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Wen-Chung Lee

Publications and source records attributed to Wen-Chung Lee.

At least 19 recordsLinked to original sources
PubMed2006

Maximal cardiovascular fitness and its correlates in ambulatory hemodialysis patients.

BACKGROUND: Studies focusing on maximal cardiovascular fitness in ambulatory hemodialysis patients are lacking. The main purpose of this study is to look at maximal cardiovascular fitness in ambulatory hemodialysis patients, and the secondary purpose is to look at correlates with such fitness. METHODS: We studied maximal cardiovascular fitness in ambulatory hemodialysis patients and age-matched controls. Correlates of maximal oxygen consumption with functional and physical performance, psychiatric symptoms, cognitive function, quality of life, duration of dialysis therapy, and adequacy of dialysis also were examined. RESULTS: We found ambulatory hemodialysis patients to have 72% to 79% of physical performance and 71% of maximal oxygen consumption compared with age-matched controls. In ambulatory hemodialysis patients, maximal oxygen consumption correlated not only with age and physical performance (the distance walked in a 6-minute walk test, bilateral handgrip strength, and chair-rising time), but also with a psychiatric symptom (losing confidence in oneself) and quality of life (feeling safe in one's daily life). However, multiple regression analysis showed that chair-rising time was the only variable that correlated negatively with maximal oxygen consumption in ambulatory hemodialysis patients. CONCLUSION: Based on the relatively poor maximal cardiovascular fitness in ambulatory hemodialysis patients compared with age-matched controls, an additional fitness training program for these patients is needed.

Aged↗
PubMed2006

Assessing effects of disease genes and gene-environment interactions: the case-spouse design and the counterfactual-control analysis.

BACKGROUND: Assessing joint genetic and environmental contributions to disease risk is the central issue in many genetic epidemiological studies. To characterise the effects of a gene, the case-control study may suffer from the problem of population stratification bias. For a late onset disease, recruiting control subjects into case-parents and case-sibling studies may be difficult. METHODS: Two novel approaches to analysing case-spouse data are introduced: the 1:1 case-counterfactual-control analysis (genotype swapping between the case and their spouse) and the 1:5 case-counterfactual-controls analysis (allele swapping). RESULTS: Both can be implemented using statistical packages that allow matched analysis (the conditional logistic regression) to yield valid estimates of the genotype relative risk, the gene-environment interaction parameter, the gene-sex interaction parameter, and the gene-environment-sex three factor interaction parameter (if desired), if certain assumptions are fulfilled. CONCLUSION: Because of the ease in recruiting subjects, and in collecting and analysing data, this approach makes a convenient tool for gene characterisation.

Bias↗
PubMed2005

A DNA pooling strategy for family-based association studies.

Genome-wide association scans for disease susceptibility genes of complex diseases require genotyping on a massive scale. A DNA pooling strategy for family-based association studies is described, which is robust to population stratification biases and to errors in pooling. It can achieve a statistical efficiency of 0.95 with approximately 1 of 8 or fewer genotyping efforts, and an efficiency of 0.90 with approximately 1 of 16 or fewer efforts compared with individual genotyping. The pooling method described in this article provides a tradeoff between genotyping efforts and subject recruitment efforts.

Alleles↗
PubMed2005

Data-dredging gene-dose analyses in association studies: biases and their corrections.

To examine the joint effect of multiple loci on disease risk, many case-control association studies used "gene-dose analyses." However, some researchers defined high-risk genotypes (or alleles) as those that have higher genotypic (allelic) frequencies in the case group compared with the control group in the study. This will lead to the total number of the "high-risk" genotypes (alleles) tending to be higher for the cases than for the controls as well, even if none of the studied loci were related to the disease. Monte-Carlo simulations done in this study showed that such a "data-dredging" gene-dose analysis could produce grossly biased results. A permutation correction method was proposed which could correct the biases very effectively.

Bias↗
PubMed2004

Case-control association studies with matching and genomic controlling.

