Biostatistics Commons^™

Inter-Relationships Linking Probability Of Becoming A Case Of Nicotine Dependence With Frequency Of Tobacco Cigarette Smoking, Olga A. Vsevolozhskaya, James C. Anthony

Biostatistics Faculty Publications

INTRODUCTION: Once smoking starts, some tobacco cigarette smokers (TCS) can make very rapid transitions into tobacco dependence syndromes (TCD). With adjustment for smoking frequency, we posit female excess risk for this rapid-onset TCD. In a novel application of functional analysis for tobacco research, we estimate four Hill function parameters and plot TCD risk against a gradient of smoking frequency, as observed quite soon after smoking onset.

METHODS: In aggregate, the National Surveys of Drug Use and Health, 2004-2013, identified 1546 newly incident TCS in cross-sectional research, each with standardized TCD assessment.

RESULTS: Hill function estimates contradict our apparently over-simplistic hypothesis. …

On Combining Family- And Population- Based Sequencing Data, Yuriko Katsumata, David W. Fardo

Biostatistics Faculty Publications

Several statistical group-based approaches have been proposed to detect effects of variation within a gene for each of the population- and family-based designs. However, unified tests to combine gene-phenotype associations obtained from these 2 study designs are not yet well established. In this study, we investigated the efficient combination of population-based and family-based sequencing data to evaluate best practices using the Genetic Analysis Workshop 19 (GAW19) data set. Because one design employed whole genome sequencing and the other whole exome sequencing, we examined variants overlapping both data sets. We used the family-based sequence kernel association test (famSKAT) to analyze the …

Causal Effect Estimation In Sequencing Studies: A Bayesian Method To Account For Confounder Adjustment Uncertainty, Chi Wang, Jinpeng Liu, David W. Fardo

Biostatistics Faculty Publications

Estimating the causal effect of a single nucleotide variant (SNV) on clinical phenotypes is of interest in many genetic studies. The effect estimation may be confounded by other SNVs as a result of linkage disequilibrium as well as demographic and clinical characteristics. Because a large number of these other variables, which we call potential confounders, are collected, it is challenging to select and adjust for the variables that truly confound the causal effect. The Bayesian adjustment for confounding (BAC) method has been proposed as a general method to estimate the average causal effect in the presence of a large number …

Comparing Performance Of Non-Tree-Based And Tree-Based Association Mapping Methods, Katherine L. Thompson, David W. Fardo

Statistics Faculty Publications

A central goal in the biomedical and biological sciences is to link variation in quantitative traits to locations along the genome (single nucleotide polymorphisms). Sequencing technology has rapidly advanced in recent decades, along with the statistical methodology to analyze genetic data. Two classes of association mapping methods exist: those that account for the evolutionary relatedness among individuals, and those that ignore the evolutionary relationships among individuals. While the former methods more fully use implicit information in the data, the latter methods are more flexible in the types of data they can handle. This study presents a comparison of the 2 …

Pleiotropic Effects Of Csf Levels Of Alzheimer’S Disease Proteins, Olga A. Vsevolozhskaya, Ilai Keren, David W. Fardo, Dmitri V. Zaykin

Biostatistics Presentations

Cerebrospinal fluid (CSF) analytes harbor potential as diagnostic biomarkers for Alzheimer’s Disease (AD). Quantitative measures of CSF proteins comprise a set of often highly correlated endophenotypes that have previously shown promise in genetic analyses (Cruchaga et al., 2013; Kauwe et al., 2014). Pleiotropic impact of genetic variations on this set may provide additional insights into AD pathology at its earliest stages. To determine which specific endophenotypes are pleiotropic, one can employ methods based on the reverse regression of genotype on phenotypes. Recently, we proposed a method based functional linear models (Vsevolozhskaya et al, 2016) that utilizes reverse regression and simultaneously …

Using Low-Dose Radiation To Potentiate The Effect Of Induction Chemotherapy In Head And Neck Cancer: Results Of A Prospective Phase 2 Trial, Susanne M. Arnold, Mahesh Kudrimoti, Emily V. Dressler, John F. Gleason, Natalie L. Silver, William F. Regine, Joseph Valentino

Internal Medicine Faculty Publications

Purpose: Low-dose fractionated radiation therapy (LDFRT) induces effective cell killing through hyperradiation sensitivity and potentiates effects of chemotherapy. We report our second investigation of LDFRT as a potentiator of the chemotherapeutic effect of induction carboplatin and paclitaxel in locally advanced squamous cell cancer of the head and neck (SCCHN).

