Biomedical subjects

Yi-Hau Chen

Publications and source records attributed to Yi-Hau Chen.

4 recordsLinked to original sources

PubMed2006

Multinomial logistic regression approach to haplotype association analysis in population-based case-control studies.

BACKGROUND: The genetic association analysis using haplotypes as basic genetic units is anticipated to be a powerful strategy towards the discovery of genes predisposing human complex diseases. In particular, the increasing availability of high-resolution genetic markers such as the single-nucleotide polymorphisms (SNPs) has made haplotype-based association analysis an attractive alternative to single marker analysis. RESULTS: We consider haplotype association analysis under the population-based case-control study design. A multinomial logistic model is proposed for haplotype analysis with unphased genotype data, which can be decomposed into a prospective logistic model for disease risk as well as a model for the haplotype-pair distribution in the control population. Environmental factors can be readily incorporated and hence the haplotype-environment interaction can be assessed in the proposed model. The maximum likelihood estimation with unphased genotype data can be conveniently implemented in the proposed model by applying the EM algorithm to a prospective multinomial logistic regression model and ignoring the case-control design. We apply the proposed method to the hypertriglyceridemia study and identifies 3 haplotypes in the apolipoprotein A5 gene that are associated with increased risk for hypertriglyceridemia. A haplotype-age interaction effect is also identified. Simulation studies show that the proposed estimator has satisfactory finite-sample performances. CONCLUSION: Our results suggest that the proposed method can serve as a useful alternative to existing methods and a reliable tool for the case-control haplotype-based association analysis.

Algorithms↗

PubMed2006

HLA typing associated with hepatitis B E antigen seroconversion in children with chronic hepatitis B virus infection: a long-term prospective sibling cohort study in Taiwan.

OBJECTIVE: To conduct a prospective cohort study to clarify the relationship between human leukocyte antigen (HLA) polymorphisms and the seroconversion of hepatitis B e antigen (HBeAg). STUDY DESIGN: In the prospective cohort study, 81 HBeAg-positive children with chronic hepatitis B virus (HBV) infection from 40 unrelated families were recruited and followed-up regularly for a mean period of 17.70 +/- 3.23 years. The association between HLA antigen and the age at HBeAg seroconversion was analyzed using Cox regression model with shared frailties under left truncation and right censorship. RESULTS: HLA-B61 and HLA-DQB1*0503 antigens predicted a higher HBeAg seroconversion rate (relative incidence = 6.17 and 3.22, P = .024 and .017, respectively). Within-family frailty in our sibling cohort study demonstrated a negligible or a low degree of within-family correlation with spontaneous HBeAg seroconversion in each HLA antigen. CONCLUSIONS: HLA class I antigen B61 and class II antigen DQB1*0503 are associated with earlier HBeAg seroconversion in Taiwanese children with chronic HBV infection.

Adolescent↗

PubMed2004

New approach to association testing in case-parent designs under informative parental missingness.

The transmission/disequilibrium test (TDT) and related methods using genotype data on diseased probands and their both parents (triads) have been popular for testing linkage or association between a disease and a candidate gene. The usefulness of the TDT-type approaches lies mainly in their robustness, in the sense that they are valid under population stratification, arbitrary parental genotype distribution, and "informative" parental missingness where the parental missingness may depend on parental genotypes. Recently, a variety of extended TDTs were developed to accommodate parental missingness and to allow for using incomplete triads, including single-offspring-single-parent families (dyads) and single offspring with no parents (monads). However, these methods usually do not preserve the full robustness of the original TDT. In this paper, we propose a new TDT-type approach based on the conditional likelihood of the proband's genotype given the number and, if any, genotypes of the available parents, as well as the proband's phenotype. This new proposal keeps the full robust property of the original TDT. In addition, the new method is very easy to implement, without the need to specify models on parental mating-type probabilities and on parental missingness.

Genetic Linkage↗

PubMed2002

Sample size and optimal designs in stratified comparative trials to establish the equivalence of treatment effects among two ethnic groups.

When a new investigational medicine is intended to be applied to populations with different ethnic backgrounds, a stratified comparative phase III trial using ethnic groups as strata may be conducted to assess the influence of ethnic factors on clinical outcomes of this new medicine. In this paper, based on a binomial model with odds ratio as the measure of the treatment effect, we derive the score test and the associated sample size formula for establishing the equivalence/noninferiority of the treatment effects of a medicine among two ethnic groups. A simplified test together with its sample size formula are also given. Taking into account the sample size, cost, and power of testing, respectively, we derive the optimal design parameters, i.e., the allocation among treatment groups and ethnic groups, based on the simplified test.

Algorithms↗