Biomedical subjects

Wei-Min Chen

Publications and source records attributed to Wei-Min Chen.

12 recordsLinked to original sources

PubMed2026

Diabetes related genetics and outcomes after total pancreatectomy with islet autotransplantation.

CONTEXT: Approximately 20% of patients with chronic pancreatitis achieve insulin independence one year after total pancreatectomy with islet autotransplantation (TPIAT), an outcome associated with younger age and lower pre-transplant HbA1c. The contribution of diabetes-related genetics to TPIAT outcomes is unknown. Genetic risk scores (GRS) are associated with C-peptide levels in type 1 (T1D) and type 2 (T2D) diabetes. OBJECTIVE: To evaluate whether T1D and T2D GRS and partitioned metabolic polygenic scores (PGS) are associated with diabetes before TPIAT and metabolic outcomes one year after transplant. METHODS: We genotyped 318 patients with chronic pancreatitis undergoing TPIAT in the multicenter "Advancing Treatment for Pancreatitis: A Prospective Observational Study of TPIAT" using a global screening array. Regression models assessed associations of T1D- and T2D-GRS and metabolic PGS with diabetes outcomes one year after TPIAT. RESULTS: Participants were 29±17 years old, 61% female, 84% non-Hispanic White, and 13% had diabetes prior to transplant. T2D-GRS was higher among those with pre-TPIAT diabetes (-0.6±0.3 versus -0.8±0.2, p=0.003) and was associated with higher pre-transplant HbA1c (β=0.19 % per 1-SD [95% CI:0.04, 0.33], p = 0.011). Adjusted for genotype-derived ancestry and islet equivalents/kg, the beta-cell PGS was associated with higher insulin dose (β=0.05 units/kg/day per 1-SD, [95%CI:0.01, 0.09], p=0.016) and higher insulin dose adjusted A1c (IDAA1c) (β=0.34[95%CI:0.03, 0.67], p=0.029) 1-year post-transplant. The lipodystrophy PGS was associated with higher IDAA1c (β=0.38 [95%CI:0.06, 0.69], p=0.019) and lower fasting C-peptide (β=-0.09 [95%CI:-0.18, 0], p=0.041) at 1 year. CONCLUSIONS: T2D genetic risk is associated with diabetes prior to TPIAT, and beta cell and lipodystrophy PGS are associated with post-TPIAT diabetes outcomes. Diabetes-related genetics may influence transplantation outcomes and inform metabolic heterogeneity.

C-peptide↗

PubMed2006

In silico method for inferring genotypes in pedigrees.

Our genotype inference method combines sparse marker data from a linkage scan and high-resolution SNP genotypes for several individuals to infer genotypes for related individuals. We illustrate the method's utility by inferring over 53 million SNP genotypes for 78 children in the Centre d'Etude du Polymorphisme Humain families. The method can be used to obtain high-density genotypes in different family structures, including nuclear families commonly used in complex disease gene mapping studies.

Chi-Square Distribution↗

PubMed2006

Heritability of cardiovascular and personality traits in 6,148 Sardinians.

In family studies, phenotypic similarities between relatives yield information on the overall contribution of genes to trait variation. Large samples are important for these family studies, especially when comparing heritability between subgroups such as young and old, or males and females. We recruited a cohort of 6,148 participants, aged 14-102 y, from four clustered towns in Sardinia. The cohort includes 34,469 relative pairs. To extract genetic information, we implemented software for variance components heritability analysis, designed to handle large pedigrees, analyze multiple traits simultaneously, and model heterogeneity. Here, we report heritability analyses for 98 quantitative traits, focusing on facets of personality and cardiovascular function. We also summarize results of bivariate analyses for all pairs of traits and of heterogeneity analyses for each trait. We found a significant genetic component for every trait. On average, genetic effects explained 40% of the variance for 38 blood tests, 51% for five anthropometric measures, 25% for 20 measures of cardiovascular function, and 19% for 35 personality traits. Four traits showed significant evidence for an X-linked component. Bivariate analyses suggested overlapping genetic determinants for many traits, including multiple personality facets and several traits related to the metabolic syndrome; but we found no evidence for shared genetic determinants that might underlie the reported association of some personality traits and cardiovascular risk factors. Models allowing for heterogeneity suggested that, in this cohort, the genetic variance was typically larger in females and in younger individuals, but interesting exceptions were observed. For example, narrow heritability of blood pressure was approximately 26% in individuals more than 42 y old, but only approximately 8% in younger individuals. Despite the heterogeneity in effect sizes, the same loci appear to contribute to variance in young and old, and in males and females. In summary, we find significant evidence for heritability of many medically important traits, including cardiovascular function and personality. Evidence for heterogeneity by age and sex suggests that models allowing for these differences will be important in mapping quantitative traits.

