Association of self-reported physical activity and performance in the physical fitness assessment among Airmen

The U.S. Air Force, as with the other branches of military services, has physical fitness standards imposed on their personnel. These standards ensure a healthy and fit combat force. To meet these standards, Airmen have to maintain a certain level of physical activity in their lifestyle. Objective. This was a cross sectional (prevalence) study to evaluate the association of Airmen's self-reported physical activity and their performance in the Air Force Physical Fitness Assessment in 2007. Methods. The self-reported physical activity data were obtained from the Air Force Web Health Assessment (AF WEB HA), a web-based health questionnaire completed by the Airmen during their annual Preventive Health Assessment. The physical activity levels were categorized as having met or not having met the Centers for Disease Control and Prevention (CDC) and the American College of Sports Medicine (ACSM) physical activity recommendations. Physical Fitness scores were collected from the Air Force Fitness Management System (AFFMS), a repository of physical fitness test data. Results. There were 49,029 Airmen who answered the AF WEB HA in 2007 and also took their physical fitness test. 94.4% (n = 46,304) of Airmen met the recommended physical activity guidelines and 79.9% (n = 39,178) passed the fitness test. Total Airmen who both met the physical activity recommendations and passed the fitness test was 75.6% (n = 37,088). Airmen who did not meet the activity recommendations and also failed the fitness test totaled 635 or 1.3% of the study group. The Mantel-Haenszel Chi-Square analysis of the data on the activity levels and the physical fitness test relationship was the following χ2 = 18.52, df 1, and p = <0.0001. The Odds Ratio (OR) was 1.22 (95% CI 1.12, 1.34). Conclusion. The study determined that there was a positive association between Airmen's self-reported physical activity and their performance in the physical fitness assessment.^

Exploring the association of children's engagement in nature and outdoor activity with physical activity: A systematic review

The natural environment and green spaces are settings that may facilitate physical activity and, as a result, combat childhood obesity and benefit children's physical health. A systematic review was conducted to assess the effect of children's engagement in outdoor activity on children's physical activity levels. A total of 169 articles were initially identified, of which 11 were eligible for inclusion in the systematic review. Studies were heterogeneous: cross-sectional, RCT, cohort, and direct observation. Study participants were between the ages of 3-15 years, and physical activity was measured by accelerometers, pedometers, direct observation or surveys. A majority of the studies (9/11) found a positive association between time spent outdoors and physical activity in children and adolescents. Of these 9 studies, 5 found this association specifically between time spent outdoors in greenspace and physical activity. Despite limitations, the findings of this review support the positive association between time spent outdoors and physical activity in children and adolescents, and the notion that children and adolescents who spend more time outdoors are more physically active. This demonstrates the need to use outdoor environments as settings for children's and adolescents' physical activity.^

Environmental and behavioral risk factors for moderate or severe rotavirus diarrhea in children less than 24 months

On a global basis rotaviruses are the most important agents involved in childhood diarrhea. In developing countries they account for 6% of all diarrheas and 20% of all diarrhea related deaths of children under 5 years of age, with over 1 billion episodes and over 4 million deaths annually. Given the disease burden, there is a need for better understanding the risk factors involved in rotavirus disease, to identify areas of intervention. In order to provide this information, two areas were developed: a review of the literature, examining the causal evidence for rotavirus diarrhea and a case comparison study. The case comparison study analyzed two areas: identifying climate factors and, identifying environmental and behavioral risk factors. The literature review showed that few analytical studies have identified specific risk factors such as home environment, and a winter seasonal trend for temperate areas, but in key areas evidence is contradictory. The case comparison study for climate factors demonstrated that seasonality occurs in a tropical country like Venezuela and that a complex interplay between weather conditions contribute to the seasonal pattern. A positive association between rain fall (OR 4.1); dew point (OR 2.3) and temperature differential during the day (OR 1.4) and, an inverse association with temperature (OR 0.5) and relative humidity (OR 0.8) was found. This information is useful in understanding the seasonal pattern of rotavirus and for planning health care needs. The second analysis demonstrated that environmental variables such as crowding (OR 14.3), contact with someone with an infectious disease (OR 4.9) and animal ownership (OR 2.3) were important. Restricting the analysis to animal owners demonstrated that living In a rural settling (OR 13.8), defecating in inappropriate places (OR 7.2), crowding(4.2) and indoor animals (4.0) are of importance. Behavioral variables identified were: lack of breast feeding (OR 4.0) and visiting when someone was sick (OR 3.4). Biological and demographic variables of importance were: age, with a dose response relationship; undernurishment (OR 11.3) and household per capita monthly income less than US $ 16.30 (OR 8.5). Using a diarrhea compeer group we found that, although some of the previous variables were of importance, no major differences were found. These findings are important in identifying paths for prevention and further research. ^

