Gene by BMI Interactions Influencing C-Reactive Protein Levels in European-Americans

C-Reactive Protein (CRP) is a biomarker indicating tissue damage, inflammation, and infection. High-sensitivity CRP (hsCRP) is an emerging biomarker often used to estimate an individual’s risk for future coronary heart disease (CHD). hsCRP levels falling below 1.00 mg/l indicate a low risk for developing CHD, levels ranging between 1.00 mg/l and 3.00 mg/l indicate an elevated risk, and levels exceeding 3.00 mg/l indicate high risk. Multiple Genome-Wide Association Studies (GWAS) have identified a number of genetic polymorphisms which influence CRP levels. SNPs implicated in such studies have been found in or near genes of interest including: CRP, APOE, APOC, IL-6, HNF1A, LEPR, and GCKR. A strong positive correlation has also been found to exist between CRP levels and BMI, a known risk factor for CHD and a state of chronic inflammation. We conducted a series of analyses designed to identify loci which interact with BMI to influence CRP levels in a subsample of European-Americans in the ARIC cohort. In a stratified GWA analysis, 15 genetic regions were identified as having significantly (p-value < 2.00*10-3) distinct effects on hsCRP levels between the two obesity strata: lean (18.50 kg/m2 < BMI < 24.99 kg/m2) and obese (BMI ≥ 30.00 kg/m2). A GWA analysis performed on all individuals combined (i.e. not a priori stratified for obesity status) with the inclusion of an additional parameter for BMI by gene interaction, identified 11 regions which interact with BMI to influence hsCRP levels. Two regions containing the genes GJA5 and GJA8 (on chromosome 1) and FBXO11 (on chromosome 2) were identified in both methods of analysis suggesting that these genes possibly interact with BMI to influence hsCRP levels. We speculate that atrial fibrillation (AF), age-related cataracts and the TGF-β pathway may be the biological processes influenced by the interaction of GJA5, GJA8 and FBXO11, respectively, with BMI to cause changes in hsCRP levels. Future studies should focus on the influence of gene x bmi interaction on AF, age-related cataracts and TGF-β.

Development of a Bayesian Joint Logistic Model to Better Study the Association between Haplotypes and Disease

In 2011, there will be an estimated 1,596,670 new cancer cases and 571,950 cancer-related deaths in the US. With the ever-increasing applications of cancer genetics in epidemiology, there is great potential to identify genetic risk factors that would help identify individuals with increased genetic susceptibility to cancer, which could be used to develop interventions or targeted therapies that could hopefully reduce cancer risk and mortality. In this dissertation, I propose to develop a new statistical method to evaluate the role of haplotypes in cancer susceptibility and development. This model will be flexible enough to handle not only haplotypes of any size, but also a variety of covariates. I will then apply this method to three cancer-related data sets (Hodgkin Disease, Glioma, and Lung Cancer). I hypothesize that there is substantial improvement in the estimation of association between haplotypes and disease, with the use of a Bayesian mathematical method to infer haplotypes that uses prior information from known genetics sources. Analysis based on haplotypes using information from publically available genetic sources generally show increased odds ratios and smaller p-values in both the Hodgkin, Glioma, and Lung data sets. For instance, the Bayesian Joint Logistic Model (BJLM) inferred haplotype TC had a substantially higher estimated effect size (OR=12.16, 95% CI = 2.47-90.1 vs. 9.24, 95% CI = 1.81-47.2) and more significant p-value (0.00044 vs. 0.008) for Hodgkin Disease compared to a traditional logistic regression approach. Also, the effect sizes of haplotypes modeled with recessive genetic effects were higher (and had more significant p-values) when analyzed with the BJLM. Full genetic models with haplotype information developed with the BJLM resulted in significantly higher discriminatory power and a significantly higher Net Reclassification Index compared to those developed with haplo.stats for lung cancer. Future analysis for this work could be to incorporate the 1000 Genomes project, which offers a larger selection of SNPs can be incorporated into the information from known genetic sources as well. Other future analysis include testing non-binary outcomes, like the levels of biomarkers that are present in lung cancer (NNK), and extending this analysis to full GWAS studies.

