted to confirm these findings.


Subject(s)
Metals/urine , Obesity/epidemiology , Adolescent , Adult , Body Burden , Body Mass Index , Child , Child, Preschool , Cross-Sectional Studies , Environmental Exposure , Female , Humans , Male , Metals/toxicity , Middle Aged , Nutrition Surveys , Obesity/prevention & control , United States/epidemiology , Waist Circumference , Young Adult
12.
Int J Environ Res Public Health ; 7(7): 2988-3005, 2010 07.
Article in English | MEDLINE | ID: mdl-20717554

ABSTRACT

Recent evidence suggests that endocrine disrupting chemicals (EDCs) may cause perturbations in endogenous hormonal regulation that predispose to weight gain. Using data from NHANES (1999-2002), we investigated the association between body mass index (BMI), waist circumference (WC) and selected persistent organic pollutants (POPs) via multiple linear regressions. Consistent interaction was found between gender, ln oxychlordane and ln p,p' DDT. Also, we found an association between WC and ln oxychlordane and ln hpcdd in subjects with detectable levels of POPs, whereas an association between WC and ln p,p' DDT was observed in all subjects. Furthermore, ln Ocdd showed an increase with higher WC and BMI, whereas, ln trans-nonachlor decreased with higher BMI. Hence, BMI and WC are associated with POPs levels, making the chemicals plausible contributors to the obesity epidemic.


Subject(s)
Body Mass Index , Dioxins/adverse effects , Endocrine Disruptors/adverse effects , Hydrocarbons, Chlorinated/adverse effects , Obesity/etiology , Adolescent , Adult , Child , Cross-Sectional Studies , Female , Humans , Male , Nutrition Surveys , Public Health , Regression Analysis , United States , Waist-Hip Ratio , Young Adult
13.
Aggress Violent Behav ; 15(1): 76-82, 2010.
Article in English | MEDLINE | ID: mdl-20161505

ABSTRACT

This review examines what have been, to this point, generally two divergent lines of research: (a) effects of parental drug abuse on children, and (b) effects of children's exposure to interparental violence. A small, but growing body of literature has documented the robust relationship between drug use and intimate partner violence. Despite awareness of the interrelationship, little attention has been paid to the combined effect of these deleterious parent behaviors on children in these homes. Thus, we argue for the need to examine the developmental impact of these behaviors (both individually and combined) on children in these homes and for treatment development to reflect how each of these parent behaviors may affect children of substance abusers.

15.
PLoS One ; 4(8): e6624, 2009 Aug 13.
Article in English | MEDLINE | ID: mdl-19675667

ABSTRACT

BACKGROUND: Dropouts and missing data are nearly-ubiquitous in obesity randomized controlled trails, threatening validity and generalizability of conclusions. Herein, we meta-analytically evaluate the extent of missing data, the frequency with which various analytic methods are employed to accommodate dropouts, and the performance of multiple statistical methods. METHODOLOGY/PRINCIPAL FINDINGS: We searched PubMed and Cochrane databases (2000-2006) for articles published in English and manually searched bibliographic references. Articles of pharmaceutical randomized controlled trials with weight loss or weight gain prevention as major endpoints were included. Two authors independently reviewed each publication for inclusion. 121 articles met the inclusion criteria. Two authors independently extracted treatment, sample size, drop-out rates, study duration, and statistical method used to handle missing data from all articles and resolved disagreements by consensus. In the meta-analysis, drop-out rates were substantial with the survival (non-dropout) rates being approximated by an exponential decay curve (e(-lambdat)) where lambda was estimated to be .0088 (95% bootstrap confidence interval: .0076 to .0100) and t represents time in weeks. The estimated drop-out rate at 1 year was 37%. Most studies used last observation carried forward as the primary analytic method to handle missing data. We also obtained 12 raw obesity randomized controlled trial datasets for empirical analyses. Analyses of raw randomized controlled trial data suggested that both mixed models and multiple imputation performed well, but that multiple imputation may be more robust when missing data are extensive. CONCLUSION/SIGNIFICANCE: Our analysis offers an equation for predictions of dropout rates useful for future study planning. Our raw data analyses suggests that multiple imputation is better than other methods for handling missing data in obesity randomized controlled trials, followed closely by mixed models. We suggest these methods supplant last observation carried forward as the primary method of analysis.


