Biomedical subjects

Yen-Feng Chiu

Publications and source records attributed to Yen-Feng Chiu.

16 recordsLinked to original sources

PubMed2006

Sensitivity and specificity of the Clock Drawing Test, incorporating Rouleau scoring system, as a screening instrument for questionable and mild dementia: scale development.

OBJECTIVE: The objective of this study was to validate the Rouleau scoring system for the Clock Drawing Test (CDT) in northern Taiwan, a non-English speaking area, to increase its generalization by detecting subjects with questionable dementia (QD) from normal controls (NC) and subjects with mild dementia (AD). The system consists of two parts: a 10-point scoring and error types. A cross-sectional design was used. One hundred and sixteen subjects were recruited from a memory disorder clinic (n=40 NC; n=34 QD; n=42 AD). Reliability and validity were estimated, the predictive accuracy was calculated using the receiver operating characteristic (ROC) curve analysis, and the error types were counted. RESULTS: The results indicated that most of the error types committed were conceptual deficiencies and graphic difficulties; more errors were found in the command condition (CDT-command) than in the copy condition (CDT-copy); 15% of the subjects drew smaller clock circles in CDT-command, which did not relate to any other errors. No small clock was found in CDT-copy because a pre-dawn circle was provided. The inter-rater reliability of the Rouleau scoring system was .87 and .83 for the CDT-command and -copy, respectively, while the discriminate accuracy of the scoring system was relatively low in detecting QD vs. NC, QD vs. AD, but somewhat better in distinguishing AD vs. NC groups for the areas under the ROC curves was equal to .72 for the CDT-command, and .73 for the CDT-copy. Visuospatial construction and executive functioning explained the largest score variance of the CDT in both conditions, while depressive symptoms were not significantly associated with the CDT performance. CONCLUSION: The CDT using the Rouleau scoring system has been validated in mild AD subjects in Taiwan; however, to screen for QD sufferers, alternative scoring systems emphasizing hands or combining CDT with different neuropsychological tests such as the Clinical Abilities Screening Instrument are recommended.

Aged↗

PubMed2006

Genome-wide linkage analysis of lipids in nondiabetic Chinese and Japanese from the SAPPHIRe family study.

BACKGROUND: Lipid levels are recognized as major risk factors for coronary heart disease (CHD). Discovery of major loci underlying quantitative lipid traits could help to elucidate the genetics of CHD. METHODS: We performed a genome-wide search for quantitative trait loci linked to lipid phenotypes in 1538 Chinese subjects (509 families) and 625 Japanese subjects (204 families) not taking lipid-lowering medications from the Stanford-Asian Pacific Program in Hypertension and Insulin Resistance (SAPPHIRe) study. The multipoint variance-components method was used to test for linkage between marker loci and each trait by maximum likelihood methods adjusted for effects of age, age(2), gender, body mass index (BMI), smoking, alcohol drinking, physical activity, and field center. RESULTS: The highest logarithm of odds (LOD) score detected was 3.22 for logarithmically transformed HDL-cholesterol on chromosome 12 at 113 cM in Chinese subjects. This score overlaps the positive findings for HDL reported in Mexican Americans (chromosome 12 at 96 cM). Although no strong evidence for linkage was found in Japanese subjects, some modest peaks (LOD score >==1.5) were found in several regions that have been reported in other published genome scans. For example, the Japanese SAPPHIRe peak for HDL (chromosome 1 at 167 cM; LOD = 1.54) was very close to the quantitative trait loci (QTL) for HDL reported in the scan of white American HyperGEN (chromosome 1 at 159.9 cM). CONCLUSIONS: Genome-wide scan for genes influencing lipid phenotypes was conducted and we found significant linkage of HDL to a locus on chromosome 12 in Chinese subjects and no linkage signal exceeding 1.68 was found in the Japanese subjects.

Adult↗

PubMed2006

Comparison of angiogenic factor levels in tumor drainage and peripheral venous blood from colorectal cancer patients.