Adolescent↗

PubMed2006

Estimating the power of variance component linkage analysis in large pedigrees.

Variance component linkage analysis is commonly used to map quantitative trait loci (QTLs) in general pedigrees. Large pedigrees are especially attractive for these studies because they provide greater power per genotyped individual than small pedigrees. We propose accurate and computationally efficient methods to calculate the analytical power of variance component linkage analysis that can accommodate large pedigrees. Our analytical power computation involves the approximation of the noncentrality parameter for the likelihood-ratio test by its Taylor expansions. We develop efficient algorithms to compute the second and third moments of the identical by descent (IBD) sharing distribution and enable rapid computation of the Taylor expansions. Our algorithms take advantage of natural symmetries in pedigrees and can accurately analyze many large pedigrees in a few seconds. We verify the accuracy of our power calculation via simulation in pedigrees with 2-5 generations and 2-8 siblings per sibship. We apply this proposed analytical power calculation to 98 quantitative traits in a cohort study of 6,148 Sardinians in which the largest pedigree includes 625 phenotyped individuals. Simulations based on eight representative traits show that the difference between our analytical estimation of the expected LOD score and the average of simulated LOD scores is less than 0.05 (1.5%). Although our analytical calculations are for a fully informative marker locus, in the settings we examined power was similar to what could be attained with a single nucleotide polymorphism (SNP) mapping panel (with >1 SNP/cM). Our algorithms for power analysis together with polygenic analysis are implemented in a freely available computer program, POLY.

Chromosome Mapping↗

PubMed2006

Comparison of the anesthesia profiles between sevoflurane-nitrous oxide and propofol-nitrous oxide conveyed by laryngeal mask airway in patients undergoing ambulatory gynecological surgery.

BACKGROUND: The major purpose of this study is to evaluate and compare the clinical characteristics of sevoflurane-nitrous oxide and propofol-nitrous oxide anesthesias conveyed by laryngeal mask airway (LMA) in patients for gynecological procedures. METHODS: Eighty female patients were randomly assigned to one of the two groups: Group I, inhalational induction at vital capacity with 8% sevoflurane and 67% nitrous oxide in oxygen; Group II, induction with intravenous propofol at 2 mg/kg followed by intravenous infusion at 6 mg/kg/hr. The LMA was inserted after loss of response to jaw thrusting. After successful insertion, in group I anesthesia was maintained with sevoflurane and 67% nitrous oxide in O2 and in group II anesthesia was maintained with propofol at 6 mg/kg/hr and nitrous oxide 67% in oxygen. Anesthetic profiles, including insertion event, postoperative nausea and vomiting, and hemodynamic alterations were compared. RESULTS: Demographic data were comparable in the two groups. After induction, in group II unconsciousness was produced 59 sec shorter than that in group I for placement of LMA. Group I had a higher statistically significant rate of cough upon induction, and by the same token postoperative nausea and vomiting. There were no significant differences in hemodynamic alterations, as well as time to open eyes on command, and time to regain orientation. CONCLUSIONS: Intravenous propofol in combination with 67% nitrous oxide in oxygen technique provided better clinical profiles, compared with sevoflurane-nitrous oxide technique through the use of LMA in gynecological patients undergoing ambulatory short procedures.

Adult↗

PubMed2005

Power and robustness of linkage tests for quantitative traits in general pedigrees.

There are numerous statistical methods for quantitative trait linkage analysis in human studies. An ideal such method would have high power to detect genetic loci contributing to the trait, would be robust to non-normality in the phenotype distribution, would be appropriate for general pedigrees, would allow the incorporation of environmental covariates, and would be appropriate in the presence of selective sampling. We recently described a general framework for quantitative trait linkage analysis, based on generalized estimating equations, for which many current methods are special cases. This procedure is appropriate for general pedigrees and easily accommodates environmental covariates. In this report, we use computer simulations to investigate the power and robustness of a variety of linkage test statistics built upon our general framework. We also propose two novel test statistics that take account of higher moments of the phenotype distribution, in order to accommodate non-normality. These new linkage tests are shown to have high power and to be robust to non-normality. While we have not yet examined the performance of our procedures in the context of selective sampling via computer simulations, the proposed tests satisfy all of the other qualities of an ideal quantitative trait linkage analysis method.