Experimental Design: Two cycles of induction therapy were given every 21 days: paclitaxel (75 mg/m²) on days 1, 8, and 15; carboplatin (area under the curve 6) day 1; and LDFRT 50 cGy fractions (2 each on days 1, 2, 8, and 15). Objectives included primary site complete response …

Weighted-Samgsr: Combining Significance Analysis Of Microarray-Gene Set Reduction Algorithm With Pathway Topology-Based Weights To Select Relevant Genes, Suyan Tian, Howard H. Chang, Chi Wang

Biostatistics Faculty Publications

Background: It has been demonstrated that a pathway-based feature selection method that incorporates biological information within pathways during the process of feature selection usually outperforms a gene-based feature selection algorithm in terms of predictive accuracy and stability. Significance analysis of microarray-gene set reduction algorithm (SAMGSR), an extension to a gene set analysis method with further reduction of the selected pathways to their respective core subsets, can be regarded as a pathway-based feature selection method.

Methods: In SAMGSR, whether a gene is selected is mainly determined by its expression difference between the phenotypes, and partially by the number of pathways to …

Diffuse Optical Measurements Of Head And Neck Tumor Hemodynamics For Early Prediction Of Chemoradiation Therapy Outcomes, Lixin Dong, Mahesh Kudrimoti, Daniel Irwin, Li Chen, Sameera Kumar, Yu Shang, Chong Huang, Ellis L. Johnson, Scott D. Stevens, Brent J. Shelton, Guoqiang Yu

Biomedical Engineering Faculty Publications

This study used a hybrid near-infrared diffuse optical instrument to monitor tumor hemodynamic responses to chemoradiation therapy for early prediction of treatment outcomes in patients with head and neck cancer. Forty-seven patients were measured once per week to evaluate the hemodynamic status of clinically involved cervical lymph nodes as surrogates for the primary tumor response. Patients were classified into two groups: complete response (CR) (n = 29) and incomplete response (IR) (n = 18). Tumor hemodynamic responses were found to be associated with clinical outcomes (CR/IR), wherein the associations differed depending on human papillomavirus (HPV-16) status. In HPV-16 …

Left And Right Ventricular Dyssynchrony And Strains From Cardiovascular Magnetic Resonance Feature Tracking Do Not Predict Deterioration Of Ventricular Function In Patients With Repaired Tetralogy Of Fallot, Linyuan Jing, Gregory J. Wehner, Jonathan D. Suever, Richard Charnigo, Sudad Alhadad, Evan Stearns, Dimitri Mojsejenko, Christopher M. Haggerty, Kelsey Hickey, Anne Marie Valente, Tal Geva, Andrew J. Powell, Brandon K. Fornwalt

Saha Cardiovascular Research Center Faculty Publications

Background: Patients with repaired tetralogy of Fallot (rTOF) suffer from progressive ventricular dysfunction decades after their surgical repair. We hypothesized that measures of ventricular strain and dyssynchrony would predict deterioration of ventricular function in patients with rTOF.

Methods: A database search identified all patients at a single institution with rTOF who underwent cardiovascular magnetic resonance (CMR) at least twice, > 6 months apart, without intervening surgical or catheter procedures. Seven primary predictors were derived from the first CMR using a custom feature tracking algorithm: left (LV), right (RV) and inter-ventricular dyssynchrony, LV and RV peak global circumferential strains, and LV and …

Diabetes Is Associated With Cerebrovascular But Not Alzheimer's Disease Neuropathology, Erin L. Abner, Peter T. Nelson, Richard J. Kryscio, Frederick A. Schmitt, David W. Fardo, Randall L. Woltjer, Nigel J. Cairns, Lei Yu, Hiroko H. Dodge, Chengjie Xiong, Kamal Masaki, Suzanne L. Tyas, David A. Bennett, Julie A. Schneider, Zoe Arvanitakis

Sanders-Brown Center on Aging Faculty Publications

INTRODUCTION: The relationship of diabetes to specific neuropathologic causes of dementia is incompletely understood.

METHODS: We used logistic regression to evaluate the association between diabetes and infarcts, Braak neurofibrillary tangle stage, and neuritic plaque score in 2365 autopsied persons. In a subset of >1300 persons with available cognitive data, we examined the association between diabetes and cognition using Poisson regression.