Outcomes assessment of a pediatric practice guideline

Objective. This study examines the structure, processes, and data necessary to assess the outcome variables, length of stay and total cost, for a pediatric practice guideline. The guideline was developed by a group of physicians and ancillary staff members representing the services that most commonly provide treatment for asthma patients at Texas Children's Hospital, as a means of standardizing care. Outcomes have needed to be assessed to determine the practice guideline's effectiveness.^ Data sources and study design. Data for the study were collected retrospectively from multiple hospital data bases and from inpatient chart reviews. All patients in this quasi-experimental study had a diagnosis of Asthma (ICD-9-CM Code 493.91) at the time of admission.^ The study examined data for 100 patients admitted between September 15, 1995 and November 15, 1995, whose physician had elected to apply the asthma practice guideline at the time of the patient's admission. The study examined data for 66 inpatients admitted between September 15, 1995 and November 15, 1995, whose physician elected not to apply the asthma practice guideline. The principal outcome variables were identified as "Length of Stay" and "Cost".^ Principal findings. The mean length of stay for the group in which the practice guideline was applied was 2.3 days, and 3.1 days for the comparison group, who did not receive care directed by the practice guideline. The difference was statistically significant (p value = 0.008). There was not a demonstrable difference in risk factors, health status, or quality of care between the groups. Although not showing statistical significance in the univariate analysis, private insurance showed a significant difference in the logistic regression model presenting an elevated odds ratio (odds ratio = 2.2 for a hospital stay $\le$2 days to an odds ratio = 4.7 for a hospital stay $\le$3 days) showing that patients with private insurance experienced greater risk of a shorter hospital stay than the patients with public insurance in each of the logistic regression models. Public insurance included; Medicaid, Medicare, and charity cases. Private insurance included; private insurance policies whether group, individual, or managed care. The cost of an admission was significantly less for the group in which the practice guideline was applied, with a mean difference between the two groups of $1307 per patient.^ Conclusion. The implementation and utilization of a pediatric practice guideline for asthma inpatients at Texas Children's Hospital has a significant impact in terms of reducing the total cost of the hospital stay and length of the hospital stay for asthma patients admitted to Texas Children's Hospital. ^

Effect of continuous gastric enteral feeding on tonometric measurement of gastric intramucosal carbon dioxide levels in healthy volunteers

Purpose. The aim of this research was to evaluate the effect of enteral feeding on tonometric measurement of gastric regional carbon dioxide levels (PrCO2) in normal healthy volunteers. Design and methods. The sample included 12 healthy volunteers recruited by the University Clinical Research Center (UCRC). An air tonometry system monitored PrCO2 levels using a tonometer placed in the lumen of the stomach via orogastric intubation. PrCO2 was automatically measured and recorded every 10 minutes throughout the five hour study period. An oral dose of famotidine 40 mg was self-administered the evening prior to and the morning of the study. Instillation of Isocal® High Nitrogen (HN) was used for enteral feeding in hourly escalating doses of 0, 40, 60, and 80 ml/hr with no feeding during the fifth hour. Results . PrCO2 measurements at time 0 and 10 minutes (41.4 ± 6.5 and 41.8 ± 5.7, respectively) demonstrated biologic precision (Levene's Test statistic = 0.085, p-value 0.774). Biologic precision was lost between T130 and T140 40 when compared to baseline TO (Levene's Test statistic = 1.70, p-value 0.205; and 3.205, p-value 0.042, respectively) and returned to non-significant levels between T270 and T280 (Levene's Test statistic = 3.083, p-value 0.043; and 2.307, p-value 0.143, respectively). Isocal® HN significantly affected the biologic accuracy of PrCO2 measurements (repeated measures ANOVA F 4.91, p-value <0.001). After 20 minutes of enteral feeding at 40 ml/hr, PrCO2 significantly increased (41.4 ± 6.5 to 46.6 ± 4.25, F = 5.4, p-value 0.029). Maximum variance from baseline (41.4 ± 6.5 to 61.3 ± 15.2, F = 17.22, p-value <0.001) was noted after 30 minutes of Isocal® HN at 80 ml/hr or 210 minutes from baseline. The significant elevations in PrCO2 continued throughout the study. Sixty minutes after discontinuation of enteral feeding, PrCO2 remained significantly elevated from baseline (41.4 ± 6.5 to 51.8 ± 9.2, F = 10.15, p-value 0.004). Conclusion. Enteral feeding with Isocal® HN significantly affects the precision and accuracy of PrCO2 measurements in healthy volunteers. ^

Quality of care for uninsured type 2 diabetic patients in a financial assistance medical home model