Subject(s)
Obesity/therapy , Randomized Controlled Trials as Topic , Weight Loss , Data Interpretation, Statistical , Humans
16.
Hum Hered ; 68(1): 65-72, 2009.
Article in English | MEDLINE | ID: mdl-19339787

ABSTRACT

OBJECTIVES: Structured association tests (SAT), like any statistical model, assumes that all variables are measured without error. Measurement error can bias parameter estimates and confound residual variance in linear models. It has been shown that admixture estimates can be contaminated with measurement error causing SAT models to suffer from the same afflictions. Multiple imputation (MI) is presented as a viable tool for correcting measurement error problems in SAT linear models with emphasis on correcting measurement error contaminated admixture estimates. METHODS: Several MI methods are presented and compared, via simulation, in terms of controlling Type I error rates for both non-additive and additive genotype coding. RESULTS: Results indicate that MI using the Rubin or Cole method can be used to correct for measurement error in admixture estimates in SAT linear models. CONCLUSION: Although MI can be used to correct for admixture measurement error in SAT linear models, the data should be of reasonable quality, in terms of marker informativeness, because the method uses the existing data to borrow information in which to make the measurement error corrections. If the data are of poor quality there is little information to borrow to make measurement error corrections.


Subject(s)
Models, Genetic , Models, Statistical , Genetics, Population , Humans
17.
PLoS Genet ; 5(3): e1000424, 2009 Mar.
Article in English | MEDLINE | ID: mdl-19300490

ABSTRACT

Cytotoxic T-lymphocyte associated protein 4 (CTLA4) is a negative regulator of T-cell proliferation. Polymorphisms in CTLA4 have been inconsistently associated with susceptibility to rheumatoid arthritis (RA) in populations of European ancestry but have not been examined in African Americans. The prevalence of RA in most populations of European and Asian ancestry is approximately 1.0%; RA is purportedly less common in black Africans, with little known about its prevalence in African Americans. We sought to determine if CTLA4 polymorphisms are associated with RA in African Americans. We performed a 2-stage analysis of 12 haplotype tagging single nucleotide polymorphisms (SNPs) across CTLA4 in a total of 505 African American RA patients and 712 African American controls using Illumina and TaqMan platforms. The minor allele (G) of the rs231778 SNP was 0.054 in RA patients, compared to 0.209 in controls (4.462 x 10(-26), Fisher's exact). The presence of the G allele was associated with a substantially reduced odds ratio (OR) of having RA (AG+GG genotypes vs. AA genotype, OR 0.19, 95% CI: 0.13-0.26, p = 2.4 x 10(-28), Fisher's exact), suggesting a protective effect. This SNP is polymorphic in the African population (minor allele frequency [MAF] 0.09 in the Yoruba population), but is very rare in other groups (MAF = 0.002 in 530 Caucasians genotyped for this study). Markers associated with RA in populations of European ancestry (rs3087243 [+60C/T] and rs231775 [+49A/G]) were not replicated in African Americans. We found no confounding of association for rs231778 after stratifying for the HLA-DRB1 shared epitope, presence of anti-cyclic citrullinated peptide antibody, or degree of admixture from the European population. An African ancestry-specific genetic variant of CTLA4 appears to be associated with protection from RA in African Americans. This finding may explain, in part, the relatively low prevalence of RA in black African populations.


Subject(s)
Alleles , Antigens, CD/genetics , Arthritis, Rheumatoid/genetics , Black or African American/genetics , Adult , Black People/genetics , CTLA-4 Antigen , Case-Control Studies , Female , Haplotypes , Humans , Male , Middle Aged , Polymorphism, Single Nucleotide , Prevalence
18.
Hum Hered ; 66(2): 67-86, 2008.
Article in English | MEDLINE | ID: mdl-18382087

ABSTRACT

When two or more populations have been separated by geographic or cultural boundaries for many generations, drift, spontaneous mutations, differential selection pressures and other factors may lead to allele frequency differences among populations. If these 'parental' populations subsequently come together and begin inter-mating, disequilibrium among linked markers may span a greater genetic distance than it typically does among populations under panmixia [see glossary]. This extended disequilibrium can make association studies highly effective and more economical than disequilibrium mapping in panmictic populations since less marker loci are needed to detect regions of the genome that harbor phenotype-influencing loci. However, under some circumstances, this process of intermating (as well as other processes) can produce disequilibrium between pairs of unlinked loci and thus create the possibility of confounding or spurious associations due to this population stratification. Accordingly, researchers are advised to employ valid statistical tests for linkage disequilibrium mapping allowing conduct of genetic association studies that control for such confounding. Many recent papers have addressed this need. We provide a comprehensive review of advances made in recent years in correcting for population stratification and then evaluate and synthesize these methods based on statistical principles such as (1) randomization, (2) conditioning on sufficient statistics, and (3) identifying whether the method is based on testing the genotype-phenotype covariance (conditional upon familial information) and/or testing departures of the marginal distribution from the expected genotypic frequencies.