RESULTS: Diabetes increased odds of brain infarcts (odds ratio [OR] = 1.57, P < .0001), specifically lacunes (OR = 1.71, P < .0001), but not Alzheimer's disease neuropathology. Diabetes plus infarcts was associated with lower cognitive scores at end of life than infarcts or diabetes alone, and diabetes plus high level of Alzheimer's neuropathologic changes was associated with lower mini-mental state examination scores than the pathology alone.

DISCUSSION: This study supports the conclusions that diabetes increases the risk of cerebrovascular but not Alzheimer's disease pathology, and at least some of diabetes' relationship to …

Dealing With Zero-Numerators In Estimating Drug-Dependence Chances: A Bayesian Approach, Olga A. Vsevolozhskaya, Fernando A. Wagner, James C. Anthony

Biostatistics Presentations

Aims: At CPDD 2015, we applied parametric Hill functions to estimate the probability of drug dependence in relation to the duration of drug-taking experience. A problem we and others have encountered in the estimation of risk of becoming a drug dependence case is an observed point estimate of zero – the so-called “zero-numerator problem.” This problem can be easily observed in certain low risk subgroups even when the sample is large (e.g., the incidence of heroin dependence among 12 year old newly incident heroin users) or with small subgroup sample sizes. In these instances, tan observed zero point estimate …

Partner Interfering Behaviors Affecting Cancer Quality Of Life, Ann L. Coker, Diane R. Follingstad, Lisandra S. Garcia, Heather M. Bush

Obstetrics and Gynecology Faculty Publications

Objective: Because partners are an important and unpaid resource in cancer care, understanding how destructive, controlling or interfering partner behaviors influence women's cancer care may be particularly relevant for health care providers seeking to provide cancer care and enhance recovery. Using a new measure of partner interfering behaviors in cancer care (PIB-C), we investigated whether women with a recent cancer diagnosis who additionally endorsed any PIB-C would report (a) more symptoms of depression and stress, and (b) lower Functional Assessment of Cancer Therapy (FACT-G) and lower Functional Assessment of Chronic Illness Therapy-Spiritual Well-being (FACIT-SP) scale scores indicating poorer quality of …

Uncovering Local Trends In Genetic Effects Of Multiple Phenotypes Via Functional Linear Models, Olga A. Vsevolozhskaya, Dmitri V. Zaykin, David A. Barondess, Xiaoren Tong, Sneha Jadhav, Qing Lu

Biostatistics Faculty Publications

Recent technological advances equipped researchers with capabilities that go beyond traditional genotyping of loci known to be polymorphic in a general population. Genetic sequences of study participants can now be assessed directly. This capability removed technology-driven bias toward scoring predominantly common polymorphisms and let researchers reveal a wealth of rare and sample-specific variants. Although the relative contributions of rare and common polymorphisms to trait variation are being debated, researchers are faced with the need for new statistical tools for simultaneous evaluation of all variants within a region. Several research groups demonstrated flexibility and good statistical power of the functional linear …

Correlation Of Maximal Inspiratory Pressure To Transdiaphragmatic Twitch Pressure In Intensive Care Unit Patients, Gerald S. Supinski, Philip M. Westgate, Leigh Ann Callahan

Internal Medicine Faculty Publications

Background: Respiratory muscle weakness contributes to respiratory failure in ICU patients. Unfortunately, assessment of weakness is difficult since the most objective test, transdiaphragmatic pressure in response to phrenic nerve stimulation (PdiTw), is difficult to perform. While most clinicians utilize maximum inspiratory pressure (Pimax) to assess strength, the relationship of this index to PdiTw has not been evaluated in a large ICU population. The purpose of the present study was to assess both PdiTw and Pimax in ICU patients to determine how these indices correlate with each other, what factors influence these indices, and how well these indices predict outcomes.

Methods: …

Motorcycle Helmet Effectiveness In Reducing Head, Face And Brain Injuries By State And Helmet Law, Cody S. Olsen, Andrea M. Thomas, Michael Singleton, Anna M. Gaichas, Tracy J. Smith, Gary A. Smith, Justin Peng, Michael J. Bauer, Ming Qu, Denise Yeager, Timothy Kerns, Cynthia Burch, Lawrence J. Cook

Biostatistics Faculty Publications

Background: Despite evidence that motorcycle helmets reduce morbidity and mortality, helmet laws and rates of helmet use vary by state in the U.S.

