Publications -- Zhengyang Zhou

Permanent URI for this collectionhttps://hdl.handle.net/20.500.12503/31844

This collection is limited to articles published under the terms of a creative commons license or other open access publishing agreement since 2016. It is not intended as a complete list of the author's works.

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    Top Alzheimer's disease risk allele frequencies differ in HABS-HD Mexican- versus Non-Hispanic White Americans
    (John Wiley & Sons, Inc., 2024-01-02) Housini, Mohammad; Zhou, Zhengyang; Gutierrez, John; Rao, Sumedha; Jomaa, Rodwan; Subasinghe, Kumudu; Reid, Danielle M.; Silzer, Talisa; Phillips, Nicole; O'Bryant, Sid E.; Barber, Robert C.; Team, HABS-HD Study
    INTRODUCTION: Here we evaluate frequencies of the top 10 Alzheimer's disease (AD) risk alleles for late-onset AD in Mexican American (MA) and non-Hispanic White (NHW) American participants enrolled in the Health and Aging Brain Study-Health Disparities Study cohort. METHODS: Using DNA extracted from this community-based diverse population, we calculated the genotype frequencies in each population to determine whether a significant difference is detected between the different ethnicities. DNA genotyping was performed per manufacturers' protocols. RESULTS: Allele and genotype frequencies for 9 of the 11 single nucleotide polymorphisms (two apolipoprotein E variants, CR1, BIN1, DRB1, NYAP1, PTK2B, FERMT2, and ABCA7) differed significantly between MAs and NHWs. DISCUSSION: The significant differences in frequencies of top AD risk alleles observed here across MAs and NHWs suggest that ethnicity-specific genetic risks for AD exist. Given our results, we are advancing additional projects to further elucidate ethnicity-specific differences in AD.
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    Hypermethylation at CREBBP Is Associated with Cognitive Impairment in a Mexican American Cohort
    (IOS Press, 2023-03-07) Abraham Daniel, Ann; Silzer, Talisa; Sun, Jie; Zhou, Zhengyang; Hall, Courtney; Phillips, Nicole; Barber, Robert C.
    BACKGROUND: The aging Mexican American (MA) population is the fastest growing ethnic minority group in the US. MAs have a unique metabolic-related risk for Alzheimer's disease (AD) and mild cognitive impairment (MCI), compared to non-Hispanic whites (NHW). This risk for cognitive impairment (CI) is multifactorial involving genetics, environmental, and lifestyle factors. Changes in environment and lifestyle can alter patterns and even possibly reverse derangement of DNA methylation (a form of epigenetic regulation). OBJECTIVE: We sought to identify ethnicity-specific DNA methylation profiles that may be associated with CI in MAs and NHWs. METHODS: DNA obtained from peripheral blood of 551 participants from the Texas Alzheimer's Research and Care Consortium was typed on the Illumina Infinium® MethylationEPIC chip array, which assesses over 850K CpG genomic sites. Within each ethnic group (N = 299 MAs, N = 252 NHWs), participants were stratified by cognitive status (control versus CI). Beta values, representing relative degree of methylation, were normalized using the Beta MIxture Quantile dilation method and assessed for differential methylation using the Chip Analysis Methylation Pipeline (ChAMP), limma and cate packages in R. RESULTS: Two differentially methylated sites were significant: cg13135255 (MAs) and cg27002303 (NHWs) based on an FDR p < 0.05. Three suggestive sites obtained were cg01887506 (MAs) and cg10607142 and cg13529380 (NHWs). Most methylation sites were hypermethylated in CI compared to controls, except cg13529380 which was hypomethylated. CONCLUSION: The strongest association with CI was at cg13135255 (FDR-adjusted p = 0.029 in MAs), within the CREBBP gene. Moving forward, identifying additional ethnicity-specific methylation sites may be useful to discern CI risk in MAs.
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    Does abstaining from alcohol in high school moderate intervention effects for college students? Implications for tiered intervention strategies
    (Frontiers Media S.A., 2022-12-20) Tan, Lin; Friedman, Zachary; Zhou, Zhengyang; Huh, David; White, Helene R.; Mun, Eun-Young
    Brief motivational intervention (BMI) and personalized feedback intervention (PFI) are individual-focused brief alcohol intervention approaches that have been proven efficacious for reducing alcohol use among college students and young adults. Although the efficacy of these two intervention approaches has been well established, little is known about the factors that may modify their effects on alcohol outcomes. In particular, high school drinking may be a risk factor for continued and heightened use of alcohol in college, and thus may influence the outcomes of BMI and PFI. The purpose of this study was to investigate whether high school drinking was associated with different intervention outcomes among students who received PFI compared to those who received