Interrelationships between the structural and functional aspects of social relationships, comorbidity and health related quality of life in breast cancer survivors

It is widely acknowledged in theoretical and empirical literature that social relationships, comprising of structural measures (social networks) and functional measures (perceived social support) have an undeniable effect on health outcomes. However, the actual mechanism of this effect has yet to be clearly understood or explicated. In addition, comorbidity is found to adversely affect social relationships and health related quality of life (a valued outcome measure in cancer patients and survivors). ^ This cross sectional study uses selected baseline data (N=3088) from the Women's Healthy Eating and Living (WHEL) study. Lisrel 8.72 was used for the latent variable structural equation modeling. Due to the ordinal nature of the data, Weighted Least Squares (WLS) method of estimation using Asymptotic Distribution Free covariance matrices was chosen for this analysis. The primary exogenous predictor variables are Social Networks and Comorbidity; Perceived Social Support is the endogenous predictor variable. Three dimensions of HRQoL, physical, mental and satisfaction with current quality of life were the outcome variables. ^ This study hypothesizes and tests the mechanism and pathways between comorbidity, social relationships and HRQoL using latent variable structural equation modeling. After testing the measurement models of social networks and perceived social support, a structural model hypothesizing associations between the latent exogenous and endogenous variables was tested. The results of the study after listwise deletion (N=2131) mostly confirmed the hypothesized relationships (TLI, CFI >0.95, RMSEA = 0.05, p=0.15). Comorbidity was adversely associated with all three HRQoL outcomes. Strong ties were negatively associated with perceived social support; social network had a strong positive association with perceived social support, which served as a mediator between social networks and HRQoL. Mental health quality of life was the most adversely affected by the predictor variables. ^ This study is a preliminary look at the integration of structural and functional measures of social relationships, comorbidity and three HRQoL indicators using LVSEM. Developing stronger social networks and forming supportive relationships is beneficial for health outcomes such as HRQoL of cancer survivors. Thus, the medical community treating cancer survivors as well as the survivor's social networks need to be informed and cognizant of these possible relationships. ^

Obesity and risk of multiple myeloma: A case-control study

Introduction. Several studies have reported a positive association of body mass index (BMI) with multiple myeloma; however, the period of adulthood where BMI is most important remains unclear. In addition, it is well known that body fat is associated with both sex-steroid hormone storage and with increasing insulin levels; therefore, it was hypothesized that the association between obesity and multiple myeloma may be attributed to increased aromatization of androgen in adipose tissue. Objective. The overall objective of this case-control study was to determine whether multiple myeloma cases had higher BMI and greater adult weight gain relative to healthy controls. In addition, we tested the hypothesis that hormone replacement therapy use among women will further increase the association between BMI and risk of multiple myeloma. This study used data from a pilot case-control study at M.D. Anderson Cancer Center (MDACC), entitled Etiology of multiple myeloma, directed by Dr. Sara Strom and Dr. Sergio Giralt. Methods. The pilot study recruited a total of 122 cases of histopathologically confirmed multiple myeloma from MDACC. Controls (n=183) were selected from a database of random digit dialing controls accrued in the Department of Epidemiology at MDACC and were frequency matched to the cases on age (±5 years), gender, and race/ethnicity. Demographic and risk factor information were obtained from all participants who completed a self-administered questionnaire. Items included in the questionnaire include demographic information, height and weight at age 25, 40 and current/diagnosis, medical history, family history of cancer, smoking and alcohol use. Statistical analysis. Initial descriptive analysis included Student's t-test and Pearson's chi-squared tests. Odds ratios and 95% confidence intervals were calculated to quantify the association between the variables of interest and multiple myeloma. A multivariable model will be developed using unconditional logistic regression. Results. MM cases were 1.79 times (95% CI=0.99-3.32) more likely to have been overweight or obese (BMI > 25 kg/m2) at age 25 relative to healthy controls after controlling for age, gender, race/ethnicty, education and family history of cancer. Being overweight or obese at age 40 was not significantly associated with mutliple myeloma risk (OR=1.42, 95% CI=0.86-2.34) nor was being overweight or obses at diagnosis (OR=1.43, 95% CI=0.78, 2.63). We observed a statistically significant 2-fold increased odds of multiple myeloma in individuals who gained more than 4.7 kg during between 25 and 40 years (OR=1.97, 95% CI=1.15-3.39). When assessing HRT as a modifier of the BMI and multiple myeloma association among women (N=123), no association between obesity and MM status was observed among women who have never used HRT (OR=0.60, 95% CI=0.23-1.61; n=73). Yet among women who have ever used HRT (n=50), being overweight or obese was associated with an increase in MM risk (OR=2. 93, 95% CI=0.81-10.6) after adjusting for age; however, the association was not statistically significant. Significance. This study provides further evidence that increased BMI increases the risk of multiple myeloma. Furthermore, among women, HRT use may modify risk of disease. ^

