Physical Sciences and Mathematics Commons^™

A Chromosome-Scale Genome Sequence Of Sudangrass (Sorghum Sudanense) Highlights The Genome Evolution And Regulation Of Dhurrin Biosynthesis, Paul W. Bible, Jieqin Li, Wenmiao Tu, Jian Zheng, Peng Jin, Yanlong Liu, Junli Du, Jiacheng Zheng, Yi-Hong Wang, Qiuwen Zhan

Computer Science Faculty publications

Sudangrass [ Sorghum sudanense (Piper) Stapf] is a hybrid between grain sorghum and its wild relative S. bicolor ssp. verticilliflorum and is grown as a forage crop due to its high biomass production and low dhurrin content compared to sorghum. In this study, we sequenced the sudangrass genome and showed that the assembled genome was 715.95 Mb with 35,243 protein-coding genes. Phylogenetic analysis with whole genome proteomes demonstrated that the sudangrass genome was more similar to US commercial sorghums than to its wild relatives and cultivated sorghums from Africa. We confirmed that at seedling stage, sudangrass accessions contained significantly lower …

Genomic Regions Associated With Pseudorabies Virus Infection Status In Naturally Infected Feral Swine (Sus Scrofa), Courtney F. Bowden, Jennifer N. Kiser, Ryan S. Miller, Alexandra C. Buckley, Paola M. Boggiatto, Rachael M. Giglio, Vienna R. Brown, Dorian Garrick, Holly L. Neibergs, Antoinette J. Piaggio, Scott E. Speidel, Timothy J. Smyser

USDA Wildlife Services: Staff Publications

Pseudorabies virus (PRV)—the causative agent of Aujeszky’s disease—was eliminated from commercial pig production herds in the United States (US) in 2004; however, PRV remains endemic among invasive feral swine (Sus scrofa). The circulation of PRV among abundant, widespread feral swine populations poses a sustained risk for disease spillover to production herds. Risk–based surveillance has been successfully implemented for PRV in feral swine populations in the US. However, understanding the role of host genetics in infection status may offer new insights into the epidemiology and disease dynamics of PRV that can be applied to management strategies. Genetic mechanisms underlying …

A Cross-Ancestry Genome-Wide Meta-Analysis, Fine-Mapping, And Gene Prioritization Approach To Characterize The Genetic Architecture Of Adiponectin, Casssandra N. Spracklen, Et. Al.

Biostatistics and Epidemiology Faculty Publications Series

No abstract provided.

An Autoencoder-Based Deep Learning Method For Genotype Imputation, Meng Song, Jonathan Greenbaum, Joseph Luttrell, Weihua Zhou, Chong Wu, Zhe Luo, Chuan Qiu, Lan Juan Zhao, Kuan Jui Su, Qing Tian, Hui Shen, Huixiao Hong, Ping Gong, Xinghua Shi, Hong Wen Deng, Chaoyang Zhang

Michigan Tech Publications

Genotype imputation has a wide range of applications in genome-wide association study (GWAS), including increasing the statistical power of association tests, discovering trait-associated loci in meta-analyses, and prioritizing causal variants with fine-mapping. In recent years, deep learning (DL) based methods, such as sparse convolutional denoising autoencoder (SCDA), have been developed for genotype imputation. However, it remains a challenging task to optimize the learning process in DL-based methods to achieve high imputation accuracy. To address this challenge, we have developed a convolutional autoencoder (AE) model for genotype imputation and implemented a customized training loop by modifying the training process with a …

An Autoencoder-Based Deep Learning Method For Genotype Imputation, Meng Song, Jonathan Greenbaum, Joseph Luttrell Iv, Weihua Zhou, Chong Wu, Zhe Luo, Chuan Qiu, Lan Juan Zhao, Kuan-Jui Su, Qing Tian, Hui Shen, Huixiao Hong, Ping Gong, Xinghua Shi, Hong-Wen Deng, Chaoyang Zhang

Faculty Publications

Genotype imputation has a wide range of applications in genome-wide association study (GWAS), including increasing the statistical power of association tests, discovering trait-associated loci in meta-analyses, and prioritizing causal variants with fine-mapping. In recent years, deep learning (DL) based methods, such as sparse convolutional denoising autoencoder (SCDA), have been developed for genotype imputation. However, it remains a challenging task to optimize the learning process in DL-based methods to achieve high imputation accuracy. To address this challenge, we have developed a convolutional autoencoder (AE) model for genotype imputation and implemented a customized training loop by modifying the training process with a …

Analysis Of Genetic Variants Associated With Levels Of Immune Modulating Proteins For Impact On Alzheimer’S Disease Risk Reveal A Potential Role For Siglec14, Benjamin C. Shaw, Yuriko Katsumata, James F. Simpson, David W. Fardo, Steven Estus

