Theoretical and experimental studies of linkage disequilibrium in human populations

Linkage disequilibrium (LD) is defined as the nonrandom association of alleles at two or more loci in a population and may be a useful tool in a diverse array of applications including disease gene mapping, elucidating the demographic history of populations, and testing hypotheses of human evolution. However, the successful application of LD-based approaches to pertinent genetic questions is hampered by a lack of understanding about the forces that mediate the genome-wide distribution of LD within and between human populations. Delineating the genomic patterns of LD is a complex task that will require interdisciplinary research that transcends traditional scientific boundaries. The research presented in this dissertation is predicated upon the need for interdisciplinary studies and both theoretical and experimental projects were pursued. In the theoretical studies, I have investigated the effect of genotyping errors and SNP identification strategies on estimates of LD. The primary importance of these two chapters is that they provide important insights and guidance for the design of future empirical LD studies. Furthermore, I analyzed the allele frequency distribution of 26,530 single nucleotide polymorphisms (SNPs) in three populations and generated the first-generation natural selection map of the human genome, which will be an important resource for explaining and understanding genomic patterns of LD. Finally, in the experimental study, I describe a novel and simple, low-cost, and high-throughput SNP genotyping method. The theoretical analyses and experimental tools developed in this dissertation will facilitate a more complete understanding of patterns of LD in human populations. ^

Sociodemographic characteristics as predictors of successful smoking cessation among a group of Hispanic Spanish speaking smokers

Few studies have examined predictors of smoking abstinence among Hispanic groups. The purpose of this dissertation was to examine the relations of sociodemographic characteristics and smoking related factors with smoking abstinence among a group of Hispanic Spanish speaking smokers. This study utilized previously collected data from Hispanic Spanish-speaking smokers (N = 246) who participated in a study entitled Smoking Cessation Services for Hispanic Smokers in Texas. ^ The first study examined sociodemographic characteristics and smoking related mechanisms that predicted smoking abstinence among this group. Two of the characteristics were related to smoking abstinence, marital status and acculturation level. Being unmarried increased the likelihood of being abstinent at the 12 week assessment (OR = 1.80). Those in the high acculturation group were twice as likely to be abstinent (OR = 2.24). Of the smoking related mechanisms, those with higher positive reinforcement expectancies were less likely to be abstinent (OR = .86), as were those with a higher level of affiliative attachment (OR = .86), a higher level of craving (OR = .78) and a higher tolerance to the effect of smoking (OR = .74). The second study was to examine the relationship of objective measures of socioeconomic status (SES) (income, education, or employment) with smoking abstinence among this group. This study also compared the relationship of a subjective measure of SES (Social Status Ladder) to smoking abstinence. None of the objective measures of SES were related to smoking abstinence at the 12 week assessment. The subjective measure of SES did predict smoking abstinence (OR = 1.9) indicting that those that rated themselves ≤4 on the SES scale were more likely to be abstinent. ^ Although this group was recruited using various methods across the state of Texas, the fact that they preferred to interact with the counselor in Spanish may limit the study findings. The results of this study highlight the need for research to examine specific subgroups of people and understand the special circumstances that influence their health behaviors. Furthering our knowledge of the relations between sociodemographic characteristics and smoking cessation could lead to interventions that reduce disparities in smoking cessation. ^

Global practice experience: A useful lens for understanding patient and staff perceptions of successful integration of health information technology in primary care

Making healthcare comprehensive and more efficient remains a complex challenge. Health Information Technology (HIT) is recognized as an important component of this transformation but few studies describe HIT adoption and it's effect on the bedside experience by physicians, staff and patients. This study applied descriptive statistics and correlation analysis to data from the Patient-Centered Medical Home National Demonstration Project (NDP) of the American Academy of Family Physicians. Thirty-six clinics were followed for 26 months by clinician/staff questionnaires and patient surveys. This study characterizes those clinics as well as staff and patient perspectives on HIT usefulness, the doctor-patient relationship, electronic medical record (EMR) implementation, and computer connections in the practice throughout the study. The Global Practice Experience factor, a composite score related to key components of primary care, was then correlated to clinician and patient perspectives. This study found wide adoption of HIT among NDP practices. Patient perspectives on HIT helpfulness on the doctor-patient showed a suggestive trend that approached statistical significance (p = 0.172). Clinicians and staff noted successful integration of EMR into clinic workflow and their perception of helpfulness to the doctor-patient relationship show a suggestive increase also approaching statistical significance (p=0.06). GPE was correlated with clinician/staff assessment of a helpful doctor-patient relationship midway through the study (R 0.460, p = 0.021) with the remaining time points nearing statistical significance. GPE was also correlated to both patient perspectives of EMR helpfulness in the doctor-patient relationship (R 0.601, p = 0.001) and computer connections (R 0.618, p = 0.0001) at the start of the study. ^