The medically uninsured population in the United States is 16% or 42 million people and consists of a significant number of Type 2 diabetic patients which is the predominant form of diabetes with 798,000 new cases diagnosed each year. There is limited health services research on uninsured populations concerning health system measures or specific disease conditions. ^ The purpose of this investigation was to determine the impact a newly implemented health care program had on the quality of care provided to patients with Type 2 diabetes. The primary study objective was to compare the quality of care while controlling for utilization, and health status of patients in the new program to their status during the previous financial assistance program. The research design was a retrospective matched-pairs design. The study population consisted of 225 patients who received medical care during 1996 and 1997 at the University Health System in San Antonio, Texas. ^ Six quality of care measures individually failed to demonstrate a statistically significant difference when compared between the two periods. However, an index measure reflecting the number of patients who received all six of the quality of care measures demonstrated a statistically significant increase in 1997 (p-value < 0.05). In 1996, 8 patients (2.6%) received all six medical management components. In 1997, 38 patients (16.8%) received all six medical management components. Four regression models were analyzed; two out of the four models demonstrated inconsistent results based on the program membership variable. ^ It is concluded that there has been a small effect of the Carelink program demonstrated by an increase from 8 to 38 patients receiving all quality of care components for Type 2 diabetics at the UHS. It is recommended that additional research be conducted in order to evaluate the quality of care provided to Type 2 diabetic patients. ^

Unintended pregnancy: Attitudes toward contraception of women obtaining abortions

Forty-nine percent of pregnancies in the United States are unintended and significant numbers of pregnancies are unintended for women of all ages. One possible reason for the high rate is that while 85% of women at risk for an unintended pregnancy use contraception, negative attitudes about the method used make them poor contraceptors. Negative attitudes may prevent the remaining 15% of women from using any method of birth control. This study examined adult women's attitudes toward contraception and its use to see if attitudes correlate with unintended pregnancy. ^ To obtain a sample of women experiencing unintended pregnancies, women obtaining therapeutic abortions were surveyed since almost all women obtaining therapeutic abortions are experiencing an unintended pregnancy. The study used a cross-sectional survey design and included 312 women obtaining abortions at the Planned Parenthood Surgical Services Clinic in Houston in the latter half of 1999. ^ The responses revealed a lack of knowledge about the safety and effectiveness of contraception, particularly for methods other than oral contraceptives and condoms. Thirty-four percent of the participants were uncomfortable buying contraception. While 71% of the participants said their physician recommended their use of contraception, 17% were unsure and 35% did not talk to their physician about contraception on a regular basis. ^ The attitudes of women using contraception were compared with those not using contraception and many differences were seen. Women not using contraception responded with more ‘unsure’ answers and believed contraception was more difficult to use. They felt planning ahead for the use of contraception interfered with the enjoyment of sex (p-value = 0.06). They were less likely to use contraception if their partner disapproved (p-value = 0.01) and more of them believed their church disapproved of contraception (p-value = 0.02). In comparison, women using contraception had negative attitudes about the safety of the pill (p-values = 0.01–0.08) and the effectiveness of the condom (p-value = 0.04). Therefore, the negative attitudes women using contraception had about contraception may interfere with their effective use of birth control. Those not using contraception were found to hold attitudes that may contribute to their non-use of contraception. ^

Evaluation of the city of Houston HIV/STD prevention program in Houston Independent School District (HISD) high schools

This cross-sectional study was undertaken to evaluate the impact in terms of HIV/STD knowledge and sexual behavior that the City of Houston HIV/STD prevention program in HISD high schools has had on students who have participated in it by comparing them with their peers who have not, based on self reports. The study further evaluated the program cost-effectiveness for averting future HIV infections by computing Cost-Utility Ratios based on reported sexual behavior. ^ Mixed results were obtained, indicating a statistically significant difference in knowledge with the intervention group having scored higher (p-value 0.001) but not for any of the behaviors assessed. The knowledge score outcome's overall p-value after adjusting for each stratifying variable (age, grade, gender and ethnicity) was statistically significant. The Odds Ratio of intervention group participants aged 15 years or more scoring 70% or higher was 1.86 times; that of intervention group female participants was 2.29 times; and that of intervention group Black/African American participants was 2.47 times relative to their comparison group counterparts. The knowledge score results remained statistically significant in the logistic regression model, which controlled for age, grade level, gender and ethnicity. The Odds Ratio in this case was 1.74. ^ Three scenarios based on the difference in the risk of HIV infection between the intervention and comparison group were used for computation of Cost-Utility Ratios: Base, worst and best-case scenario. The best-case scenario yielded cost-effective results for male participants and cost-saving results for female participants when using ethnicity-adjusted HIV prevalence. The scenario remained cost-effective for female participants when using the unadjusted HIV prevalence. ^ The challenge to the program is to devise approaches that can enhance benefits for male participants. If it is a threshold problem implying that male participants require more intensive programs for behavioral change, then programs should first be piloted among boys before being implemented across the board. If it is a reflection of gender differences, then we might have to go back to the drawing board and engage boys in focus group discussions that will help formulate more effective programs. Gender-blind approaches currently in vogue do not seem to be working. ^

