WHOLE GENOME ANALYSIS OF SINGLE NUCLEOTIDE POLYMORPHISM ALLELE FREQUENCY AND FALSE POSITIVE RATE

Genome-wide association (GWA) studies are used widely for detecting gene variants' contribution to diseases and traits. Recent researches indicate to several methodological challenges in the study design for GWA, for example, sample size issues, power calculations, false positive rate adjustments, and commercial chips' coverage of the genome. Chromosomal regions can also influence the observed genetic diversity under certain conditions; mainly the regions of secondary structures and large-scale repeats may affect the fidelity in marker genotyping. This study was to find such regions that contained markers with more variability and to examine the correlation of this variability to the factors relevant in a GWA study design, such as the false positive rate. We enrolled healthy controls from eight independent GWA designs then assigned randomly into case and control status. Minor allele frequency estimates, and case-control association analyses were performed using PLINK for sets with different sample sizes. Marker numbers exhibiting high variability in the allele frequency estimates, and the average number of false positives were calculated for bins across the autosomal genome. We found that SNP variability (in allele frequency) was unrelated to the sample size. More variable regions correlated to regions of more average number of false positives, after adjusting for confounders, such as sample size. We suggested that regions with more variability might have structural characteristics that made them difficult to be scanned during the genotyping process. Our study has great public health relevance because regions with more variability could undermine the effective study of a candidate genes and disease relationship during a research, or worse leading to erroneous conclusions. We advise in studying these regions, the researchers could lower their false positive rates to avoid inaccurately significant levels

Quantitative assessment of female pattern hair loss

AbstractBackground/ObjectiveThe conventional approach to evaluate female pattern hair loss (FPHL) is to visually inspect and score images of balding area (BA). However, visual estimates vary widely among different physicians, and may hinder objective assessment of hair loss and subsequent treatment response. For this reason, we propose a quantitative method using a computer-aided imaging system to help physicians evaluate the severity of FPHL clinically.MethodsWe use a series of digital image processing techniques to measure the width of central balding area of FPHL. A total of 184 photos were collected form 33 Chinese women with FPHL (stages I-2 to II-2 on the Savin scale). Each photograph underwent standardized exposure correction. The balding areas were detected through this computer system and then transformed into an equivalent ellipse by principal component analysis. The width of ellipse [balding width (BW)] was measured. Spearman's rank correlation was used to detect the correlation between our measurements and clinical staging.ResultsExposure correction resulted in a 16.97% (|BWcorrected − BWoriginal|/BWcorrected) difference in BW.‏ The average BW was 54.98 mm in all patients, 25.79 mm in type I-2 patients, 37.41 mm in I-3, 54.08 mm in I-4, 72.10 mm in II-1, and 85.53 mm in II-2. The values of BW were correlated with Savin scale stages clinically (rBW = 0.967), which was significant statistically (p < 0.05).ConclusionA computer-aided imaging system could be a useful tool to assist physicians to evaluate the balding area more precisely for clinical staging in FPHL. The BW instead of the balding area is simple to use clinically to represent the severity of FPHL

Prognostic factors associated with the survival of oral and pharyngeal carcinoma in Taiwan

<p>Abstract</p> <p>Background</p> <p>In Taiwan, a distinct ethnic group variation in incidence and mortality rates has been suggested for most carcinomas. Our aim is to identify the role of prognostic factors associated with the survival of oral and pharyngeal carcinoma in Taiwan.</p> <p>Methods</p> <p>Taiwan Cancer Registry records of 9039 subjects diagnosed with oral and pharyngeal carcinoma were analyzed. The population was divided into three ethnic groups by residence, which were Taiwanese aborigines, Hakka and Hokkien communities. Five-year survival rates were estimated by Kaplan-Meier methods. Ethnic curves differed significantly by log-rank test; therefore separate models for Taiwanese aborigines, Hakka and Hokkien were carried out. The Cox multivariate proportional hazards model was used to examine the role of prognostic factors on ethnic survival.</p> <p>Results</p> <p>The five-year survival rates of oral and pharyngeal carcinoma were significantly poorer for Hokkien community (53.9%) and Taiwanese aborigines community (58.1%) compared with Hakka community (60.5%). The adjusted hazard ratio of Taiwanese aborigines versus Hakka was 1.07 (95%CI, 0.86–1.33) for oral and pharyngeal carcinoma mortality, and 1.16 (95%CI, 1.01–1.33) for Hokkien versus Hakka. Males had significantly poor prognosis than females. Subjects with tongue and/or mouth carcinoma presented the worst prognosis, whereas lip carcinoma had the best prognosis. Subjects with verrucous carcinoma had better survival than squamous cell carcinoma. Prognosis was the worst in elderly subjects, and subjects who underwent surgery had the highest survival rate.</p> <p>Conclusion</p> <p>Our study presented that predictive variables in oral and pharyngeal carcinoma survival have been: ethnic groups, period of diagnosis, gender, diagnostic age, anatomic site, morphologic type, and therapy.</p

