Medicine and Health Sciences Commons^™

Ovarian Cancer Epidemiology, Healthcare Access And Disparities (Orchid): Methodology For A Population-Based Study Of Black, Hispanic And White Patients With Ovarian Cancer, Tomi Akinyemiju, April Deveaux, Lauren Wilson, Anjali Gupta, Ashwini Joshi, Malcolm Bevel, Chioma Omeogu, Onyinye Ohamadike, Bin Huang, Maria Pisu, Margaret Liang, Molly Mcfatrich, Erin Daniell, Laura Jane Fish, Kevin Ward, Maria Schymura, Andrew Berchuck, Arnold L. Potosky

Biostatistics Faculty Publications

INTRODUCTION: Less than 40% of patients with ovarian cancer (OC) in the USA receive stage-appropriate guideline-adherent surgery and chemotherapy. Black patients with cancer report greater depression, pain and fatigue than white patients. Lack of access to healthcare likely contributes to low treatment rates and racial differences in outcomes. The Ovarian Cancer Epidemiology, Healthcare Access and Disparities study aims to characterise healthcare access (HCA) across five specific dimensions-Availability, Affordability, Accessibility, Accommodation and Acceptability-among black, Hispanic and white patients with OC, evaluate the impact of HCA on quality of treatment, supportive care and survival, and explore biological mechanisms that may contribute to …

Incorporating Pathway Information Into Feature Selection Towards Better Performed Gene Signatures, Suyan Tian, Chi Wang, Bing Wang

Biostatistics Faculty Publications

To analyze gene expression data with sophisticated grouping structures and to extract hidden patterns from such data, feature selection is of critical importance. It is well known that genes do not function in isolation but rather work together within various metabolic, regulatory, and signaling pathways. If the biological knowledge contained within these pathways is taken into account, the resulting method is a pathway-based algorithm. Studies have demonstrated that a pathway-based method usually outperforms its gene-based counterpart in which no biological knowledge is considered. In this article, a pathway-based feature selection is firstly divided into three major categories, namely, pathway-level selection, …

Serum Nutrient Levels And Aging Effects On Periodontitis, Jeffrey L Ebersole, Joshua Lambert, Heather Bush, Pinar Emecen Huja, Arpita Basu

Biostatistics Faculty Publications

Periodontal disease damages tissues as a result of dysregulated host responses against the chronic bacterial biofilm insult and approximately 50% of US adults > 30 years old exhibit periodontitis. The association of five blood nutrients and periodontitis were evaluated due to our previous findings regarding a potential protective effect for these nutrients in periodontal disease derived from the US population sampled as part of the National Health and Nutrition Examination Survey (1999–2004). Data from over 15,000 subjects was analyzed for blood levels of cis-β-carotene, β-cryptoxanthin, folate, vitamin D, and vitamin E, linked with analysis of the presence and severity of periodontitis. …

Systems Biology Approach To Late-Onset Alzheimer's Disease Genome-Wide Association Study Identifies Novel Candidate Genes Validated Using Brain Expression Data And Caenorhabditis Elegans Experiments, Shubhabrata Mukherjee, Joshua C. Russell, Daniel T. Carr, Jeremy D. Burgess, Mariet Allen, Daniel J. Serie, Kevin L. Boehme, John S. K. Kauwe, Adam C. Naj, David W. Fardo, Dennis W. Dickson, Thomas J. Montine, Nilufer Ertekin-Taner, Matt R. Kaeberlein, Paul K. Crane

Biostatistics Faculty Publications

Introduction—We sought to determine whether a systems biology approach may identify novel late-onset Alzheimer's disease (LOAD) loci.

Methods—We performed gene-wide association analyses and integrated results with human protein-protein interaction data using network analyses. We performed functional validation on novel genes using a transgenic Caenorhabditis elegans Aβ proteotoxicity model and evaluated novel genes using brain expression data from people with LOAD and other neurodegenerative conditions.