Subject(s)
Genetic Techniques , Models, Genetic , Models, Statistical , Animals , Chromosome Mapping , Female , Humans , Linkage Disequilibrium , Male
19.
Nucleic Acids Res ; 36(4): e26, 2008 Mar.
Article in English | MEDLINE | ID: mdl-18263617

ABSTRACT

Linkage studies of complex traits frequently yield multiple linkage regions covering hundreds of genes. Testing each candidate gene from every region is prohibitively expensive and computational methods that simplify this process would benefit genetic research. We present a new method based on commonality of functional annotation (CFA) that aids dissection of complex traits for which multiple causal genes act in a single pathway or process. CFA works by testing individual Gene Ontology (GO) terms for enrichment among candidate gene pools, performs multiple hypothesis testing adjustment using an estimate of independent tests based on correlation of GO terms, and then scores and ranks genes annotated with significantly-enriched terms based on the number of quantitative trait loci regions in which genes bearing those annotations appear. We evaluate CFA using simulated linkage data and show that CFA has good power despite being conservative. We apply CFA to published linkage studies investigating age-of-onset of Alzheimer's disease and body mass index and obtain previously known and new candidate genes. CFA provides a new tool for studies in which causal genes are expected to participate in a common pathway or process and can easily be extended to utilize annotation schemes in addition to the GO.


Subject(s)
Genetic Linkage , Genetic Predisposition to Disease , Genomics/methods , Quantitative Trait Loci , Vocabulary, Controlled , Alzheimer Disease , Body Mass Index , Computational Biology/methods , Genome, Human , Humans , Principal Component Analysis
20.
Arthritis Rheum ; 58(2): 349-58, 2008 Feb.
Article in English | MEDLINE | ID: mdl-18240241

ABSTRACT

OBJECTIVE: To determine whether shared epitope (SE)-containing HLA-DRB1 alleles are associated with rheumatoid arthritis (RA) in African Americans and whether their presence is associated with higher degrees of global (genome-wide) genetic admixture from the European population. METHODS: In this multicenter cohort study, African Americans with early RA and matched control subjects were analyzed. In addition to measurement of serum anti-cyclic citrullinated peptide (anti-CCP) antibodies and HLA-DRB1 genotyping, a panel of >1,200 ancestry-informative markers was analyzed in patients with RA and control subjects, to estimate the proportion of European ancestry. RESULTS: The frequency of SE-containing HLA-DRB1 alleles was 25.2% in African American patients with RA versus 13.6% in control subjects (P = 0.00005). Of 321 patients with RA, 42.1% had at least 1 SE-containing allele, compared with 25.3% of 166 control subjects (P = 0.0004). The mean estimated percent European ancestry was associated with SE-containing HLA-DRB1 alleles in African Americans, regardless of disease status (RA or control). As reported in RA patients of European ancestry, there was a significant association of the SE with the presence of the anti-CCP antibody: 86 (48.9%) of 176 patients with anti-CCP antibody-positive RA had at least 1 SE allele, compared with 36 (32.7%) of 110 patients with anti-CCP antibody-negative RA (P = 0.01, by chi-square test). CONCLUSION: HLA-DRB1 alleles containing the SE are strongly associated with susceptibility to RA in African Americans. The absolute contribution is less than that reported in RA among populations of European ancestry, in which approximately 50-70% of patients have at least 1 SE allele. As in Europeans with RA, the SE association was strongest in the subset of African American patients with anti-CCP antibodies. The finding of a higher degree of European ancestry among African Americans with SE alleles suggests that a genetic risk factor for RA was introduced into the African American population through admixture, thus making these individuals more susceptible to subsequent environmental or unknown factors that trigger the disease.


Subject(s)
Arthritis, Rheumatoid/ethnology , Arthritis, Rheumatoid/genetics , Black or African American/genetics , HLA-DR Antigens/genetics , White People/genetics , Adult , Black or African American/statistics & numerical data , Alleles , Arthritis, Rheumatoid/immunology , Epitopes/genetics , Epitopes/immunology , Female , Genetic Predisposition to Disease/ethnology , Genotype , HLA-DRB1 Chains , Humans , Male , Middle Aged , Peptides, Cyclic/genetics , Peptides, Cyclic/immunology , Seroepidemiologic Studies , White People/statistics & numerical data
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