Family-based association studies have gained in popularity for mapping disease-susceptibility gene(s) of complex diseases. However, recruiting family controls is often more difficult than recruiting unrelated controls. The author proposes a case-control study, where the possible biases due to population stratification are controlled by matching in the design stage and by genomic controlling in the data-analytic stage. The matching is based on a set of "stratum-delineating variables," such as, race, ethnicity, nationality, ancestry, and birthplace; and the genomic controlling is based on typing a number of null markers across the genome and applying the principle of multiplicative scaling of chi-square distribution. It pays to match carefully to have a higher proportion of correctly matched sets, as computer simulation showed that this would increase the power of the study. If matching is crude, one loses power but still has the correct type I error rate after genomic controlling. Power studies showed that the numbers of affected subjects required for the pair-matched study are comparable to those required by the case-parents design, if the study was conducted in a homogeneous population. As the (control-to-case) matching ratio increases, the number of affected subjects required decreases. With matching ratio tending toward infinity, the number required shrinks roughly by half. The case-control study with matching and genomic controlling frees us from family bondage, and the genetic problem as complicated as mapping genes can now be studied using simple epidemiologic methods.

Case-Control Studies↗
PubMed2004

Mapping disease-susceptibility genes in admixed populations using interval principal component tests.

Family-based association approach for mapping disease-susceptibility genes of complex human diseases is a topical issue in genetic epidemiology. It is well known that admixture between genetically differentiated populations can result in high levels of linkage disequilibrium at loci separated far apart. This property has been capitalized upon to reduce the burden of genotyping in a genomewide association scan. The authors describe a new approach for admixture mapping--the "interval principal component test" (IPCT). The genome is divided into a multitude of non-overlapping "intervals" (with interval length of 10-20 cM) and the information of the markers in the same interval is integrated using the principal component analysis. Monte-Carlo simulation shows that an interval-by-interval scan using IPCT has much better performances than a conventional marker-by-marker scan using the transmission/disequilibrium test (TDT).

Computer Simulation↗
PubMed2004

Body mass index and obesity-related metabolic disorders in Taiwanese and US whites and blacks: implications for definitions of overweight and obesity for Asians.

BACKGROUND: Recommendations based on scanty data have been made to lower the body mass index (BMI; in kg/m(2)) cutoff for obesity in Asians. OBJECTIVE: The goal was to compare relations between BMI and metabolic comorbidity among Asians and US whites and blacks. METHODS: We compared the prevalence rate, sensitivity, specificity, predictive values, and impact fraction of comorbidities at each BMI level and the BMI-comorbidity relations across ethnic groups by using data from the third National Health and Nutrition Examination Survey and the Nutrition and Health Survey in Taiwan (1993-1996). RESULTS: For most BMI values, the prevalences of hypertension, diabetes, and hyperuricemia were higher for Taiwanese than for US whites. In addition, increments of BMI corresponded to higher odds ratios in Taiwanese than in US whites for hypertriglyceridemia (P = 0.01) and hypertension (P = 0.075). BMI-comorbidity relations were stronger in Taiwanese than in US blacks for all comorbidities studied. BMIs of 22.5, 26, and 27.5 were the cutoffs with the highest sum of positive and negative predictive value for Taiwanese, US white, and US black men, respectively. The same order was observed for women. For BMIs >27, >85% of Taiwanese, 66% of whites, and 55% of blacks had at least one of the studied comorbidities. However, a cutoff close to the median of the studied population was often found by maximizing sensitivity and specificity. Reducing BMI from >25 to <25 in persons in the United States could eliminate 13% of the obesity comorbidity studied. The corresponding cutoff in Taiwan is slightly <24. CONCLUSION: These data suggest a possible need to set lower BMI cutoffs for Asians, but where to draw the line is a complex issue.

Adult↗
PubMed2003

Sibling recurrence risk ratio analysis of the metabolic syndrome and its components over time.

