Does Logarithm Transformation of Microarray Data Affect Ranking Order of Differentially Expressed Genes?

A common practice in microarray analysis is to transform the microarray raw data (light intensity) by a logarithmic transformation, and the justification for this transformation is to make the distribution more symmetric and Gaussian-like. Since this transformation is not universally practiced in all microarray analysis, we examined whether the discrepancy of this treatment of raw data affect the "high level" analysis result. In particular, whether the differentially expressed genes as obtained by $t$-test, regularized t-test, or logistic regression have altered rank orders due to presence or absence of the transformation. We show that as much as 20%--40% of significant genes are "discordant" (significant only in one form of the data and not in both), depending on the test being used and the threshold value for claiming significance. The t-test is more likely to be affected by logarithmic transformation than logistic regression, and regularized $t$-test more affected than t-test. On the other hand, the very top ranking genes (e.g. up to top 20--50 genes, depending on the test) are not affected by the logarithmic transformation.Comment: submitted to IEEE/EMBS Conference'0

Linkage analysis of longitudinal data

BACKGROUND: We propose a statistical model for linkage analysis of the longitudinal data. The proposed model is a mixed model based on the new Haseman and Elston model and allows several random effects. Specifically, the proposed model includes a random effect for correlation among sib pairs having one sibling in common, and one for the correlation among siblings from the same parents. RESULTS: The proposed model was applied to the analysis of the Genetic Analysis Workshop 13 simulated data set for a quantitative trait of the systolic blood pressure. A simple independence model and two kinds of random effects models yielded good power for detecting linkage for these data sets, while the random effects models performed slightly better than the independence model. Both random effects models showed similar performance. CONCLUSIONS: The proposed models seem not only quite useful in detecting linkage with the longitudinal data for the trait but also quite flexible. They can handle a wide class of correlation structures. Models with a more general class of covariance structure are desirable

A comparison of founder-only and all-pedigree-members genotype-expression association by regression analysis

Genotype-expression association analysis using linear regression may produce different test results depending on whether founders only or all pedigreed members are used. This difference is not due to the correlation of samples within a pedigree, because linear mixed models have been applied to account for that correlation. We investigated the possibility that the difference is due to a dependence of expression levels on, among other things, the generation number in the pedigree. Indeed, of the 30 or so studied expression quantitative traits, several of them show significant dependence on the generation number. We propose to use all pedigree members in genotype-expression association analyses whenever the complete genotyping information is available

Thyroid function in obese Korean children and adolescents: Korea National Health and Nutrition Examination Survey 2013–2015

Purpose In recent years, there has been an increasing focus on thyroid function in pediatric obese patients, but no nationwide study evaluating the relationship between thyroid function and obesity has yet been conducted in Korea. We aimed to evaluate thyroid dysfunction in obese Korean children. Methods We analyzed the associations between obesity and thyroid hormone levels among 975 Korean boys and girls aged 10–18 years and who participated in the Korean National Health and Nutrition Examination Survey VI (2013–2015). Results Average serum thyrotropin (TSH) and serum free thyroxine (fT4) levels in the nonobese group were 2.7±0.1 μIU/mL and 1.3±0.0 ng/dL, respectively, and those in the overweight group were 3.1±0.2 μIU/mL and 1.2±0.0 ng/dL. Serum TSH level was significantly higher in the abdominal obesity group than in the normal group (P=0.023). fT4 level was significantly lower in both the overweight and abdominal obesity groups than in the normal group (P<0.001, P=0.014). Serum TSH level was associated positively with abdominal obesity and levels of high-density lipoprotein cholesterol and triglyceride. Serum fT4 level was negatively correlated with abdominal obesity (P=0.014). Conclusions Korean children with abdominal obesity showed increased TSH and decreased fT4 levels compared to normal children

Segregation analysis of mandibular prognathism in Korean orthognathic surgery patients and their families