Algorithms↗

PubMed2005

Perinatal findings and molecular cytogenetic analysis of de novo partial trisomy 16q (16q22.1-->qter) and partial monosomy 20q (20q13.3-->qter).

OBJECTIVES: To present the perinatal findings and molecular cytogenetic analysis of de novo partial trisomy 16q and partial monosomy 20q and a review of the literature. CASE AND METHODS: Obstetric ultrasound at 33 weeks' gestation revealed intrauterine growth restriction (IUGR) and dolichocephaly in a 27-year-old primigravid woman. Prenatal cytogenetic diagnosis was not offered because of the late stage of gestation. A 2800-g male baby was delivered at 41 weeks' gestation by cesarean section because of fetal distress. The infant postnatally presented characteristic craniofacial dysmorphism, hypotonia, cleft palate, congenital heart defects, a subependymal cyst, and hypospadia. Cytogenetic analysis revealed an additional material attached to the terminal region of chromosome 20q. The parental karyotypes were normal. Spectral karyotyping (SKY), fluorescence in situ hybridization (FISH), and polymorphic DNA markers were used to investigate the origin of the de novo aberrant chromosome. RESULTS: SKY using 24-color probes, FISH using specific 16p, 16q, 20 centromeric, and 20q telomeric probes, and polymorphic DNA marker analysis confirmed maternal origin of the duplication of distal 16q and the deletion of terminal 20q. Karyotype of the proband was designated as 46,XY.ish der(20)t(16;20)(q22.1;q13.3)(SKY+,16qTEL+,20qTEL-). CONCLUSIONS: Partial trisomy 16q (16q22.1-->qter) and partial monosomy 20q (20q13.3-->qter) may be associated with the perinatal findings of IUGR, dolichocephaly, hypotonia, cleft palate, congenital heart defects, a subependymal cyst, and hypospadia. SKY, FISH, and genetic marker studies help in delineating the parental origin and the regions of the deletion and duplication in the de novo unbalanced translocation.

Abnormalities, Multiple↗

PubMed2004

Quantitative trait linkage analysis by generalized estimating equations: unification of variance components and Haseman-Elston regression.

Two of the major approaches for linkage analysis with quantitative traits in humans include variance components and Haseman-Elston regression. Previously, these were viewed as quite separate methods. We describe a general model, fit by use of generalized estimating equations (GEE), for which the variance components and Haseman-Elston methods (including many of the extensions to the original Haseman-Elston method) are special cases, corresponding to different choices for a working covariance matrix. We also show that the regression-based test of Sham et al. ([2002] Am. J. Hum. Genet. 71:238-253) is equivalent to a robust score statistic derived from our GEE approach. These results have several important implications. First, this work provides new insight regarding the connection between these methods. Second, asymptotic approximations for power and sample size allow clear comparisons regarding the relative efficiency of the different methods. Third, our general framework suggests important extensions to the Haseman-Elston approach which make more complete use of the data in extended pedigrees and allow a natural incorporation of environmental and other covariates.

Algorithms↗

PubMed2004

[The study of magnetic resonance sialography in diagnosing parotid diseases].

OBJECTIVE: To study the feasibility of diagnosing parotid disease with magnetic resonance sialography (MRS) and to select the optimal scanning sequence. METHODS: Twenty-three patients with parotid gland disease and 5 normal adults received sialography using magnetic resonance imaging technique and several sequences (including IR-FSE, FSE, SS-IR-FSE, SS-FSE) were used. After first scanning, the patients were scanned respectively 3 and 10 minutes after buccal application of vitamin C. And MR images of duct obtained. The images of parotid duct system were analysed and evaluated according to their displaying effects. Qualitative diagnosis was made based on MRI and those diagnosis were compared with pathological diagnosis after operation. RESULTS: Images of MR sialography clearly displayed the main duct and its branches of parotid gland and the pathological changes of duct, such as narrow, expanded, stoppage. Of the scanning sequences, IR-FSE was superior to others in manifesting the parotid gland duct (P < 0.05). The performance of images after being given vitamin C did not significantly improve the displaying effect. The accurate rate of qualitative diagnosis was 95.6%. CONCLUSIONS: MR sialography can clearly display the parotid ducts and their pathological changes. The accurate rate of qualitative diagnosis of parotid disease was higher than that X-ray sialography.