Self-injury in a residential treatment population of children and adolescents

Objectives. The aim of this study was to describe the relationship between child-abuse and self-injury among children and adolescents living in a residential treatment center in a large urban area. ^ Methods. A retrospective study was conducted through a chart review of the residents who were placed at the center from 2003-2006. A total of 35 cases (with at least one documented incident of self-injury during placement at the residential treatment center) were age/gender matched with 35 controls (without at least one documented incident of self-injury during placement at the residential treatment center). ^ Results. In this study, the case subjects were far more likely to be victims of sexual abuse than were the controls (74.3% vs. 25.7%, respectively). Self-harm was found to be 9.5 times as frequent in the group that was exposed to sexual abuse in the source population (OR = 9.500 with a 95% CI = 2.292, 84.111). The difference was statistically significant (McNemar's test, x2 = 12.190 with 1 df. The two-tailed P value equals 0.0005). ^ Conclusion. These findings suggest that school-age and early-adolescent children who have a history of sexual abuse may engage in a variety of self-harming behaviors. Clinicians should consider a history of sexual abuse when working with self-harming children. ^

Factor H variant Y402H and the prevalence of hypertension and proteinuria: The Atherosclerosis Risk in Communities study

Hypertension is a significant risk factor for cardiovascular disease, which in turn is a major cause of morbidity and mortality worldwide. While the pathogenesis of vascular injury and subsequent end organ damage is complex, there is emerging data to support a role for the complement system in endovascular diseases. The complement Factor H Y402H polymorphism has been associated with a number of vasculopathies, including age-related macular degeneration (AMD), ischemic stroke and myocardial infarction. The current study evaluated the relationship of the Y402H polymorphism with hypertension and microalbuminuria in large the bi-racial Atherosclerosis Risk in Communities (ARIC) study. The Y402H polymorphism was found to be associated with a 48% (p-value 0.042) increase in the risk of developing incident hypertension in African American participants. No significant association was found with the Y402H polymorphism and microalbuminuria. The results from this investigation reveal the first association of the Factor H Y402H polymorphism and an increased risk of incident hypertension in African Americans. ^

Mean corpuscular volume as a marker for adherence to antiretroviral therapy among HIV infected children and adolescents in Uganda

Mean corpuscular volume, which is an inexpensive and widely available measure to assess, increases in HIV infected individuals receiving zidovudine and stavudine raising the hypothesis that it could be used as a surrogate for adherence.^ The aim of this study was to examine the association between mean corpuscular volume and adherence to antiretroviral therapy among HIV infected children and adolescents aged 0–19 years in Uganda as well as the extent to which changes in mean corpuscular volume predict adherence as determined by virologic suppression.^ The investigator retrospectively reviewed and analyzed secondary data of 158 HIV infected children and adolescents aged 0–19 years who initiated antiretroviral therapy under an observational cohort at the Baylor College of Medicine Children's Foundation - Uganda. Viral suppression was used as the gold standard for monitoring adherence and defined as viral load of < 400 copies/ml at 24 and 48 weeks. ^ Patients were at least 48 weeks on therapy, age 0.2–18.4 years, 54.4% female, 82.3% on zidovudine based regimen, 92% WHO stage III at initiation of therapy, median pre therapy MCV 80.6 fl (70.3–98.3 fl), median CD4% 10.2% (0.3%–28.0%), and mean pre therapy viral load 407,712.9 ± 270,413.9 copies/ml. For both 24 and 48 weeks of antiretroviral therapy, patients with viral suppression had a greater mean percentage change in mean corpuscular volume (15.1% ± 8.4 vs. 11.1% ± 7.8 and 2.3% ± 13.2 vs. -2.7% ± 10.5 respectively). The mean percentage change in mean corpuscular volume was greater in the first 24 weeks of therapy for patients with and without viral suppression (15.1% ± 8.4 vs. 2.3% ± 13.2 and 11.1% ± 7.8 vs. -2.7% ± 10.5 respectively). In the multivariate logistic regression model, percentage change in mean corpuscular volume ≥ 20% was significantly associated with viral suppression (adjusted OR 4.0; CI 1.2–13.3; p value 0.02). The ability of percentage changes in MCV to correctly identify children and adolescents with viral suppression was higher at a cut off of ≥ 20% (90.7%; sensitivity, 31.7%) than at ≥ 9% (82.9%; sensitivity, 78.9%). Negative predictive value was lower at ≥ 20% change (25%; specificity, 84.8%) than at ≥ 9% change (33.3%; specificity, 39.4%).^ Mean corpuscular volume is a useful marker of adherence among children and adolescents with viral suppression. ^