BACKGROUND: The main objective of this study was to determine whether there was a correlation in the levels of various angiogenesis-related factors between the tumor drainage and peripheral venous blood and whether appraisal of angiogenic factor levels in the tumor drainage venous blood could provide better prognostic information for patients with colorectal cancer than assessment of the peripheral venous blood. METHODS: Plasma levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor, and endostatin were measured and compared in both tumor drainage and peripheral venous blood from 52 patients with colorectal cancer. Plasma levels of angiogenesis-related factors were also correlated with tumor stage and clinical outcomes. RESULTS: The plasma endostatin level was significantly higher in peripheral blood than in tumor drainage venous blood (P < .001). The plasma VEGF level was significantly correlated with plasma endostatin levels (P = .028 in tumor drainage venous blood and P = .002 in peripheral venous blood). In both tumor drainage and peripheral venous blood, the VEGF level (but not the basic fibroblast growth factor or endostatin level) was significantly correlated with tumor stage and disease recurrence. However, in multivariate analysis, only plasma VEGF level in tumor drainage venous blood remained an independent predictor of disease recurrence. CONCLUSIONS: The plasma VEGF level in tumor drainage venous blood provided better prognostic information than that in peripheral venous blood. The plasma endostatin level was paradoxically significantly higher in peripheral than in tumor drainage blood, and this strongly suggests additional sources of endostatin in peripheral blood.

Adult↗

PubMed2005

A comparison in association and linkage genome-wide scans for alcoholism susceptibility genes using single-nucleotide polymorphisms.

We conducted genome-wide linkage scans using both microsatellite and single-nucleotide polymorphism (SNP) markers. Regions showing the strongest evidence of linkage to alcoholism susceptibility genes were identified. Haplotype analyses using a sliding-window approach for SNPs in these regions were performed. In addition, we performed a genome-wide association scan using SNP data. SNPs in these regions with evidence of association (P <or= 0.0001) were identified. We found that the general patterns for nonparametric linkage (NPL) scores from SNP and microsatellite genome scans are fairly consistent; however, the peaks of the NPL scores are mostly higher in the SNP-based scan than those using microsatellite markers, which might be located at different regions. Furthermore, SNPs identified from linkage screens were not so strongly associated with alcoholism (the most significant SNP had a p-value of 0.030) as those identified from association genomic screening (the most significant SNP had a p-value of 2.0 x 10(-8)).

Alcoholism↗

PubMed2005

Multipoint linkage mapping using sibpairs: non-parametric estimation of trait effects with quantitative covariates.

Multipoint linkage analysis using sibpair designs remains a common approach to help investigators to narrow chromosomal regions for traits (either qualitative or quantitative) of interest. Despite its popularity, the success of this approach depends heavily on how issues such as genetic heterogeneity, gene-gene, and gene-environment interactions are properly handled. If addressed properly, the likelihood of detecting genetic linkage and of efficiently estimating the location of the trait locus would be enhanced, sometimes drastically. Previously, we have proposed an approach to deal with these issues by modeling the genetic effect of the target trait locus as a function of covariates pertained to the sibpairs. Here the genetic effect is simply the probability that a sibpair shares the same allele at the trait locus from their parents. Such modeling helps to divide the sibpairs into more homogeneous subgroups, which in turn helps to enhance the chance to detect linkage. One limitation of this approach is the need to categorize the covariates so that a small and fixed number of genetic effect parameters are introduced. In this report, we take advantage of the fact that nowadays multiple markers are readily available for genotyping simultaneously. This suggests that one could estimate the dependence of the generic effect on the covariates nonparametrically. We present an iterative procedure to estimate (1) the genetic effect nonparametrically and (2) the location of the trait locus through estimating functions developed by Liang et al. ([2001a] Hum Hered 51:67-76). We apply this new method to the linkage study of schizophrenia to illustrate how the onset ages of each sibpair may help to address the issue of genetic heterogeneity. This analysis sheds new light on the dependence of the trait effect on onset ages from affected sibpairs, an observation not revealed previously. In addition, we have carried out some simulation work, which suggests that this method provides accurate inference for estimating the location of quantitative trait loci.

Algorithms↗

PubMed2005

Multipoint linkage disequilibrium mapping using case-control designs.

Case-control study has been and continues to be one of the most popular designs in epidemiology. More recently, this design has been adopted to test for candidate genes when searching for disease genetic etiology. In this report, we present a multipoint linkage disequilibrium (LD) mapping approach with the focus on estimating the location of the target trait locus. It builds upon a representation, which shows that the difference between a case and a control in probabilities of carrying the target allele of a marker is proportional to that of the trait locus and that the proportionality factor is simply a measure of LD between the trait locus and the marker. Our method has the desired properties that (1) there is no need to specify phases of genotypic data with multiple markers, (2) it provides an estimate of location of the disease locus along with sampling uncertainty to help investigators to narrow chromosomal regions, and (3) a single test statistic is provided to test for LD in the framed region rather than testing the hypothesis one marker at a time. Our simulation work suggests that the proposed method performs well in terms of bias and coverage probability. Extension of the proposed method to account for confounding and genetic heterogeneity is discussed. We apply the proposed method to a published case-control data set for cystic fibrosis.

