Biomedical subjects

Yuan-I Min

Publications and source records attributed to Yuan-I Min.

8 recordsLinked to original sources

PubMed2025

Unveiling the Genetic Landscape of Coronary Artery Disease Through Common and Rare Structural Variants.

BACKGROUND: Genome-wide association studies have identified several hundred susceptibility single nucleotide variants for coronary artery disease (CAD). Despite single nucleotide variant-based genome-wide association studies improving our understanding of the genetics of CAD, the contribution of structural variants (SVs) to the risk of CAD remains largely unclear. METHOD AND RESULTS: We leveraged SVs detected from high-coverage whole genome sequencing data in a diverse group of participants from the National Heart Lung and Blood Institute's Trans-Omics for Precision Medicine program. Single variant tests were performed on 58 706 SVs in a study sample of 11 556 CAD cases and 42 907 controls. Additionally, aggregate tests using sliding windows were performed to examine rare SVs. One genome-wide significant association was identified for a common biallelic intergenic duplication on chromosome 6q21 (P=1.54E-09, odds ratio=1.34). The sliding window-based aggregate tests found 1 region on chromosome 17q25.3, overlapping USP36, to be significantly associated with coronary artery disease (P=1.03E-10). USP36 is highly expressed in arterial and adipose tissues while broadly affecting several cardiometabolic traits. CONCLUSIONS: Our results suggest that SVs, both common and rare, may influence the risk of coronary artery disease.

Humans↗

PubMed2024

The expected polygenic risk score (ePRS) framework: an equitable metric for quantifying polygenetic risk via modeling of ancestral makeup.

Polygenic risk scores (PRSs) depend on genetic ancestry due to differences in allele frequencies between ancestral populations. This leads to implementation challenges in diverse populations. We propose a framework to calibrate PRS based on ancestral makeup. We define a metric called "expected PRS" (ePRS), the expected value of a PRS based on one's global or local admixture patterns. We further define the "residual PRS" (rPRS), measuring the deviation of the PRS from the ePRS. Simulation studies confirm that it suffices to adjust for ePRS to obtain nearly unbiased estimates of the PRS-outcome association without further adjusting for PCs. Using the TOPMed dataset, the estimated effect size of the rPRS adjusting for the ePRS is similar to the estimated effect of the PRS adjusting for genetic PCs. Similarly, we applied the ePRS framework to six cardiovascular-related traits in the All of Us dataset, and the results are consistent with those from the TOPMed analysis. The ePRS framework can protect from population stratification in association analysis and provide an equitable strategy to quantify genetic risk across diverse populations.

Journal Article↗

PubMed2006

Inter-rater agreement of assessed prenatal maternal occupational exposures to lead.

BACKGROUND: Industrial hygienists' assessments of prenatal occupational exposures based on parental job histories is a promising approach for population-based case-control studies of birth defects and other perinatal outcomes. However, evaluations of inter-rater agreement of such assessments have been limited. METHODS: We examined inter-rater agreement of occupational lead exposure assessments of maternal job reports by industrial hygienists in a population-based case-control study of parental occupational lead exposure and low birth weight. A total of 178 jobs with potential exposure to lead during the 6 months before pregnancy to the end of pregnancy were examined. Three industrial hygienists evaluated these jobs independently for exposure to lead including probability of exposure, type of exposure, route of entry, exposure frequency, duration, and intensity. Inter-rater agreement of these assessments beyond chance was evaluated using the kappa statistic (kappa). RESULTS: In general, inter-rater agreement was greater for assessment of direct exposures than assessment of indirect exposures. However, inter-rater agreement varied with the lead exposure metric under consideration, being: 1) fair to good for type of direct exposure (i.e., inorganic or organic), respiratory exposure and frequency of exposure to direct inorganic lead, hours per day of direct (i.e., inorganic or organic), and intensity of direct inorganic exposure; 2) poor for probability and type of indirect exposure (inorganic or organic); and 3) indeterminate for frequency of direct organic exposure, frequency of indirect exposures (organic or inorganic), and intensity of direct exposures (organic or inorganic). CONCLUSION: Retrospective assessment of maternal prenatal exposures to lead by industrial hygienists can provide some reliable metrics of exposure for studies of perinatal outcomes. Reliability studies of such exposure assessments may be useful for: quantifying the reliability of derived exposure metrics; identifying exposure metrics for exposure-outcome analyses; and determining the reliability of prenatal occupational exposures to other agents of interest.

Adult↗

PubMed2006

Risk of immune recovery uveitis in patients with AIDS and cytomegalovirus retinitis.