Hypertension and cognitive decline among patients of Alzheimer's disease

Objective. The main aim of our study is to assess the effect of hypertension on the decline in cognitive impairment among Alzheimer’s patients. Methods. We analyzed the data of AD patients enrolled in Baylor ADMDC in a prospective study design. We divided AD patients into two groups based on the definition of hypertension. We described a decline in cognitive impairment as a change of 5 points in mini-mental state examination score (MMSE) from the baseline visit. Results. Independent of covariates, AD patients with hypertension did not exhibit a significant decline in cognitive impairment after adjustment of covariates, age, race and education (Hazard Ratio (HR) = 1.07, p value 0.58, 95% confidence interval 0.84-1.39) than AD patients without hypertension. In addition, AD patients with hypertension did not experience decline in cognitive impairment sooner than AD patients without hypertension. (P value 0.83). Conclusions . Hypertension is not associated with cognitive impairment over time among patients with Alzheimer’s disease enrolled in Baylor ADMDC after other potential confounders were taken into account. These findings should not be interpreted as a basis for discouraging appropriate medical treatment of hypertension in AD patients. Greater efforts should be made to improve the recognition of hypertension as a modifiable risk factor for decline in cognitive impairment in AD population. ^

Determining the feasibility and acceptability of a garden-based nutrition curriculum for preschoolers

Obesity rates around the nation have risen to epidemic proportions. Rates of childhood obesity are at very high levels with 24.4% of preschool-aged children in the U.S. currently considered as overweight or obese. The percentage of childhood obesity is much higher in the southern part of the United States as compared to the rest of the nation. Minority populations, especially African American and Hispanic, are affected more than other ethnic groups. Obesity prevention programs are needed targeting young children <6 years of age from minority populations. Currently, there are few obesity prevention programs that have been implemented and evaluated in children <6 years of age. Gardening programs have been successful in improving the health status of elementary school children by increasing fruit and vegetable intake and increasing preferences for healthier food choices. However, there is no evidence of the feasibility and acceptability of a garden-based obesity prevention program among preschoolers. This pretest study, a classroom-based gardening curriculum program with 16 lesson plans and coordinating activities for preschool age children (3-5 years old) enrolled in Head Start, provides the opportunity to address this need. The study included 103 preschoolers from two centers and 9 teachers or teachers' aides. Qualitative data on feasibility and acceptability was collected from process evaluation forms of individual lesson plans and focus groups with teachers. Teacher questionnaires assessed individual teacher characteristics and provided feedback regarding the curriculum. Quantitative measures of teachers' self-efficacy, attitudes, and knowledge pertaining to nutrition were analyzed from pre and post-test surveys. Results revealed this preschool garden-based nutrition curriculum was both feasible and acceptable. The program improved teacher's self-efficacy, knowledge, and attitudes about nutrition, with teacher's confidence in ability to teach a gardening curriculum increasing from a mean score of 2.14 to 3.00 from pre to post test (P value = 0.0046). These results indicate implementing garden-based nutrition lessons within preschools is achievable. Employing garden-based nutrition lessons in the classroom is the first step in teaching children about nutrition and gardening concepts. Constructing gardening beds for more hands-on learning is the next proposed step in the larger parent study of this program.^

Evaluation of the T-SPOT(RTM).TB test in the diagnosis of latent tuberculosis infection in HIV-infected children in Uganda