Alleles↗

PubMed2005

Risk factors of massive bleeding related to pancreatic leak after pancreaticoduodenectomy.

BACKGROUND: Most pancreatic leaks after pancreaticoduodenectomy were initially treated conservatively, and for the most part, they were self-limiting and closed spontaneously. But in a few patients, hemorrhage occurred 1 to 3weeks postoperatively and remained a fatal complication after pancreaticoduodenectomy. STUDY DESIGN: To identify possible risk factors for massive bleeding, the medical records of 402 patients who had pancreaticoduodenectomies were reviewed for leak complications and analyzed for associations between the occurrence of massive bleeding and preoperative, intraoperative, postoperative, and pathologic parameters. RESULTS: In univariate logistic regression analysis, infectious clinical signs (p=0.021, odds ratio [OR]=7.06, 95% CI=1.34, 37.12) and bile in the drainage fluid (p=0.036, OR=5.89, 95% CI=1.13, 30.86) were associated with the risk of developing massive hemorrhage. This combination provided the highest estimate of massive bleeding after pancreatic leak (p=0.005, OR=8.57, 95% CI=1.92, 38.35). CONCLUSIONS: Both infectious clinical signs and bile content in the drainage fluid considerably increase the risk of massive bleeding after pancreatic leak. Close observation of patients with these ominous signs is warranted.

Adolescent↗

PubMed2005

Impact of apolipoprotein A5 polymorphisms on insulin sensitivity and beta-cell function.

OBJECTIVES: Alternation in lipid metabolism can affect both insulin sensitivity and beta-cell function. Apolipoprotein A5 (APOA5) is an important determinant of lipid metabolism. The impact of the APOA5 gene on insulin sensitivity and beta-cell function has not been examined. METHODS: We examined the influence of 2 amino acid polymorphisms (V150M and G182C) in the APOA5 gene on insulin sensitivity and beta-cell function in 67 glucose-tolerant white subjects. Insulin sensitivity index (ISI) and first- and second-phase insulin responses (1stIR and 2ndIR) were assessed using a hyperglycemic clamp technique. RESULTS: We identified 59 VV and 8 VM subjects, and none had either the GC or CC genotype. Although no association was found with fasting lipid profile and plasma glucose concentrations during oral glucose tolerance test, the V150M was associated with higher 1stIR (P = 0.0010) and 2ndIR (P = 0.0016) and lower ISI (P = 0.0135). The associations of this polymorphism with 1stIR (P = 0.0081) and 2ndIR (P = 0.0087) were independent of sex, age, and body mass index, but not ISI. CONCLUSIONS: The V150M polymorphism had an independent influence on 1stIR and 2ndIR. Although the biologic consequence of this polymorphism remains to be determined, the V150M polymorphism in the APOA5 gene is a genetic marker for beta-cell function.

Adult↗

PubMed2005

An autosomal genome-wide scan for loci linked to pre-diabetic phenotypes in nondiabetic Chinese subjects from the Stanford Asia-Pacific Program of Hypertension and Insulin Resistance Family Study.

Type 2 diabetes is a complex disease involving both genetic and environmental components. Abnormalities in insulin secretion and insulin action usually precede the development of type 2 diabetes and can serve as good quantitative measures for genetic mapping. We therefore undertook an autosomal genomic search to locate the quantitative trait locus (QTL) linked to these traits in 1,365 nondiabetic Chinese subjects from 411 nuclear families. Residuals of these log-transformed quantitative traits were analyzed in multipoint linkage analysis using a variance-components approach. The most significant QTL for fasting insulin, which coincides with the QTL for homeostasis model assessment of insulin resistance, was located at 37 cM on chromosome 20, with a maximum empirical logarithm of odds (LOD) score of 3.01 (empirical P = 0.00006) when adjusted for age, sex, BMI, antihypertensive medications, recruitment centers, and environmental factors. In the same region, a QTL for fasting glucose was identified at 51 cM, with an empirical LOD score of 2.03 (empirical P = 0.0012). There were other loci with maximum empirical LOD scores >or=1.29 located on chromosomes 1q, 2p, 5q, 7p, 9q, 10p, 14q, 18q, and 19q for different diabetes-related traits. These loci may harbor genes that regulate glucose homeostasis either independently or via interactions of the genes within these regions.