BMI. We conducted moderation analyses examining 348 mandated students (60.1% male; 73.3% White; and 61.5% first-year student) who were randomly assigned to either a BMI or a PFI and whose alcohol consumption was assessed at 4-month and 15-month follow-ups. Results from marginalized zero-inflated Poisson models showed that high school drinking moderated the effects of PFI and BMI at the 4-month follow-up but not at the 15-month follow-up. Specifically, students who reported no drinking in their senior year of high school consumed a 49% higher mean number of drinks after receiving BMI than PFI at the 4-month follow-up. The results suggest that alcohol consumption in high school may be informative when screening and allocating students to appropriate alcohol interventions to meet their different needs.
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    A nonparametric alternative to the Cochran-Armitage trend test in genetic case-control association studies: The Jonckheere-Terpstra trend test
    (PLOS, 2023-02-03) Manning, Sydney E.; Ku, Hung-Chih; Dluzen, Douglas F.; Xing, Chao; Zhou, Zhengyang
    Identifications of novel genetic signals conferring susceptibility to human complex diseases is pivotal to the disease diagnosis, prevention, and treatment. Genetic association study is a powerful tool to discover candidate genetic signals that contribute to diseases, through statistical tests for correlation between the disease status and genetic variations in study samples. In such studies with a case-control design, a standard practice is to perform the Cochran-Armitage (CA) trend test under an additive genetic model, which suffers from power loss when the model assumption is wrong. The Jonckheere-Terpstra (JT) trend test is an alternative method to evaluate association in a nonparametric way. This study compares the power of the JT trend test and the CA trend test in various scenarios, including different sample sizes (200-2000), minor allele frequencies (0.05-0.4), and underlying modes of inheritance (dominant genetic model to recessive genetic model). By simulation and real data analysis, it is shown that in general the JT trend test has higher, similar, and lower power than the CA trend test when the underlying mode of inheritance is dominant, additive, and recessive, respectively; when the sample size is small and the minor allele frequency is low, the JT trend test outperforms the CA trend test across the spectrum of genetic models. In sum, the JT trend test is a valuable alternative to the CA trend test under certain circumstances with higher statistical power, which could lead to better detection of genetic signals to human diseases and finer dissection of their genetic architecture.
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    A Structural Equation Modeling Approach to Meta-analytic Mediation Analysis Using Individual Participant Data: Testing Protective Behavioral Strategies as a Mediator of Brief Motivational Intervention Effects on Alcohol-Related Problems
    (Springer Nature, 2021-11-12) Huh, David; Li, Xiaoyin; Zhou, Zhengyang; Walters, Scott T.; Baldwin, Scott A.; Tan, Zhengqi; Larimer, Mary E.; Mun, Eun-Young
    This paper introduces a meta-analytic mediation analysis approach for individual participant data (IPD) from multiple studies. Mediation analysis evaluates whether the effectiveness of an intervention on health outcomes occurs because of change in a key behavior targeted by the intervention. However, individual trials are often statistically underpowered to test mediation hypotheses. Existing approaches for evaluating mediation in the meta-analytic context are limited by their reliance on aggregate data; thus, findings may be confounded with study-level differences unrelated to the pathway of interest. To overcome the limitations of existing meta-analytic mediation approaches, we used a one-stage estimation approach using structural equation modeling (SEM) to combine IPD from multiple studies for mediation analysis. This approach (1) accounts for the clustering of participants within studies, (2) accommodates missing data via multiple imputation, and (3) allows valid inferences about the indirect (i.e., mediated) effects via bootstrapped confidence intervals. We used data (N = 3691 from 10 studies) from Project INTEGRATE (Mun et al. Psychology of Addictive Behaviors, 29, 34-48, 2015) to illustrate the SEM approach to meta-analytic mediation analysis by testing whether improvements in the use of protective behavioral strategies mediate the effectiveness of brief motivational interventions for alcohol-related problems among college students. To facilitate the application of the methodology, we provide annotated computer code in R and data for replication. At a substantive level, stand-alone personalized feedback interventions reduced alcohol-related problems via greater use of protective behavioral strategies; however, the net-mediated effect across strategies was small in size, on average.