Determining appropriate measurement methods for etiological research of computing-related musculoskeletal symptoms and disorders

Two studies among college students were conducted to evaluate appropriate measurement methods for etiological research on computing-related upper extremity musculoskeletal disorders (UEMSDs). ^ A cross-sectional study among 100 graduate students evaluated the utility of symptoms surveys (a VAS scale and 5-point Likert scale) compared with two UEMSD clinical classification systems (Gerr and Moore protocols). The two symptom measures were highly concordant (Lin's rho = 0.54; Spearman's r = 0.72); the two clinical protocols were moderately concordant (Cohen's kappa = 0.50). Sensitivity and specificity, endorsed by Youden's J statistic, did not reveal much agreement between the symptoms surveys and clinical examinations. It cannot be concluded self-report symptoms surveys can be used as surrogate for clinical examinations. ^ A pilot repeated measures study conducted among 30 undergraduate students evaluated computing exposure measurement methods. Key findings are: temporal variations in symptoms, the odds of experiencing symptoms increased with every hour of computer use (adjOR = 1.1, p < .10) and every stretch break taken (adjOR = 1.3, p < .10). When measuring posture using the Computer Use Checklist, a positive association with symptoms was observed (adjOR = 1.3, p < 0.10), while measuring posture using a modified Rapid Upper Limb Assessment produced unexpected and inconsistent associations. The findings were inconclusive in identifying an appropriate posture assessment or superior conceptualization of computer use exposure. ^ A cross-sectional study of 166 graduate students evaluated the comparability of graduate students to College Computing & Health surveys administered to undergraduate students. Fifty-five percent reported computing-related pain and functional limitations. Years of computer use in graduate school and number of years in school where weekly computer use was ≥ 10 hours were associated with pain within an hour of computing in logistic regression analyses. The findings are consistent with current literature on both undergraduate and graduate students. ^