Asian People↗

PubMed2004

Conditional multipoint linkage analysis using affected sib pairs: an alternative approach.

Recently, Liang et al. ([2001b] Genet. Epidemiol. 21:105-122) proposed a conditional approach to assess linkage evidence on the target region by incorporating linkage information from an unlinked (reference) region using allele shared IBD (identity-by-decent) from affected sib pairs. This is carried out by conditioning on the IBD sharing value at the estimated trait locus of the reference region. Since markers considered are typically non-fully informative, the IBD sharing at each marker needs to be estimated (or imputed). In this report, we propose an alternative approach to deal with the IBD sharing in the reference region. This new approach makes full use of the observed data without having to categorize the imputed IBD sharing as needed in Liang et al. ([2001b] Genet. Epidemiol. 21:105-122). We compare these two approaches by simulating data from a variety of two-locus models including heterogeneity, additive and multiplicative with either fully informative markers or non-fully informative markers. The performance of both approaches is quite comparable showing consistent estimates of the trait locus and key genetic parameters.

Alleles↗

PubMed2004

Factors affecting increasing radiation dose for mammography in North Carolina from 1997 through 2001: an analysis of Food and Drug Administration annual surveys.

RATIONALE AND OBJECTIVES: To determine which factors affected the increase in average glandular dose recorded at the annual US Food and Drug Administration Mammography Quality Standards Act inspections of mammography equipment in North Carolina from 1997 to 2001. MATERIALS AND METHODS: Average glandular dose, HVL, kVp, ambient light, luminance, equipment age, processing speed, and system speed for every mammography unit at all facilities in the state were collected by state inspectors. A mixed-effect model was used to assess the average changes of glandular dose over time and to identify the factors associated with these changes. RESULTS: There was a statistically significant increase in the average glandular dose in North Carolina in 1999, 2000, and 2001 when compared with the baseline year of 1997. Factors that were statistically significantly linked to this effect were changes in kVp, processing speed, and system speed. CONCLUSION: Average glandular dose for mammography has recently increased in North Carolina. This change is likely caused by changes in screen-film products and processing techniques.

Annual Reports as Topic↗

PubMed2004

Biethnic comparisons of autosomal genomic scan for loci linked to plasma adiponectin in populations of Chinese and Japanese origin.

Adiponectin is secreted by adipocytes and is thought to have insulin-sensitizing and antiatherogenic effects. Two previous genome scans for plasma adiponectin have identified different regions for European and Pima Indian populations. We here present multipoint linkage analysis of adiponectin levels using a variance-components model for 1007 siblings (from 360 nuclear families) of Chinese origin and 352 siblings (from 147 nuclear families) of Japanese origin. We found heritability for adiponectin concentrations was 0.70 for Chinese and 0.48 for Japanese. Autosomal genome scan was performed using microsatellite markers span at an interval of approximately 10 cM. Suggestive linkage of adiponectin, after adjusting for age and sex, was found on chromosome 15 at 39 cM (maximal LOD score = 3.19, P = 6.3 x 10(-5)) for Chinese; and on chromosome 18 at 28 cM (maximal LOD score = 2.40, P = 4.4 x 10(-4)) for Japanese. There were tentative loci of weak linkage on chromosomes 3, 18, and 20 in Japanese. We provide novel loci on chromosomes 15, 18, and 20 and confirm a region on chromosome 3 as reported in Pima Indians, which may influence differentially on circulating adiponectin concentrations in Chinese and Japanese populations. Further fine mapping of these regions will help to identify the gene(s) that might affect adiponectin levels.

Adiponectin↗

PubMed2003

Familial aggregation of psychotic symptoms in a replication set of 69 bipolar disorder pedigrees.

We found evidence previously of familial aggregation of psychotic symptoms in 65 bipolar disorder pedigrees. This finding, together with prior evidence from clinical, family, neurobiological, and linkage studies, suggested that psychotic bipolar disorder may delineate a valid subtype. We sought to replicate this finding in 69 new bipolar disorder pedigrees. The presence of psychotic symptoms, defined as hallucinations or delusions, during an affective episode was compared in families of 46 psychotic and 23 non-psychotic bipolar I probands ascertained at Johns Hopkins for the NIMH Bipolar Disorder Genetics Initiative. There were 198 first-degree relatives with major affective disorder including 90 with bipolar I disorder. Significantly more psychotic proband families than non-psychotic proband families (76% vs. 48%) contained at least one affected relative with psychotic symptoms. Psychotic symptoms occurred in 35% of relatives of psychotic probands and in 22% of relatives of non-psychotic probands (P = 0.10). Both psychotic affective disorder generally and psychotic bipolar I disorder clustered significantly in families. These results are consistent with our prior report although the magnitude of the predictive effect of a psychotic proband is less in the replication families. Our findings provide modest support for the validity of psychotic bipolar disorder as a subtype of bipolar disorder. This clinically defined subtype may prove more homogeneous than the disorder as a whole at the level of genetic etiology and of neuropathology/pathophysiology. Families with this subtype should be used to search for susceptibility genes common to bipolar disorder and schizophrenia, and for biological markers that may be shared with schizophrenia.