The potential impact of primary headache disorders on stroke risk

Distribution of PHDs. (DOC 55 kb

Relationships between serum HER2 ECD, TIMP-1 and clinical outcomes in Taiwanese breast cancer

<p>Abstract</p> <p>Background</p> <p>Serum levels of the extracellular domain of HER2/neu (HER2 ECD) have been demonstrated to be associated with clinical outcomes. A disintegrin and metalloproteinase-10, a sheddase of HER2/neu, can drive cancer progression and its activity is inhibited by tissue inhibitor of metalloproteinase-1 (TIMP-1). However, elevated TIMP-1 expression has been associated with a poor prognosis of breast cancer. Therefore, this study was performed to explore the relationships between serum HER2 ECD, TIMP-1 and clinical outcomes.</p> <p>Methods</p> <p>One hundred and eighty-five female breast cancer patients, who received curative mastectomy without neo-adjuvant chemotherapy at Chang-Gung Memorial Hospital, were recruited with informed consent for this study. Pre-operative serum levels of HER2 ECD and TIMP-1 were measured using an enzyme-linked immunosorbent assay.</p> <p>Results</p> <p>Twenty-three cases (12.4%) were classified HER2 ECD positive. HER2 ECD positivity was significantly associated with age, lymph node involvement, histological grade, estrogen receptor status, progesterone receptor status, tissue HER2/neu overexpression, and disease-free survival (DFS). In an age, stage, ER and HER2/neu status matched subgroup (N = 41), the serum level of TIMP-1 was significantly associated with HER2 ECD positivity and DFS.</p> <p>Conclusions</p> <p>A high serum TIMP-1 was significantly associated with HER2 ECD positivity and a poorer DFS among Taiwanese primary breast cancer patients with HER2 overexpression.</p

Integrated multiomics approach identifies calcium and integrin-binding protein-2 as a novel gene for pulse wave velocity

Background: Carotid-femoral pulse wave velocity (PWV) is an important measure of arterial stiffness, which is an independent predictor of cardiovascular morbidity and mortality. In this study, we used an integrated genetic, epigenetic and transcriptomics approach to uncover novel molecular mechanisms contributing to PWV. Methods and results: We measured PWV in 1505 healthy twins of European descendent. A genomewide association analysis was performed using standardized residual of the inverse of PWV. We identified one single-nucleotide polymorphism (rs7164338) in the calcium and integrin-binding protein-2 (CIB2) gene on chromosome 15q25.1 associated with PWV [beta = -0.359, standard error (SE) = 0.07, P = 4.8 x 10(-8)]. The same variant was also associated with increased CIB2 expression in leucocytes (beta = 0.034, SE = 0.008, P = 4.95 x 10(-5)) and skin (beta = 0.072, SE = 0.01, P = 2.35 x 10(-9)) and with hypomethylation of the gene promoter (beta = -.899, SE = 0.098, P = 3.63 x 10(-20)). Conclusion: Our data indicate that reduced methylation of the CIB2 promoter in individuals carrying rs7164338 may lead to increased CIB2 expression. Given that CIB2 is thought to regulate intracellular calcium levels, an increase in protein levels may prevent the accumulation of serum calcium and phosphate, ultimately slowing down the process of vascular calcification. This study shows the power of integrating multiple omics to discover novel cardiovascular mechanisms

Fever Screening at Airports and Imported Dengue

Airport fever screening in Taiwan, July 2003–June 2004, identified 40 confirmed dengue cases. Results obtained by capture immunoglobulin (Ig) M and IgG enzyme-linked immunoassay, real time 1-step polymerase chain reaction, and virus isolation showed that 33 (82.5%) of 40 patients were viremic. Airport fever screening can thus quickly identify imported dengue cases

Transmission of acute infectious illness among cases of Kawasaki disease and their household members

Background/purposeKawasaki disease (KD) is a disease of unknown cause and the causative agent is most likely to be infectious in nature. To investigate the household transmission pattern of infectious illness and etiology, we thus initiated a prospective case and household study.MethodsWe enrolled KD cases and their household members from February 2004 to September 2008. The KD cases and their household members accepted questionnaire-based interviews of the contact history, signs of infection, and symptoms to check whether clusters of infectious illness occurred.ResultsA total of 142 KD cases and 561 household members were enrolled. Among the 142 KD cases, 136 cases (96%) were typical KD, and six (4%) were atypical KD. Of the 561 household members, 17% were siblings, 46% were parents, 18% were grandparents, and the others were cousins or babysitters. Prior to the onset of their KD illness, 66% (94/142) KD cases had contact with ill household members. On the same day of the onset of KD cases' illness, 4% (6/142) KD cases had household members with illness. After KD cases' disease onset, 70% (100/142) KD cases had at least one other family member with illness. Overall, 61% (343/561) of all the household members had acute infectious illness during KD cases' acute stage, and 92% (130/142) of the families had clusters of infectious illness.ConclusionA total of 66% KD cases had positive contact with ill household members prior to their disease onset and 92% of families had clusters of infectious illness, so KD is strongly associated with infections