Associations between vaccination and childhood cancers in Texas counties

Background. In Dr. Mel Greaves "delayed-infection hypothesis," postponed exposure to common infections increases the likelihood of childhood cancer. Hygienic advancements in developed countries have reduced children's exposure to pathogens and children encounter common infectious agents at an older age with an immune system unable to deal with the foreign antigens. Vaccinations may be considered to be simulated infections as they prompt an antigenic response by the immune system. Vaccinations may regulate the risk of childhood cancer by modulating the immune system. The aim of the study was to determine if children born in Texas counties with higher levels of vaccination coverage were at a reduced risk for childhood cancer.^ Methods. We conducted a case-control study to examine the risk of childhood cancers, specifically leukemia, brain tumors, and non-Hodgkin lymphoma, in relation to vaccination rates in Texas counties. We utilized a multilevel mixed-effects regression model of the individual data from the Texas Cancer Registry (TCR) with group-level exposure data (i.e., the county- and public health region-level vaccination rates).^ Results. Utilizing county-level vaccination rates and controlling for child's sex, birth year, ethnicity, birth weight, and mother's age at child's birth the hepatitis B vaccine revealed negative associations with developing all cancer types (OR = 0.81, 95% CI: 0.67–0.98) and acute lymphoblastic leukemia (ALL) (OR = 0.63, 95% CI: 0.46–0.88). The decreased risk for ALL was also evident for the inactivated polio vaccine (IPV) (OR = 0.67, 95% CI: 0.49–0.92) and 4-3-1-3-3 vaccination series (OR = 0.62, 95% CI: 0.44-0.87). Using public health region vaccine coverage levels, an inverse association between the Haemophilus influenzae type b (Hib) vaccine and ALL (OR: 0.58; 95% CI: 0.42–0.82) was present. Conversely, the measles, mumps, and rubella (MMR) vaccine resulted in a positive association with developing non-Hodgkin lymphoma (OR = 2.81, 95% CI: 1.27–6.22). ^

An examination of spirituality, self efficacy, and smoking cessation among adults in Houston, Texas

Over the past decade there has been a growing interest in the association between spirituality and health outcomes. Little is known about the role of spirituality among adult smokers who are motivated to stop smoking. The purpose of this dissertation is to examine the relations among immutable individual differences, spirituality, and self efficacy among adults motivated to stop smoking. The first paper of this dissertation systematically reviewed literature to measure the concordance between spirituality and smoking status among adults in the United States. The second paper of this dissertation explored the association between spirituality and smoking cessation. We hypothesized that higher levels of spirituality were positively associated with smoking cessation. The third paper of this dissertation examined the association between perceived self efficacy and spirituality. We hypothesized that both high levels of self efficacy and spirituality were positively associated with smoking cessation.^ A total of 152 citations were identified based on the preliminary search of databases and reference lists. After a preliminary title- and abstract-based review, 17 full text articles were retrieved for further assessment. Of these, eight met the criteria for inclusion. Results of the systematic review suggest that there is inconsistent evidence to support or refute an association between spirituality and smoking status among adults.^ Smokers (N = 200) at least 18 years of age enrolled in a minimal contact smoking cessation intervention in Houston, Texas completed questionnaires. To examine our hypotheses we conducted cross-sectional analyses of responses to questions included in selected baseline questions and the final in-person visit three weeks post-quit day. Results of the logistic regression analyses indicated that individuals with higher levels of spirituality and self efficacy were significantly more likely to abstain from smoking. The positive association is also evident when controlling for employment, income, race, education, and nicotine dependence. The interaction between self efficacy and spirituality was not statistically significant in predicting smoking abstinence.^ Recommendations for future research and implications for smoking cessation interventions are discussed. Further research in this area would benefit from using standard measures of abstinence, recruiting larger and more diverse populations, and using longitudinal study designs.^

Low birthweight and the risk of developing subsequent high blood pressure and/or dyslipidemia in childhood

The association between birthweight and blood pressure (BP), and birthweight and serum lipid concentrations at age 7 through 11 years was examined in 1446 black and white children. The prevalence ratio (with 95% confidence interval) for being in the race-, sex- and age-specific upper decile of diastolic BP in children born with low birthweight (LBW, $<$2500 grams) versus children with birthweight $\geq$2500 grams was for black boys, 2.66 (1.24-5.70). In the other race-sex groups for diastolic BP, and in all race-sex groups for systolic BP this ratio did not differ from one. Among white boys with LBW, but not in the other race-sex groups, higher than expected percentages of subjects were in the highest decile group of triglyceride concentrations (0.01 $<$ p $<$ 0.05). The prevalence ratio was 2.42 (1.19-4.91). When prematures were excluded only more than expected white girls with LBW were in the highest decile group of triglyceride concentrations. The prevalence ratio was 3.23 (1.16-9.00). Prevalence ratios for triglyceride concentrations in black boys and girls, and for LDL/HDL-C ratio, cholesterol and VLDL-C concentrations in all race-sex groups were not different from one in analyses including and in those excluding prematures. Mean triglyceride concentrations stratified by tertiles of Quetelet Index, race and sex showed a strongly positive association between triglyceride concentrations and Quetelet Index, and in the upper tertile of the Quetelet Index an association between LBW and raised triglyceride concentrations. Multiple linear regression analyses showed that after adjusting for sex, race and age present Quetelet Index (p $<$ 0.001) is a much stronger predictor of systolic and diastolic BP, and also of LDL-C/HDL-C ratio and triglyceride concentrations in this age group than birthweight (p $>$ 0.05). Thus, an association between LBW and subsequent risk for elevated BP was confirmed for diastolic BP in black boys, but not for the other race-sex groups, and not for systolic BP in any group. This is the first study finding an association between LBW and elevated triglyceride concentrations in boys (white and black) and girls (white). A follow-up study to assess whether the findings can be confirmed at adult age is recommended. ^