Results—We identified 13 novel candidate LOAD genes outside chromosome 19. Of those, RNA interference knockdowns of the C. elegans orthologs of UBC, NDUFS3, EGR1, and ATP5H were associated with Aβ …

Impact Of Home Visit Capacity On Genetic Association Studies Of Late-Onset Alzheimer's Disease, David W. Fardo, Laura E. Gibbons, Shubhabrata Mukherjee, M. Maria Glymour, Wayne Mccormick, Susan M. Mccurry, James D. Bowen, Eric B. Larson, Paul K. Crane

Biostatistics Faculty Publications

INTRODUCTION—Findings for genetic correlates of late-onset Alzheimer's disease (LOAD) in studies that rely solely on clinic visits may differ from those with capacity to follow participants unable to attend clinic visits.

METHODS—We evaluated previously identified LOAD-risk single nucleotide variants in the prospective Adult Changes in Thought study, comparing hazard ratios (HRs) estimated using the full data set of both in-home and clinic visits (n = 1697) to HRs estimated using only data that were obtained from clinic visits (n = 1308). Models were adjusted for age, sex, principal components to account for ancestry, and additional health indicators.

RESULTS …

Peripheral Inflammation, Apolipoprotein E4, And Amyloid-Β Interact To Induce Cognitive And Cerebrovascular Dysfunction, Felecia M. Marottoli, Yuriko Katsumata, Kevin P. Koster, Riya Thomas, David W. Fardo, Leon M. Tai

Biostatistics Faculty Publications

Cerebrovascular dysfunction is rapidly reemerging as a major process of Alzheimer’s disease (AD). It is, therefore, crucial to delineate the roles of AD risk factors in cerebrovascular dysfunction. While apolipoprotein E4 (APOE4), Amyloid-β (Aβ), and peripheral inflammation independently induce cerebrovascular damage, their collective effects remain to be elucidated. The goal of this study was to determine the interactive effect of APOE4, Aβ, and chronic repeated peripheral inflammation on cerebrovascular and cognitive dysfunction in vivo. EFAD mice are a well-characterized mouse model that express human APOE3 (E3FAD) or APOE4 (E4FAD) and overproduce human Aβ42 via expression of …

Tuberculosis And Risk Of Acute Myocardial Infarction: A Propensity Score-Matched Analysis, Moises A. Huaman, Richard J. Kryscio, Carl J. Fichtenbaum, David Henson, Elizabeth G. Salt, Timothy R. Sterling, Beth A. Garvy

Biostatistics Faculty Publications

Several pathogens have been associated with increased cardiovascular disease (CVD) risk. Whether this occurs with Mycobacterium tuberculosis infection is unclear. We assessed if tuberculosis disease increased the risk of acute myocardial infarction (AMI). We identified patients with tuberculosis index claims from a large de-identified database of ~15 million adults enrolled in a U.S. commercial insurance policy between 2008 and 2010. Tuberculosis patients were 1:1 matched to patients without tuberculosis claims using propensity scores. We compared the occurrence of index AMI claims between the tuberculosis and non-tuberculosis cohorts using Kaplan–Meier curves and Cox Proportional Hazard models. Data on 2026 patients with …

Genetic Association Studies Of Copy-Number Variation: Should Assignment Of Copy Number States Precede Testing?, Patrick Breheny, Prabhakar Chalise, Anthony Batzler, Liewei Wang, Brooke L. Fridley

Biostatistics Faculty Publications

Recently, structural variation in the genome has been implicated in many complex diseases. Using genomewide single nucleotide polymorphism (SNP) arrays, researchers are able to investigate the impact not only of SNP variation, but also of copy-number variants (CNVs) on the phenotype. The most common analytic approach involves estimating, at the level of the individual genome, the underlying number of copies present at each location. Once this is completed, tests are performed to determine the association between copy number state and phenotype. An alternative approach is to carry out association testing first, between phenotype and raw intensities from the SNP array …