Bipolar Disorder↗

PubMed2003

Multipoint affected sibpair linkage methods for localizing susceptibility genes of complex diseases.

Recently, Liang et al. ([2001] Hum. Hered. 51:64-78) proposed a general multipoint linkage method for estimating the chromosomal position of a putative susceptibility locus. Their technique is computationally simple and does not require specification of penetrance or a mode of inheritance. In complex genetic diseases, covariate data may be available which reflect etiologic or locus heterogeneity. We developed approaches to incorporating covariates into the method of Liang et al. ([2001] Hum. Hered. 51:64-78) with particular attention to exploiting age-at-onset information. The results of simulation studies, and a worked data example using a family data set ascertained through probands with schizophrenia, suggest that utilizing covariate information can yield substantial efficiency gains in localizing susceptibility genes.

Age of Onset↗

PubMed2003

Does biopsy, aspiration or six-month follow-up of a false-positive mammogram reduce future screening or have large psychosocial effects?

RATIONALE AND OBJECTIVES: To determine the differences in the psychosocial effects and future mammography screening behavior between women who had an abnormal mammogram followed either by percutaneous or open surgical breast biopsy or cyst aspiration, or by short-term follow-up mammography to provide insight to radiologists making decisions regarding work-up. MATERIALS AND METHODS: A structured interview was administered to women who recently had abnormal mammograms, leading to biopsy or aspiration (170 cases), or short-term follow-up (176 controls), by telephone within a month of the eligibility event and again approximately 15 months later. Information was collected on perceived pain/discomfort, interactions with medical staff, emotional impact, general breast cancer knowledge, patient attitude towards early diagnosis of breast cancer, perceived risk, previous and intended screening behavior, and subjective health status. Wilcoxon rank sum statistical test was used to compare the two groups at the time of both interviews. RESULTS: Cases and controls had similar demographics. There were no significant differences in the examined psychosocial effects and reported intention to undergo future screening mammography between cases and controls. The overwhelming majority of both cases and controls both reported intention to and underwent routine screening 15 months after the eligibility event. CONCLUSION: Undergoing a biopsy, cyst aspiration, or 6-month follow-up after a positive mammogram does not have large psychosocial effects, nor does it deter women from undergoing screening mammography in the future.

Adult↗

PubMed2002

Multipoint linkage detection in the presence of heterogeneity.

Linkage heterogeneity is common for complex diseases. It is well known that loss of statistical power for detecting linkage will result if one assumes complete homogeneity in the presence of linkage heterogeneity. To this end, Smith (1963, Annals of Human Genetics 27, 175-182) proposed an admixture model to account for linkage heterogeneity. It is well known that for this model, the conventional chi-squared approximation to the likelihood ratio test for no linkage does not apply even when the sample size is large. By dealing with nuclear families and one marker at a time for genetic diseases with simple modes of inheritance, score-based test statistics (Liang and Rathouz, 1999, Biometrics 55, 65-74) and likelihood-ratio-based test statistics (Lemdani and Pons, 1995, Biometrics 51, 1033-1041) have been proposed which have a simple large-sample distribution under the null hypothesis of linkage. In this paper, we extend their work to more practical situations that include information from multiple markers and multi-generational pedigrees while allowing for a class of general genetic models. Three different approaches are proposed to eliminate the nuisance parameters in these test statistics. We show that all three approaches lead to the same asymptotic distribution under the null hypothesis of no linkage. Simulation results show that the proposed test statistics have adequate power to detect linkage and that the performances of these two classes of test statistics are quite comparable. We have applied the proposed method to a family study of asthma (Barnes et al., 1996), in which the score-based test shows evidence of linkage with p-value <0.0001 in the region of interest on chromosome 12. Additionally, we have implemented this score-based test within the frequently used computer package GENEHUNTER.

Journal Article↗