Background. About a third of the world’s population is infected with tuberculosis (TB) with sub-Saharan Africa being the worst hit. Uganda is ranked 16th among the countries with the biggest TB burden. The burden in children however has not been determined. The burden of TB has been worsened by the advent of HIV and TB is the leading cause of mortality in HIV infected individuals. Development of TB disease can be prevented if TB is diagnosed during its latent stage and treated with isoniazid. For over a century, latent TB infection (LTBI) was diagnosed using the Tuberculin Skin Test (TST). New interferon gamma release assays (IGRA) have been approved by FDA for the diagnosis of LTBI and adult studies have shown that IGRAs are superior to the TST but there have been few studies in children especially in areas of high TB and HIV endemicity. ^ Objective. The objective of this study was to examine whether the IGRAs had a role in LTBI diagnosis in HIV infected children in Uganda. ^ Methods. Three hundred and eighty one (381) children were recruited at the Baylor College of Medicine-Bristol Meyers Squibb Children’s Clinical Center of Excellence at Mulago Hospital, Kampala, Uganda between March and August 2010. All the children were subjected to a TST and T-SPOT ®.TB test which was the IGRA chosen for this study. Sputum examination and chest x-rays were also done to rule out active TB. ^ Results. There was no statistically significant difference between the tests. The agreement between the two assays was 95.9% and the kappa statistic was 0.7 (95% CI: 0.55–0.85, p-value<0.05) indicating a substantial or good agreement. The TST was associated with older age and higher weight for age z-scores but the T-SPOT®. TB was not. Both tests were associated with history of taking anti-retroviral therapy (ART). ^ Conclusion. Before promoting use of IGRAs in children living in HIV/TB endemic countries, more research needs to be done. ^

Environmental sustainability and the human element: Decision making in National Cancer Institute-designated cancer centers and Practice Greenhealth subscribing institutions

Background. Various aspects of sustainability have taken root in the hospital environment; however, decisions to pursue sustainable practices within the framework of a master plan are not fully developed in National Cancer Institute (NCI) -designated cancer centers and subscribing institutions to the Practice Greenhealth (PGH) listserv.^ Methods. This cross sectional study was designed to identify the organizational characteristics each study group pursed to implement sustainability practices, describe the barriers they encountered and reasons behind their choices for undertaking certain sustainability practices. A web-based questionnaire was pilot tested, and then sent out to 64 NCI-designated cancer centers and 1638 subscribing institutions to the PGH listserv.^ Results. Complete responses were received from 39 NCI-designated cancer centers and 58 subscribing institutions to the PGH listserv. NCI-designated cancer centers reported greater progress in integrating sustainability criteria into design and construction projects than hospitals of institutions subscribing to the PHG listserv (p-value = <0.05). Statistically significant differences were also identified between these two study groups in undertaking work life options, conducting energy usage assessments, developing energy conservation and optimization plans, implementing solid waste and hazardous waste minimization programs, using energy efficient vehicles and reporting sustainability progress to external stakeholders. NCI-designated cancer centers were further along in implementing these programs (p-value = <0.05). In comparing the self-identified NCI-designated cancer centers to centers that indicated they were both and NCI and PGH, the later had made greater progress in using their collective buying power to pursue sustainable purchasing practices within the medical community (p-value = <0.05). In both study groups, recycling programs were well developed.^ Conclusions. Employee involvement was viewed as the most important reason for both study groups to pursue recycling initiatives and incorporated environmental criteria into purchasing decisions. A written sustainability commitment did not readily translate into a high percentage that had developed a sustainability master plan. Coordination of sustainability programs through a designated sustainability professional was not being undertaken by a large number of institutions within each study group. This may be due to the current economic downturn or management's attention to the emerging health care legislation being debated in congress. ^ Lifecycle assessments, an element of a carbon footprint, are seen as emerging areas of opportunity for health care institutions that can be used to evaluate the total lifecycle costs of products and services.^

Comparison of multiple comparison methods for identifying differential gene expression in simulated and real papillary thyroid cancer microarray data

The difficulty of detecting differential gene expression in microarray data has existed for many years. Several correction procedures try to avoid the family-wise error rate in multiple comparison process, including the Bonferroni and Sidak single-step p-value adjustments, Holm's step-down correction method, and Benjamini and Hochberg's false discovery rate (FDR) correction procedure. Each multiple comparison technique has its advantages and weaknesses. We studied each multiple comparison method through numerical studies (simulations) and applied the methods to the real exploratory DNA microarray data, which detect of molecular signatures in papillary thyroid cancer (PTC) patients. According to our results of simulation studies, Benjamini and Hochberg step-up FDR controlling procedure is the best process among these multiple comparison methods and we discovered 1277 potential biomarkers among 54675 probe sets after applying the Benjamini and Hochberg's method to PTC microarray data.^