BACKGROUND: The purpose of this study was to estimate both cross-sectional sibling recurrence risk ratio (lambdas) and lifetime lambdas for the metabolic syndrome and its individual components over time among sibships in the prospectively followed-up cohorts provided by the Genetic Analysis Workshop 13. Five measures included in the operational criteria of the metabolic syndrome by the Adult Treatment Panel III were examined. A method for estimating sibling recurrence risk with correction for complete ascertainment was used to estimate the numerator, and the prevalence in the whole cohort was used as the denominator of lambdas. RESULTS: Considerable variability in the lambdas was found in terms of different time-points for the cross-sectional definition, the times of fulfilling the criterion for lifetime definition, and different components. Obesity and hyperglycemia had the highest cross-sectional lambdas of the five components. Both components also had the largest slopes in the linear trend of the lifetime lambdas. However, the magnitudes of the lifetime lambdas were similar to that of the mean cross-sectional lambdas, which were <2. The results of nonparametric linkage analysis showed only suggestive evidence of linkage between one marker and lifetime diagnosis of low high-density lipoprotein cholesterol and metabolic syndrome, respectively. CONCLUSION: The lambdas of the metabolic syndrome and its components varies substantially across time, and the lambdas of lifetime diagnosis was not necessarily larger than that of a cross-sectional diagnosis. The magnitude of lambdas does not predict well the maximum LOD score of linkage analysis.

Adolescent↗
PubMed2003

Genetic association studies of adult-onset diseases using the case-spouse and case-offspring designs.

Genetic studies of complex human diseases rely heavily on the family-based association paradigm. However, recruiting parents or siblings can be a difficult task in practice. The author proposes two alternatives, the case-spouse and the case-offspring designs, that are to be analyzed by the mating disequilibrium test. Two assumptions are required: 1) the marker genotype frequencies at conception should be the same for both sexes; and 2) there is no selective attrition of marker allele(s) through gestation and over time. Within this setting, the case-spouse and the case-offspring studies are valid designs, even if only one sex can get the disease, even if cases/spouses/offspring all have different risk factor profiles, and even under assortative mating. If the population is stratified and there is intermarriage between strata, one can type additional null markers across the genome for an admixture correction. The number of families required in a case-spouse design is almost identical to that in a case-parents design. For the case-offspring study with one offspring per family, the number of families should be doubled. Because of the ease in recruiting control subjects, the case-spouse and the case-offspring designs are viable alternatives for genetic association studies of adult-onset diseases.

Adult↗
PubMed2003

Searching for disease-susceptibility loci by testing for Hardy-Weinberg disequilibrium in a gene bank of affected individuals.

The future of genetic studies of complex human diseases will rely more and more on the epidemiologic association paradigm. The author proposes to scan the genome for disease-susceptibility gene(s) by testing for deviation from Hardy-Weinberg equilibrium in a gene bank of affected individuals. A power formula is presented, which is very accurate as revealed by Monte Carlo simulations. If the disease-susceptibility gene is recessive with an allele frequency of < or = 0.5 or dominant with an allele frequency of > or = 0.5, the number of subjects needed by the present method is smaller than that needed by using a case-parents design (using either the transmission/disequilibrium test or the 2-df likelihood ratio test). However, the method cannot detect genes with a multiplicative mode of inheritance, and the validity of the method relies on the assumption that the source population from which the cases arise is in Hardy-Weinberg equilibrium. Thus, it is prone to produce false positive and false negative results. Nevertheless, the method enables rapid gene hunting in an existing gene bank of affected individuals with no extra effort beyond simple calculations.

Epidemiologic Methods↗
PubMed2003

A partial SMR approach to smoothing age-specific rates.

PURPOSE: Age-specific rates are the fundamental measures in epidemiology. For a small population, however, rate estimates can become unstable and the age curve may contain too much random variability to adequately assess the true underlying pattern. A further problem arises when one wishes to log-transform a rate with a zero count in its numerator. The author proposes a simple and non-iterative method to stabilize rates. METHODS: The method, referred to as the "partial SMR approach," relies on finding a standard population with a similar age curve with the study population. Real and simulated data were used to demonstrate its properties. RESULTS: It is found that the choice of the standard is not critical. The method will offset automatically the role of a "dissimilar" standard; and according to the limited simulation studies, the result is still better than no smoothing. The method can also smooth the age curve adaptively, i.e., smoothing to varying degree according to internal stability of each age category. The method is asymptotically unbiased and does not have the zero-count problem. Among the various smoothing methods we have studied, the partial SMR smoothing produces the smallest mean square error and has the highest probability of successful capture of the specific pattern and trend in the age curve. CONCLUSIONS: The partial SMR smoothing is a simple and effective method for smoothing age-specific rates.