Methods: We pooled data from eleven states: five with universal laws requiring all motorcyclists to wear a helmet, and six with partial laws requiring only a subset of motorcyclists to wear a helmet. Data were combined in the Crash Outcome Data Evaluation System's General Use Model and included motorcycle crash records probabilistically linked to emergency department and inpatient discharges for years 2005-2008. Medical outcomes were compared between partial and universal helmet law settings. We estimated adjusted relative …

Statistical Interpretation Including The Appropriate Statistical Tests, Olga A. Vsevolozhskaya

Biostatistics Presentations

Outline:

1. Evaluation of treatment’s therapeutic potential after experimental stroke.
2. Post-stroke behavioral testing and functional recovery.

Alzheimer's Biomarkers Are Correlated With Brain Connectivity In Older Adults Differentially During Resting And Task States, Yang Jiang, Haiqing Huang, Erin Abner, Lucas S. Broster, Gregory A. Jicha, Frederick A. Schmitt, Richard Kryscio, Anders H. Andersen, David Powell, Linda J. Van Eldik, Brian T. Gold, Peter T. Nelson, Charles D. Smith, Mingzhou Ding

Behavioral Science Faculty Publications

β-amyloid (Aβ) plaques and tau-related neurodegeneration are pathologic hallmarks of Alzheimer’s disease (AD). The utility of AD biomarkers, including those measured in cerebrospinal fluid (CSF), in predicting future AD risk and cognitive decline is still being refined. Here, we explored potential relationships between functional connectivity (FC) patterns within the default-mode network (DMN), age, CSF biomarkers (Aβ₄₂ and pTau₁₈₁), and cognitive status in older adults. Multiple measures of FC were explored, including a novel time series-based measure [total interdependence (TI)]. In our sample of 27 cognitively normal older adults, no significant associations were found between levels of Aβ …

Salvage Brachytherapy For Biochemically Recurrent Prostate Cancer Following Primary Brachytherapy, John M. Lacy, William A. Wilson, Raevti Bole, Li Chen, Ali S. Meigooni, Randall G. Rowland, William H. St. Clair

Urology Faculty Publications

Purpose. In this study, we evaluated our experience with salvage brachytherapy after discovery of biochemical recurrence after a prior brachytherapy procedure. Methods and Materials. From 2001 through 2012 twenty-one patients treated by brachytherapy within University of Kentucky or from outside centers developed biochemical failure and had no evidence of metastases. Computed tomography (CT) scans were evaluated; patients who had an underseeded portion of their prostate were considered for reimplantation. Results. The majority of the patients in this study (61.9%) were low risk and median presalvage PSA was 3.49 (range 17.41–1.68). Mean follow-up was 61 months. At last follow-up after reseeding, …

Statistical Methods For Environmental Exposure Data Subject To Detection Limits, Yuchen Yang

Theses and Dissertations--Statistics

In this dissertation, we develop unified and efficient nonparametric statistical methods for estimating and comparing environmental exposure distributions in presence of detection limits. In the first part, we propose a kernel-smoothed nonparametric estimator for the exposure distribution without imposing any independence assumption between the exposure level and detection limit. We show that the proposed estimator is consistent and asymptotically normal. Simulation studies demonstrate that the proposed estimator performs well in practical situations. A colon cancer study is provided for illustration. In the second part, we develop a class of test statistics to compare exposure distributions between two groups by using …

Improved Models For Differential Analysis For Genomic Data, Hong Wang

Theses and Dissertations--Statistics

This paper intend to develop novel statistical methods to improve genomic data analysis, especially for differential analysis. We considered two different data type: NanoString nCounter data and somatic mutation data. For NanoString nCounter data, we develop a novel differential expression detection method. The method considers a generalized linear model of the negative binomial family to characterize count data and allows for multi-factor design. Data normalization is incorporated in the model framework through data normalization parameters, which are estimated from control genes embedded in the nCounter system. For somatic mutation data, we develop beta-binomial model-based approaches to identify highly or lowly …

Evaluating A Bystander Intervention Program On Reproductive Coercion: Using Quasi-Experimental Design Strategies To Address Methodologic Issues In Randomized Community Prevention Trials, Catherine P. Starnes

Theses and Dissertations--Epidemiology and Biostatistics

Community (or cluster) randomized trials are trials in which communities or groups of individuals (clusters) are randomized to receive the intervention of interest. Community randomized trials frequently more closely resemble a natural experiment than a randomized controlled trial (RCT) following intervention allocation. In particular, the effects of non-compliance can pose methodologic challenges in estimating the intervention effect which may require a quasiexperimental approach in order to minimize bias.