A feasibility study for assessing building occupants' indoor air quality expectations compared to nationally recognized standards

Indoor Air Quality (IAQ) can have significant implications for health, productivity, job performance, and operating cost. Professional experience in the field of indoor air quality suggests that high expectations (better than nationally established standards) (American Society of Heating, Refrigerating, and Air-conditioning Engineers (ASHRAE)) of workplace indoor air quality lead to increase air quality complaints. To determine whether there is a positive association between expectations and indoor air quality complaints, a one-time descriptive and analytical cross-sectional pilot study was conducted. Area Safety Liaisons (n = 330) at University of Texas Health Science Center – Houston were asked to answer a questionnaire regarding their expectations of four workplace indoor air quality indicators i.e., (temperature, relative humidity, carbon dioxide, and carbon monoxide) and if they experienced and reported indoor air quality problems. A chi-square test for independence was used to evaluate associations among the variables of interest. The response rate was 54% (n = 177). Results did not show significant associations between expectation and indoor air quality. However, a greater proportion of Area Safety Liaisons who expected indoor air quality indicators to be better than the established standard experienced greater indoor air quality problems. Similarly, a slightly higher proportion of Area Liaisons who expected indoor air quality indicators to be better than the standard reported greater indoor air quality complaints. ^ The findings indicated that a greater proportion of Area Safety Liaisons with high expectations (conditions that are beyond what is considered normal and acceptable by ASHRAE) experienced greater indoor air quality discomfort. This result suggests a positive association between high expectations and experienced and reported indoor air quality complaints. Future studies may be able to address whether the frequency of complaints and resulting investigations can be reduced through information and education about what are acceptable conditions.^

The relationship of obesity and cardiovascular disease

Aim. To review published literature on the relationship of obesity and cardiovascular disease.^ Methods. To look at all the studies published on the topic from 2005.^ Results. In the studies done prior to 2011, body mass index and in particular waist to hip ratio (51.57) was found to be associated with coronary heart disease. But, this relationship was challenged by the latest Lancet 2011meta-analysis 1 which concluded that singly or in combination, body-mass index, waist circumference, and waist-to-hip ratio did not importantly improve prediction of first-onset cardiovascular disease when additional information exists on blood pressure, history of diabetes, and cholesterol measures were available. Furthermore, they also found long-term reproducibility of BMI to be superior to that of waist-to-hip ratio (or waist circumference). Interestingly, body mass index in later childhood and early adult life showed positive association with coronary heart disease later in life 2. In US female health professionals 3 increasing body mass index was found to be associated with increased coronary heart disease risk. Overall 4, physical activity was found to be independently associated with fewer risk factors, less coronary artery disease, and fewer adverse events in women. Finally, obesity was found to be associated with increased overall cardiovascular mortality and coronary heart disease mortality 5.^ Conclusions. There is insufficient data to draw guidelines regarding parameters of obesity affecting cardiovascular disease. But there is data to support that lower body mass index would lead to decreased cardiovascular disease mortality. And physical activity has a direct association with less coronary artery disease in women.^

Objective assessment of the built environment and its relationship to physical activity and obesity