Accidents↗
PubMed2003

Potential for gene-gene confounding bias in case-parental control studies.

PURPOSE: To show the potential for gene-gene confounding bias in case-parental control studies. METHODS: The authors quantify the magnitude of gene-gene confounding bias using simple mathematical equations. They also demonstrate the potential problems of such a bias with hypothetical (but realistic) examples. RESULTS: The degree of bias resulting from gene-gene confounding was found to be quite substantial under certain conditions (two genes are very closely linked and/or the study was performed in a recently admixed population). CONCLUSION: In this post-genomic era more and more encounters of the gene-gene confounding will be expected, if the one-gene-at-a-time approach continues to be adopted.

Bias↗
PubMed2003

Admixture mapping using interval transmission/disequilibrium tests.

Family-based studies of genetic association and linkage play a key role in mapping susceptibility genes of complex human diseases. Recent admixture between genetically differentiated populations can result in high levels of linkage disequilibrium even at far apart loci. This has been capitalized upon to reduce the burden of genotyping in a genomewide association scan. Here the authors describe an alternative approach for admixture mapping. The genome is divided into several non-overlapping intervals and the information of the markers in the same interval is integrated--the 'interval transmission/disequilibrium test' (ITDT). This method requires information in the form of the marker allele frequencies in the founding populations. However, computer simulations show that the performances of ITDT are hardly affected by imprecise allele-frequency information. Simulations also show that an interval-by-interval scan using ITDT perform much better than a conventional marker-by-marker scan using TDT, even under conditions where the admixture process occurred over many generations and the individuals in the admixed populations show considerable variation in admixture proportion. Hence the ITDT is a promising new genomewide scan method.

Chromosome Mapping↗
PubMed2002

Standardization using the harmonically weighted ratios: internal and external comparisons.

Standardization of rates is a basic tool for epidemiologists. The most frequently used methods are the 'direct standardization' (with summary index of comparative mortality figure, CMF) and the 'indirect standardization' (with summary index of standardized mortality ratio, SMR). The CMF facilitates a valid comparison between populations or across time periods, yet, it suffers from the problem of instability. By contrast, the SMR is stable and can be used for external comparison. However, it cannot guarantee a valid internal comparison. In this paper, the author proposes a new standardized measure, the 'harmonically weighted ratio' (HWR). The HWR can be used for external as well as internal comparisons--with the assumption of rate-ratio homogeneity, or with heterogeneity but dominance of one population over another. Simulation shows that its performance in terms of pairwise comparisons is the best among the three methods or compares favourably to that of the SMR. The author also examines the behaviours of the HWR when used for hypothesis testing (the 'HWR test'). The HWR can be considered for standardization when the purpose of the standardization is solely for comparison and when the universe of the comparisons can be clearly defined.

Adolescent↗
PubMed2002

Testing for candidate gene linkage disequilibrium using a dense array of single nucleotide polymorphisms in case-parents studies.

The future of genetic studies of complex human diseases will rely more and more on the epidemiologic association paradigm, in particular the use of the transmission/disequilibrium test to detect linkage disequilibrium in a case-parents study. With the rapid progress in genomic studies, many single nucleotide polymorphisms will be identified and genotyped within a very short physical distance. Analyzing multiple single nucleotide polymorphisms within a candidate gene/region with Bonferroni correction for multiple transmission/disequilibrium tests will lead to a conservative test, and hence a power loss. I propose a new method, the "Adaptive PRIncipal COmponent Test" (APRICOT). The method has the following properties: (1) it does not need haplotype information; (2) it is nonparametric-it does not make specific assumptions about the population history or population structure; and (3) the calculation of the test statistic and the determination of its significance level are simple and straightforward. Monte-Carlo simulation reveals that adaptive principal component test maintains the nominal significance level under the null hypothesis of no linkage disequilibrium, even under complex situations of multiple ancestral haplotypes and structured populations. It provides a substantial power advantage over the conventional Bonferroni approach. The adaptive principal component test is a promising method for candidate gene testing using single nucleotide polymorphisms.

Genetic Markers↗