Objective: To investigate the existence of genetic influences on the incidence of mandibular prognathism (MP) in Korean Class Ill patients. Materials and Methods: The probands consisted of 100 Class Ill patients with MP (51 men and 49 women; mean age, 22.1 +/- 5.2 years; SNA, 81.2 degrees +/- 3.2 degrees; SNB, 84.1 degrees +/- 3.9 degrees) who underwent orthognathic surgery. Using three-generation pedigree charts, questionnaires, and clinical examinations, general information and information regarding MP for a total of 3777 relatives of the probands (1911 men and 1866 women) was ascertained. Familial correlations of MP between possible pairs in the pedigree were estimated. Heritability (h(2)) of MP under various models was estimated. Segregation analysis was conducted under the assumption of the nonpolygenic multivariate logistic model and finite polygenic mixed model. One-, two-, and three-susceptibility-type models were evaluated. Results: Among 3777 relatives, 199 (97 men and 102 women) were affected with MP (5.3%). Correlation coefficients of MP incidence in full siblings and in parent-offspring were .2003 and .2036, respectively (all P < .001). The h(2) of MP was estimated as 21.5% after adjusting for sex and founder effects. Two- and three susceptibility-type models showed that the general model fit better than the other models. MP incidence did not have a major gene transmission model and was influenced by numerous minor effect genes and their additive effects. Conclusion: These results suggest that the inherited susceptibility to MP in Korean Class Ill patients might be due to the summation of minor effects from a variety of different genes and/or influence of environmental factors, rather than Mendelian transmission of major genes.OAIID:oai:osos.snu.ac.kr:snu2013-01/102/0000004298/12SEQ:12PERF_CD:SNU2013-01EVAL_ITEM_CD:102USER_ID:0000004298ADJUST_YN:YEMP_ID:A072100DEPT_CD:852CITE_RATE:1.184FILENAME:segregation-ao-2013-final.pdfDEPT_NM:치의과학과SCOPUS_YN:YCONFIRM:

A Bayesian approach for applying Haseman-Elston methods

The main goal of this paper is to couple the Haseman-Elston method with a simple yet effective Bayesian factor-screening approach. This approach selects markers by considering a set of multigenic models that include epistasis effects. The markers are ranked based on their marginal posterior probability. A significant improvement over our previously proposed Bayesian variable selection methodology is a simple Metropolis-Hasting algorithm that requires minimum tuning on the prior settings. The algorithm, however, is also flexible enough for us to easily incorporate our hypotheses and avoid computational pitfalls. We apply our approach to the microsatellite data of Collaborative Studies on Genetics of Alcoholism using the coded values for the ALDX1 variable as our response

Longitudinal assessment of urinary ALCAM, HPX, and PRDX6 in Korean patients with systemic lupus erythematosus: implications for disease activity monitoring and treatment response

IntroductionThis study aimed to demonstrate the potential of activated leukocyte cell adhesion molecule (ALCAM), hemopexin (HPX), and peroxiredoxin 6 (PRDX6) as urine biomarkers for systemic lupus erythematosus (SLE).MethodsUrine samples were collected from 138 Korean patients with SLE from the Ajou Lupus Cohort and 39 healthy controls (HC). The concentrations of urine biomarkers were analyzed using enzyme-linked immunosorbent assay kits specific for ALCAM, HPX, and PRDX6, respectively. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic utility, and Pearson’s correlation analysis was conducted to assess the relationships between the disease activity and urine biomarkers.ResultsPatients with SLE and patients with lupus nephritis (LN) showed significantly elevated ALCAM, HPX, and PRDX6 levels compared with HCs. ALCAM, HPX, and PRDX6 showed significant diagnostic values, especially for lupus nephritis (LN), with areas under the receiver operating characteristic curve for LN was 0.850 for ALCAM (95% CI, 0.778–0.921), 0.781 for HPX (95% CI, 0.695–0.867), and 0.714 for PRDX6 (95% CI, 0.617–0.812). Correlation analysis revealed that all proteins were significantly associated with anti-double stranded DNA antibody (ALCAM, r = 0.350, p &lt; 0.001; HPX, r = 0.346, p &lt; 0.001; PRDX6, r = 0.191, p = 0.026) and SLEDAI (ALCAM, r = 0.526, p &lt; 0.001; HPX, r = 0.479, p &lt; 0.001; PRDX6, r = 0.262, p = 0.002). Results from the follow-up of the three biomarker levels in these patients revealed a significant decrease, showing a positive correlation with changes in SLEDAI-2k scores (ALCAM, r = 0.502, p &lt; 0.001; HPX, r = 0.475, p &lt; 0.001; PRDX6, r = 0.245, p = 0.026), indicating their potential as indicators for tracking disease activity.DiscussionsUrinary ALCAM, HPX, and PRDX6 levels have diagnostic value and reflect disease activity in Korean patients with SLE, emphasizing their potential for non-invasive monitoring and treatment response evaluation