OBJECTIVE: To evaluate the prevalence of and risk factors for immune recovery uveitis (IRU) in eyes of patients with AIDS and cytomegalovirus (CMV) retinitis. DESIGN: Enrollment data from a 19-clinical center cohort study. PARTICIPANTS: Three hundred seventy-four patients with AIDS and CMV retinitis affecting 539 eyes. METHODS: Patients with AIDS were enrolled at 19 United States AIDS ophthalmology clinics. Data were collected by interview, review of medical records, ophthalmic examination, and phlebotomy. MAIN OUTCOME MEASURE: Immune recovery uveitis. RESULTS: Thirty-six patients (9.6%) were diagnosed with IRU involving 50 eyes. The CD4+ T-cell count of 31 of these had risen by > or =50 cells per microliter above nadir to a level > or = 100 cells per microliter (immune recovery), making up 17.6% of the patients known to have immune recovery after diagnosis of CMV retinitis (95% confidence interval, 12.3%-24.1%). No patients with IRU were observed to have active retinitis or detectable CMV DNA in peripheral blood (P<0.001 and P<0.001 with respect to patients without IRU). Other factors associated with IRU were > or =25% retinal area (odds ratio [OR], 2.72; P = 0.014) or posterior pole involvement with CMV retinitis (odds ratio, 0.43; P = 0.039), treatment with intravitreous injection of cidofovir (OR, 10.6 with respect to eyes never exposed to intravitreous or IV cidofovir; P<0.001), and male gender (OR, 0.26; P = 0.012). More eyes with IRU had visual acuity (VA) of 20/50 or worse (38.0% vs. 26.3%, P = 0.077) relative to eyes without IRU, but the proportions with VA of 20/200 or worse were similar (14.0% vs. 13.8%, P = 0.96). Eyes with IRU more commonly had cystoid macular edema (CME) (45.5% vs. 3.7%, P<0.001) and epiretinal membrane (48.9% vs. 13.3%, P<0.001) than eyes without IRU. CONCLUSIONS: Among eyes of patients with immune recovery, the prevalence of IRU is substantial. Eyes with IRU have a high risk of additional morbidity over and above that seen with CMV retinitis, with several-fold higher risk of CME and epiretinal membrane. Large CMV lesions and use of intravitreous cidofovir are risk factors for IRU.

AIDS-Related Opportunistic Infections↗

PubMed2005

Damage caused by Wegener's granulomatosis and its treatment: prospective data from the Wegener's Granulomatosis Etanercept Trial (WGET).

OBJECTIVE: To analyze damage occurring in patients with Wegener's granulomatosis (WG) enrolled in the WG Etanercept Trial (WGET) and to correlate that damage with disease activity, adverse events, and quality of life. METHODS: The Vasculitis Damage Index (VDI) was applied to all 180 patients at trial entry and every 6 months throughout the trial. Items of damage were analyzed by presumed etiology (i.e., secondary to WG, to therapy, or both) and time of occurrence. Spearman's rank correlation coefficients were calculated between VDI scores and the Birmingham Vasculitis Activity Score for WG (BVAS/WG), frequency of flares, number of adverse events, and the patients' quality-of-life assessments. RESULTS: The mean VDI score was 1.3 at the study enrollment and 1.8 at the end of the trial. This increase was due to damage that occurred despite (or because of) therapy, including visual impairment, hearing loss, nasal blockade, pulmonary fibrosis, hypertension, renal insufficiency, peripheral neuropathy, gonadal failure, and diabetes mellitus. Only 11% of the enrolled patients had not sustained a single VDI item after 1 year of enrollment. When adjusted for baseline VDI, the baseline BVAS/WG correlated moderately well with the VDI score at 1 year (r = 0.20, P = 0.015). Increases in adjusted VDI scores also correlated with the number of adverse events, particularly among patients with limited WG (P = 0.06). CONCLUSION: Damage from both active disease and its treatment remain important problems for patients with WG. Despite the dramatic improvements in patient survival achieved over the last several decades, only a few patients with WG emerge from a period of active disease without sustaining some damage from the disease itself, its treatment, or both. An important measure of future therapeutic approaches will be their ability to reduce the damage accrued over time.

Double-Blind Method↗

PubMed2002

Influence of filgrastim (granulocyte colony-stimulating factor) on human immunodeficiency virus type 1 RNA in patients with cytomegalovirus retinitis.