The role of physical activity in the promotion of individual and population health has been well documented in research and policy publications. Significant research activities have produced compelling evidence for the support of the positive association between physical activity and improved health. Despite the knowledge about these public health benefits of physical activity, over half of US adults do not engage in physical activity at levels consistent with public health recommendations. Just as physical inactivity is of significant public health concern in the US, the prevalence of obesity (and its attendant co-morbidities) is also increasing among US adults.^ Research suggests racial and ethnic disparities relevant to physical inactivity and obesity in the US. Various studies have shown more favorable outcomes among non-Hispanic whites when compared to other minority groups as far as physical activity and obesity are concerned. The health disparity issue is especially important because Mexican-Americans who are the fastest growing segment of the US population are disproportionately affected by physical inactivity and obesity by a significant margin (when compared to non-Hispanic whites), so addressing the physical inactivity and obesity issues in this group is of significant public health concern. ^ Although the evidence for health benefits of physical activity is substantial, various research questions remain on the potential motivators for engaging in physical activity. One area of emerging interest is the potential role that the built environment may play in facilitating or inhibiting physical activity.^ In this study, based on an ongoing research project of the Department of Epidemiology at the University of Texas M. D. Anderson Cancer Center, we examined the built environment, measured objectively through the use of geographical information systems (GIS), and its association with physical activity and obesity among a cohort of Mexican- Americans living in Harris County, Texas. The overall study hypothesis was that residing in dense and highly connected neighborhoods with mixed land-use is associated with residents’ increased participation in physical activity and lowered prevalence of obesity. We completed the following specific aims: (1) to generate a land-use profile of the study area and create a “walkability index” measure for each block group within the study area; (2) to compare the level of engagement in physical activity between study participants that reside in high walkability index block groups and those from low walkability block groups; (3) to compare the prevalence of obesity between study participants that reside in high walkability index block groups and those from low walkability block groups. ^ We successfully created the walkability index as a form of objective measure of the built environment for portions of Harris County, Texas. We used a variety of spatial and non-spatial dataset to generate the so called walkability index. We are not aware of previous scholastic work of this kind (construction of walkability index) in the Houston area. Our findings from the assessment of relationships among walkability index, physical activity and obesity suggest the following, that: (1) that attempts to convert people to being walkers through health promotion activities may be much easier in high-walkability neighborhoods, and very hard in low-walkability neighborhoods. Therefore, health promotion activities to get people to be active may require supportive environment, walkable in this case, and may not succeed otherwise; and (2) Overall, among individuals with less education, those in the high walkability index areas may be less obese (extreme) than those in the low walkability area. To the extent that this association can be substantiated, we – public health practitioners, urban designers, and policy experts – we may need to start thinking about ways to “retrofit” existing urban forms to conform to more walkable neighborhoods. Also, in this population especially, there may be the need to focus special attention on those with lower educational attainment.^

The effects of omega -3 fatty acid -enriched fish on C -reactive protein levels in postmenopausal women

Coronary heart disease (CHD) is the leading cause of death in women and rates markedly increase among women after 65 years of age. C-reactive protein (CRP) is a new clinical indicator of atherosclerotic-related inflammation with a direct pathogenic role. Studies show lifestyle factors can modulate CRP. Omega-3 fatty acids have anti-inflammatory properties and studies suggest that eating fish high in omega-3 fatty acids may lower CHD risk in women. This study sought to assess the possible role of omega-3 fatty acids in the reduction of CHD-related inflammation by investigating the effect of fish consumption on CRP levels. Methods. Twenty-four healthy postmenopausal women were randomly assigned to a fish group (usual diet plus two servings per week of enriched fish) or control group (usual diet with no fatty fish) for eight weeks. Omega-3 fatty acid-enriched fish developed by the West Virginia University Aquaculture Division was used. Serum CRP, serum interleukin-6 (IL-6), and the fatty acid content of red blood cells (RBC) were measured before and after the study. Women also completed food records. RESULTS: Baseline levels of CRP were low (85% of the fish group had normal levels) and few changes in CRP risk category were observed. Mean IL-6 levels were reduced by 27% and 35% in the fish and control groups, respectively (p for between-group difference = 0.60). Changes in RBC fatty acid composition were not statistically significant. Compared to control women, women in the fish group had greater reductions in mean triglycerides (p = 0.08), total cholesterol (P = 0.04), and LDL cholesterol levels (p = 0.06). Baseline dietary intake of total and monounsaturated fatty acids tended to be positively associated with baseline CRP, while vitamin E intake was inversely related. Saturated fat intake tended to have a positive association with IL-6. Conclusions. Findings regarding the effect of two servings of fish on CRP and IL-6 levels are inconclusive due to low baseline levels of CRP and IL-6. However, results indicate two servings of fatty fish have favorable effects on blood lipids. The relationship of dietary components with CRP and IL-6 is complex and further research is needed to determine the varying roles of diet on the inflammatory process. ^

HLA-DPB1 and DPB2 are genetic loci for systemic sclerosis: a genome-wide association study in Koreans with replication in North Americans.