The motivating example to illustrate these issues is the Green Dot High School (GDHS) study. The GDHS study was a longitudinal, cluster-randomized controlled trial designed to assess the effectiveness of a bystander …

Aggregated Quantitative Multifactor Dimensionality Reduction, Rebecca E. Crouch

Theses and Dissertations--Statistics

We consider the problem of making predictions for quantitative phenotypes based on gene-to-gene interactions among selected Single Nucleotide Polymorphisms (SNPs). Previously, Quantitative Multifactor Dimensionality Reduction (QMDR) has been applied to detect gene-to-gene interactions associated with elevated quantitative phenotypes, by creating a dichotomous predictor from one interaction which has been deemed optimal. We propose an Aggregated Quantitative Multifactor Dimensionality Reduction (AQMDR), which exhaustively considers all k-way interactions among a set of SNPs and replaces the dichotomous predictor from QMDR with a continuous aggregated score. We evaluate this new AQMDR method in a series of simulations for two-way and three-way interactions, …

Estimated Probability Of Becoming Alcohol Dependent: Extending A Multiparametric Approach, Olga A. Vsevolozhskaya, James C. Anthony

Biostatistics Presentations

Background: United States (US) epidemiological studies suggest that for every 5-8 who start drinking alcoholic beverages, at least one drinker will develop an alcohol dependence (AD) syndrome within the first 10 years after onset of drinking (Lopez-Quintero et al., 2011; Wagner & Anthony, 2002). Recently, we described a multiparametric functional analysis approach for new research to estimate these transition probabilities with a one-dimensional function (1D; Vsevolozhskaya & Anthony, 2015). Here, we demonstrate extension of this analysis to two-dimensional (2D) functions that combine information about number of recent drinking days and number of drinks on the typical drinking day.

Methods: Data …

Abcc9/Sur2 In The Brain: Implications For Hippocampal Sclerosis Of Aging And A Potential Therapeutic Target, Peter T. Nelson, Gregory A. Jicha, Wang-Xia Wang, Eseosa T. Ighodaro, Sergey C. Artiushin, Colin G. Nichols, David W. Fardo

Sanders-Brown Center on Aging Faculty Publications

The ABCC9 gene and its polypeptide product, SUR2, are increasingly implicated in human neurologic disease, including prevalent diseases of the aged brain. SUR2 proteins are a component of the ATP-sensitive potassium (“K _ATP ”) channel, a metabolic sensor for stress and/or hypoxia that has been shown to change in aging. The K _ATP channel also helps regulate the neurovascular unit. Most brain cell types express SUR2, including neurons, astrocytes, oligodendrocytes, microglia, vascular smooth muscle, pericytes, and endothelial cells. Thus it is not surprising that ABCC9 gene variants are associated with risk for human brain diseases. For example, Cantu syndrome is …

Functional Linear Models Extensions Uncover Pleiotropic Effects Of Chronic Pain Phenotypes, Dmitri V. Zaykin, L. Qing, G. D. Slade, R. Dubner, R. B. Fillingim, J. D. Greenspan, R. Ohrbach, W. Maixner, L. B. Diatchenko, Olga A. Vsevolozhskaya

Biostatistics Presentations

Growing scientific evidence suggests that intricate interactions of genetic risk factors with environmental exposures play a major role in the development of chronic pain conditions. In studies of relative contribution of an individual’s genetic composition to the perception of pain, the general characteristics of pain sensitivity are typically measured by a wide range of different, yet possibly etiologically related pain phenotypes. Testing each of these pain-perception traits individually is subject to problems of multiple testing and low statistical power. Furthermore, pain-related traits may share common etiology and comprise binary, categorical, and quantitative measurements. In the current study, we propose a …

Patient-Specific Variations In Biomarkers Across Gingivitis And Periodontitis, Radhakrishnan Nagarajan, Craig S. Miller, Dolph Dawson, Mohanad Al-Sabbagh, J. L. Ebersole