Filgrastim, or granulocyte colony-stimulating factor, reverses neutropenia associated with human immunodeficiency virus type 1 (HIV-1) and cytomegalovirus (CMV) infections. During a trial of anti-CMV retinitis therapies coadministered with antiretroviral therapy, 2-4 plasma specimens of HIV-1 RNA were collected from 36 HIV-1-infected patients receiving filgrastim to prevent neutropenia and from 36 patients not receiving filgrastim. For both groups, the crude mean and mean rate of change of HIV-1 log(10) RNA levels were similar. Adjustment for covariates (CD4(+) T cell lymphocytes, virus load at enrollment, level of neutropenia and antiretroviral therapy [mainly non-highly active antiretroviral therapy], and anti-CMV therapy during follow-up) resulted in a mean log(10) HIV-1 RNA level for individuals receiving filgrastim versus those not receiving the drug of 5.11 versus 4.87 (P=.12) and respective log mean rates of change per month of -0.08 versus -0.21 (P=.08). This latter difference has borderline statistical significance, which suggests that filgrastim may reduce the decline of HIV-1 RNA loads.

AIDS-Related Opportunistic Infections↗

PubMed2002

HIV and cytomegalovirus viral load and clinical outcomes in AIDS and cytomegalovirus retinitis patients: Monoclonal Antibody Cytomegalovirus Retinitis Trial.

OBJECTIVE: To determine the association of cytomegalovirus (CMV) viremia with mortality and CMV retinitis progression in newly diagnosed and relapsed CMV retinitis. DESIGN: Ancillary study of a randomized, placebo-controlled, phase III clinical trial. PATIENTS: A total of 83 patients with AIDS and CMV retinitis, enrolled during the first phase of the Monoclonal Antibody Cytomegalovirus Retinitis Trial, were administered MSL-109 or placebo as adjuvant therapy for CMV retinitis. MAIN OUTCOME MEASURE(S): Mortality and CMV retinitis progression. RESULTS: Treatment with MSL-109 did not predict either progression of CMV retinitis or mortality. Detection in plasma CMV DNA at baseline predicted mortality, but CMV antigenemia did not. CMV DNA was a better predictor of mortality than a high HIV viral load. Neither CMV DNA nor antigenemia predicted the progression of CMV retinitis. Among newly diagnosed patients, there was a decline in the proportion with detectable CMV viral load and CMV antigenemia in response to anti-CMV therapy. However, there was a rebound in CMV viral load to 25% and CMV antigenemia to 54.6% at 6 months. In relapsed patients, anti-CMV therapy was not associated with a change in the percentage with detectable CMV-DNA or CMV antigenemia over time. CONCLUSION: In patients with AIDS and CMV retinitis, the detection of plasma CMV DNA was associated with a higher risk of mortality than was a high HIV viral load. Anti-CMV therapy provided a transient reduction in CMV viremia in newly diagnosed but not relapsed patients with CMV retinitis. Adjuvant therapy with MSL-109 was ineffective in clearing CMV-DNA and CMV antigen from the plasma.

AIDS-Related Opportunistic Infections↗

PubMed2002

Use of filgrastim as adjuvant therapy in patients with AIDS-related cytomegalovirus retinitis.

BACKGROUND: Neutropenia in AIDS predisposes to bacterial infection. Granulocyte colony-stimulating factor (filgrastim) can reverse neutropenia. OBJECTIVE: To determine the effects of filgrastim on bacterial infections, hospitalization, and mortality in patients with cytomegalovirus retinitis and AIDS. METHODS: Using a person-time analysis, a retrospective cohort study of filgrastim adjuvant therapy in three multicenter clinical trials of anti-cytomegalovirus therapy during the period 1990-1997 measured filgrastim use, bacterial infections, and mortality. RESULTS: Of 719 patients, 379 patients used filgrastim for 31% of the follow-up time. There was an inverse relationship between the 389 confirmed bacterial infections, including 186 bacteremias, and absolute neutrophil counts. Before adjustment for CD4 T-cells counts and antibiotic/antiretroviral therapy, filgrastim was associated with reduced risk of catheter-related bacteremia [relative risk (RR), 0.52; P = 0.02] and repeat bacterial infection (RR, 0.41; P = < 0.01). After adjustment, the RR of catheter-related bacteremia with filgrastim use was decreased (RRadj, 0.69; P = 0.16) and the RR of repeat bacterial infection with filgrastim use was of marginal significance (RRadj, 0.57; P = 0.07), possibly due to the confounding effect of trimethoprim-sulfamethoxazole on all bacteremia (RRadj, 0.55; P = < 0.01). Unrelated to bacteremia, filgrastim use was associated with a 56% reduction in mortality (P < 0.01). CONCLUSIONS: There was a large survival benefit associated with filgrastim use in this study but the reasons for this benefit are unclear. Although a reduction in crude risk of some bacterial infections with filgrastim use was detected, after adjustment for potentially confounding factors these risks were smaller and no longer statistically significant.

AIDS-Related Opportunistic Infections↗