OBJECTIVE: To identify systemic sclerosis (SSc) susceptibility loci via a genome-wide association study. METHODS: A genome-wide association study was performed in 137 patients with SSc and 564 controls from Korea using the Affymetrix Human SNP Array 5.0. After fine-mapping studies, the results were replicated in 1,107 SSc patients and 2,747 controls from a US Caucasian population. RESULTS: The single-nucleotide polymorphisms (SNPs) (rs3128930, rs7763822, rs7764491, rs3117230, and rs3128965) of HLA-DPB1 and DPB2 on chromosome 6 formed a distinctive peak with log P values for association with SSc susceptibility (P=8.16x10(-13)). Subtyping analysis of HLA-DPB1 showed that DPB1*1301 (P=7.61x10(-8)) and DPB1*0901 (P=2.55x10(-5)) were the subtypes most susceptible to SSc in Korean subjects. In US Caucasians, 2 pairs of SNPs, rs7763822/rs7764491 and rs3117230/rs3128965, showed strong association with SSc patients who had either circulating anti-DNA topoisomerase I (P=7.58x10(-17)/4.84x10(-16)) or anticentromere autoantibodies (P=1.12x10(-3)/3.2x10(-5)), respectively. CONCLUSION: The results of our genome-wide association study in Korean subjects indicate that the region of HLA-DPB1 and DPB2 contains the loci most susceptible to SSc in a Korean population. The confirmatory studies in US Caucasians indicate that specific SNPs of HLA-DPB1 and/or DPB2 are strongly associated with US Caucasian patients with SSc who are positive for anti-DNA topoisomerase I or anticentromere autoantibodies.

Single nucleotide polymorphism (SNP) selection for genotype-phenotype association studies

With hundreds of single nucleotide polymorphisms (SNPs) in a candidate gene and millions of SNPs across the genome, selecting an informative subset of SNPs to maximize the ability to detect genotype-phenotype association is of great interest and importance. In addition, with a large number of SNPs, analytic methods are needed that allow investigators to control the false positive rate resulting from large numbers of SNP genotype-phenotype analyses. This dissertation uses simulated data to explore methods for selecting SNPs for genotype-phenotype association studies. I examined the pattern of linkage disequilibrium (LD) across a candidate gene region and used this pattern to aid in localizing a disease-influencing mutation. The results indicate that the r2 measure of linkage disequilibrium is preferred over the common D′ measure for use in genotype-phenotype association studies. Using step-wise linear regression, the best predictor of the quantitative trait was not usually the single functional mutation. Rather it was a SNP that was in high linkage disequilibrium with the functional mutation. Next, I compared three strategies for selecting SNPs for application to phenotype association studies: based on measures of linkage disequilibrium, based on a measure of haplotype diversity, and random selection. The results demonstrate that SNPs selected based on maximum haplotype diversity are more informative and yield higher power than randomly selected SNPs or SNPs selected based on low pair-wise LD. The data also indicate that for genes with small contribution to the phenotype, it is more prudent for investigators to increase their sample size than to continuously increase the number of SNPs in order to improve statistical power. When typing large numbers of SNPs, researchers are faced with the challenge of utilizing an appropriate statistical method that controls the type I error rate while maintaining adequate power. We show that an empirical genotype based multi-locus global test that uses permutation testing to investigate the null distribution of the maximum test statistic maintains a desired overall type I error rate while not overly sacrificing statistical power. The results also show that when the penetrance model is simple the multi-locus global test does as well or better than the haplotype analysis. However, for more complex models, haplotype analyses offer advantages. The results of this dissertation will be of utility to human geneticists designing large-scale multi-locus genotype-phenotype association studies. ^