Biostatistics Faculty Publications

This study investigates the use of saliva, as an emerging diagnostic fluid in conjunction with classification techniques to discern biological heterogeneity in clinically labelled gingivitis and periodontitis subjects (80 subjects; 40/group) A battery of classification techniques were investigated as traditional single classifier systems as well as within a novel selective voting ensemble classification approach (SVA) framework. Unlike traditional single classifiers, SVA is shown to reveal patient-specific variations within disease groups, which may be important for identifying proclivity to disease progression or disease stability. Salivary expression profiles of IL-1ß, IL-6, MMP-8, and MIP-1α from 80 patients were analyzed using four classification …

Novel Human Abcc9/Sur2 Brain-Expressed Transcripts And An Eqtl Relevant To Hippocampal Sclerosis Of Aging, Peter T. Nelson, Wang-Xia Wang, Bernard R. Wilfred, Angela Wei, James Dimayuga, Qingwei Huang, Eseosa T. Ighodaro, Sergey C. Artiushin, David W. Fardo

Sanders-Brown Center on Aging Faculty Publications

ABCC9 genetic polymorphisms are associated with increased risk for various human diseases including hippocampal sclerosis of aging. The main goals of this study were 1 > to detect the ABCC9 variants and define the specific 3′ untranslated region (3′UTR) for each variant in human brain, and 2 > to determine whether a polymorphism (rs704180) associated with risk for hippocampal sclerosis of aging pathology is also associated with variation in ABCC9 transcript expression and/or splicing. Rapid amplification of ABCC9 cDNA ends (3′RACE) provided evidence of novel 3′ UTR portions of ABCC9 in human brain. In silico and experimental studies were performed focusing on …

Test On Existence Of Histology Subtype-Specific Prognostic Signatures Among Early Stage Lung Adenocarcinoma And Squamous Cell Carcinoma Patients Using A Cox-Model Based Filter, Suyan Tian, Chi Wang, Ming-Wen An

Biostatistics Faculty Publications

BACKGROUND: Non-small cell lung cancer (NSCLC) is the predominant histological type of lung cancer, accounting for up to 85% of cases. Disease stage is commonly used to determine adjuvant treatment eligibility of NSCLC patients, however, it is an imprecise predictor of the prognosis of an individual patient. Currently, many researchers resort to microarray technology for identifying relevant genetic prognostic markers, with particular attention on trimming or extending a Cox regression model. Adenocarcinoma (AC) and squamous cell carcinoma (SCC) are two major histology subtypes of NSCLC. It has been demonstrated that fundamental differences exist in their underlying mechanisms, which motivated us …

Impact Of Population Stratification On Family-Based Association In An Admixed Population, T. B. Mersha, L. Ding, H. He, E. S. Alexander, X. Zhang, B. G. Kurowski, V. Pilipenko, L. Kottyan, L. J. Martin, David W. Fardo

Biostatistics Faculty Publications

Population substructure is a well-known confounder in population-based case-control genetic studies, but its impact in family-based studies is unclear. We performed population substructure analysis using extended families of admixed population to evaluate power and Type I error in an association study framework. Our analysis shows that power was improved by 1.5% after principal components adjustment. Type I error was also reduced by 2.2% after adjusting for family substratification. The presence of population substructure was underscored by discriminant analysis, in which over 92% of individuals were correctly assigned to their actual family using only 100 principal components. This study demonstrates the …

Reassessment Of Risk Genotypes (Grn, Tmem106b, And Abcc9 Variants) Associated With Hippocampal Sclerosis Of Aging Pathology, Peter T. Nelson, Wang-Xia Wang, Amanda B. Partch, Sarah E. Monsell, Otto Valladares, Sally R. Ellingson, Bernard R. Wilfred, Adam C. Naj, Li-San Wang, Walter A. Kukull, David W. Fardo

Pathology and Laboratory Medicine Faculty Publications

Hippocampal sclerosis of aging (HS-Aging) is a common high-morbidity neurodegenerative condition in elderly persons. To understand the risk factors for HS-Aging, we analyzed data from the Alzheimer’s Disease Genetics Consortium and correlated the data with clinical and pathologic information from the National Alzheimer’s Coordinating Center database. Overall, 268 research volunteers with HS-Aging and 2,957 controls were included; detailed neuropathologic data were available for all. The study focused on single-nucleotide polymorphisms previously associated with HS-Aging risk: rs5848 ( GRN ), rs1990622 ( TMEM106B ), and rs704180 ( ABCC9 ). Analyses of a subsample that was not previously evaluated (51 HS-Aging cases …