Adolescent↗

PubMed2002

The effect of social interactions on circadian self-feeding rhythms in rainbow trout Oncorhynchus mykiss Walbaum.

Circadian feeding rhythms have been revealed in several fish species, but whether or not social interactions influence the expression of the rhythms remains largely unexplored. This paper reported such an exploration in rainbow trout. The experiment was conducted in two consecutive stages in two adjacent insulated rooms. In Stage 1, 40 fish (146.0+/-21.7 g, mean+/-S.D.) were held individually in Room 1. In Stage 2, those 40 fish from Room 1 were distributed into eight groups of five fish according to their previous circadian properties and placed in Room 2. Isolated trout were generally diurnal feeders, but variability among the individuals was evident, with five types of diurnal self-feeding pattern being detected. The influence of social interactions on diel self-feeding pattern in a group was found to be temporary and reversible. The grouping process did not necessarily enhance the expression of circadian self-feeding rhythms, and the dominant individual(s) did not determine the properties of circadian self-feeding rhythms in the group.

Animals↗

PubMed2002

Transmission disequilibrium test with discordant sib pairs when parents are available.

The transmission disequilibrium test (TDT) has been employed to map disease susceptibility loci (DSL), while being immune to the problem of population admixture. The customary TDT test (TDT(D)) was developed for affected child(ren) and their parents and was most often applied to case-parent trios. Recently, the TDT has been extended to the situations when (1) parents are not available but affected and nonaffected sibs from each family are available, (2) unrelated control-parent trios are available for combined analyses with case-parent trios (TDT(DC)), and (3) large pedigrees. For many diseases, affected children in the case-parent trios enlisted into the TDT(D) have unaffected sibs who can be recruited. We present an extension of the TDT by effectively incorporating one unaffected sib of each of the affected children in the case-parent trios into a single analysis (TDT(DS), where DS denotes discordant sib pairs). We have developed a general analytical method for computing the statistical power of the TDT(DS) under any genetic model, the accuracy of which is validated by computer simulations. We compare the power of the TDT(D), TDT(DC), and TDT(DS) under a range of parameter space and genetic models. We find that the TDT(DS) is generally more powerful than the TDT(DC) and TDT(D), particularly when the disease is prevalent (>30%) in the population. The relative power of the TDT(D) and the TDT(DS) largely depends upon the allele frequencies and genetic effects at the DSL, whereas the recombination rate, the degree of linkage disequilibrium, and the marker allele frequencies have little effect. Importantly, the TDT(DS) not only may be more powerful, it also has the advantage of being able to test for segregation distortion that may yield false linkage/association in the TDT(D).

Alleles↗

PubMed2002

[Determination of HLA-DRB1 gene polymorphism by PCR-SBT in Lahu ethnic group of Yunnan, China].

The HLA-DRB1 gene polymorphism in Lahu ethnic of Yunnan, China was the first time investigated using high resolution PCR-SBT method, which is based on sequences of HLA-DRB1 Intron 1 and Intron 2 and with our improvement. From 55 individuals of Lahu ethnic 16 DRB1 alleles were detected. The three most common alleles were HLA-DRB1 * 12021(30.909%), 09012(15.455%), 15011(13.636%), and they covered 60% of the total alleles detected from Lahu ethnic.HLA-DRB1 * 1413, * 11081, * 1312, * 1418, * 1504 were the first time detected in the Chinese, and were very rare in worldwide ethnic groups. With comparison of HLA-DRB1 gene frequencies between various ethnic groups we analyzed the characteristics of HLA-DRB1 gene distribution in worldwide populations,and constructed the phylogenetic tree by Neighbor-joining method and Nei measure of genetic distance. The result showed Lahu ethnic obviously belong to the Chinese South ethnic groups and can't trace its origin from northern groups with the HLA-DRB1 genetic data. The preliminary explanations about the contradiction were given in this paper.

English Abstract↗