Biostatistics Faculty Publications

Genome-wide association studies (GWAS) have identified immune-related genes as risk factors for Alzheimer’s disease (AD), including TREM2 and CD33, frequently passing a stringent false-discovery rate. These genes either encode or signal through immunomodulatory tyrosine-phosphorylated inhibitory motifs (ITIMs) or activation motifs (ITAMs) and govern processes critical to AD pathology, such as inflammation and amyloid phagocytosis. To investigate whether additional ITIM and ITAM-containing family members may contribute to AD risk and be overlooked due to the stringent multiple testing in GWAS, we combined protein quantitative trait loci (pQTL) data from a recent plasma proteomics study with AD associations in a recent …

Combining Uav-Rgb High-Throughput Field Phenotyping And Genome-Wide Association Study To Reveal Genetic Variation Of Rice Germplasms In Dynamic Response To Drought Stress, Zhao Jiang, Haifu Tu, Baowei Bai, Chenghai Yang, Biquan Zhao, Ziyue Guo, Qian Liu, Hu Zhao, Wanneng Yang, Lizhong Xiong, Jian Zhang

School of Natural Resources: Faculty Publications

Accurate and high-throughput phenotyping of the dynamic response of a large rice population to drought stress in the field is a bottleneck for genetic dissection and breeding of drought resistance.

Here, high-efficiency and high-frequent image acquisition by an unmanned aerial vehicle (UAV) was utilized to quantify the dynamic drought response of a rice population under field conditions. Deep convolutional neural networks (DCNNs) and canopy height models were applied to extract highly correlated phenotypic traits including UAV-based leaf-rolling score (LRS_uav), plant water content (PWC_uav) and a new composite trait, drought resistance index by UAV (DRI_uav).

The DCNNs achieved high accuracy (correlation …

Statistical Methods In Genetic Studies, Cheng Gao

Dissertations, Master's Theses and Master's Reports

This dissertation includes three Chapters. A brief description of each chapter is organized as follows.

In Chapter 1, we proposed a new method, called MF-TOWmuT, for genome-wide association studies with multiple genetic variants and multiple phenotypes using family samples. MF-TOWmuT uses kinship matrix to account for sample relatedness. It is worth mentioning that in simulations, we considered hidden polygenic effects and varied the proportion of variance contributed by it to generate phenotypes. Simulation studies show that MF-TOWmuT can preserve the type I error rates and is more powerful than several existing methods in different simulation scenarios, MFTOWmuT is also quite …

Multi-Ancestry Genome-Wide Association Study Accounting For Gene-Psychosocial Factor Interactions Identifies Novel Loci For Blood Pressure Traits, Daokun Sun, Melissa A. Richard, Soloman K. Musani, Yun Ju Sung, Thomas W. Winkler, Karen Schwander, Jin Fang Chai, Xiuqing Guo, Tuomas O. Kilpeläinen, Dina Vojinovic, Hugues Aschard, Traci M. Bartz, Lawrence F. Bielak, Michael R. Brown, Kumaraswamy Chitrala, Fernando P. Hartwig, Andrea R. V. R. Horimoto, Yongmei Liu, Alisa K. Manning, Raymond Noordam, Donna K. Arnett

Epidemiology and Environmental Health Faculty Publications

Psychological and social factors are known to influence blood pressure (BP) and risk of hypertension and associated cardiovascular diseases. To identify novel BP loci, we carried out genome-wide association meta-analyses of systolic, diastolic, pulse, and mean arterial BP, taking into account the interaction effects of genetic variants with three psychosocial factors: depressive symptoms, anxiety symptoms, and social support. Analyses were performed using a two-stage design in a sample of up to 128,894 adults from five ancestry groups. In the combined meta-analyses of stages 1 and 2, we identified 59 loci (p value < 5e−8), including nine novel BP loci. The novel associations were observed mostly with pulse pressure, with fewer observed with mean arterial pressure. Five novel loci were identified in African ancestry, and all but one showed patterns of interaction with at least one psychosocial factor. Functional annotation of the novel loci supports a major role for genes implicated in the immune response (PLCL2), synaptic function and neurotransmission (LIN7A …

A New Efficient Method To Detect Genetic Interactions For Lung Cancer Gwas, Jennifer Luyapan, Xuemei Ji, Siting Li, Xiangjun Xiao, Dakai Zhu, Eric J. Duell, David C. Christiani, Matthew B. Schabath, Susanne M. Arnold, Shanbeh Zienolddiny, Hans Brunnström, Olle Melander, Mark D. Thornquist, Todd A. Mackenzie, Christopher I. Amos, Jiang Gui

Markey Cancer Center Faculty Publications

BACKGROUND: Genome-wide association studies (GWAS) have proven successful in predicting genetic risk of disease using single-locus models; however, identifying single nucleotide polymorphism (SNP) interactions at the genome-wide scale is limited due to computational and statistical challenges. We addressed the computational burden encountered when detecting SNP interactions for survival analysis, such as age of disease-onset. To confront this problem, we developed a novel algorithm, called the Efficient Survival Multifactor Dimensionality Reduction (ES-MDR) method, which used Martingale Residuals as the outcome parameter to estimate survival outcomes, and implemented the Quantitative Multifactor Dimensionality Reduction method to identify significant interactions associated with age of …

Loci Associated With Antibody Response In Feral Swine (Sus Scrofa) Infected With Brucella Suis, Courtney F. Pierce, Vienna R. Brown, Steven C. Olsen, Paola Boggiatto, Kerri Pedersen, Ryan S. Miller, Scott E. Speidel, Timothy J. Smyser

USDA Wildlife Services: Staff Publications

Feral swine (Sus scrofa) are a destructive invasive species widespread throughout the United States that disrupt ecosystems, damage crops, and carry pathogens of concern for the health of domestic stock and humans including Brucella suis—the causative organism for swine brucellosis. In domestic swine, brucellosis results in reproductive failure due to abortions and infertility. Contact with infected feral swine poses spillover risks to domestic pigs as well as humans, companion animals, wildlife, and other livestock. Genetic factors influence the outcome of infectious diseases; therefore, genome wide association studies (GWAS) of differential immune responses among feral swine can provide …

Genome-Wide Association Study In Accessions Of The Mini-Core Collection Of Mungbean (Vigna Radiata) From The World Vegetable Gene Bank (Taiwan), Alena Sokolkova, Marina Burlyaeva, Tatjana Valiannikova, Margarita Vishnyakova, Roland Schafleitner, Cheng Ruei Lee, Chau Ti Ting, Ramakrishnan Madhavan Nair, Sergey Nuzhdin, Maria Samsonova, Eric Von Wettberg

College of Agriculture and Life Sciences Faculty Publications

Background: Mungbean (Vigna radiata (L.) R. Wilczek, or green gram) is important tropical and sub-tropical legume and a rich source of dietary protein and micronutrients. In this study we employ GWAS to examine the genetic basis of variation in several important traits in mungbean, using the mini-core collection established by the World Vegetable Center, which includes 296 accessions that represent the major market classes. This collection has been grown in a common field plot in southern European part of Russia in 2018. Results: We used 5041 SNPs in 293 accessions that passed strict filtering for genetic diversity, linkage disequilibrium, population …

Dynamical Climatic Model For Time To Flowering In Vigna Radiata, Konstantin Kozlov, Alena Sokolkova, Cheng Ruei Lee, Chau Ti Ting, Roland Schafleitner, Eric Bishop-Von Wettberg, Sergey Nuzhdin, Maria Samsonova

College of Agriculture and Life Sciences Faculty Publications

Background: Phenology data collected recently for about 300 accessions of Vigna radiata (mungbean) is an invaluable resource for investigation of impacts of climatic factors on plant development. Results: We developed a new mathematical model that describes the dynamic control of time to flowering by daily values of maximal and minimal temperature, precipitation, day length and solar radiation. We obtained model parameters by adaptation to the available experimental data. The models were validated by cross-validation and used to demonstrate that the phenology of adaptive traits, like flowering time, is strongly predicted not only by local environmental factors but also by plant …

Association Of Copy Number Variations With Chronic Hepatitis B In Chinese Population, Fang Niu

Capstone Experience

With one third of the Hepatitis B virus (HBV) infection population of the world, chronic Hepatitis B (CHB) has become a top burden in China. CHB is a lifelong infection with HBV which can cause serious health problems, like cirrhosis, liver cancer or even death. HBV infection is known to result in various clinical conditions, including asymptomatic HBV carriers to chronic hepatitis and primary hepatocellular carcinoma. Several studies have shown that host genetic susceptibility could be an important factor that determines these various outcomes of HBV infection. Many Single Nucleotide Polymorphisms (SNPs) and Copy Number Variations (CNVs) have been associated …

Substantial Contribution Of Genetic Variation In The Expression Of Transcription Factors To Phenotypic Variation Revealed By Erd-Gwas, Hung-Ying Lin, Qiang Liu, Xiao Li, Jinliang Yang, Sanzhen Liu, Yinlian Huang, Michael J. Scanlon, Dan Nettleton, Patrick S. Schnable

Dan Nettleton

Background: There are significant limitations in existing methods for the genome-wide identification of genes whose expression patterns affect traits.

Results: The transcriptomes of five tissues from 27 genetically diverse maize inbred lines were deeply sequenced to identify genes exhibiting high and low levels of expression variation across tissues or genotypes. Transcription factors are enriched among genes with the most variation in expression across tissues, as well as among genes with higher-than-median levels of variation in expression across genotypes. In contrast, transcription factors are depleted among genes whose expression is either highly stable or highly variable across genotypes. We developed a …

Non-Linear Regression Models For Time To Flowering In Wild Chickpea Combine Genetic And Climatic Factors, Konstantin Kozlov, Anupam Singh, Jens Berger, Eric Bishop-Von Wettberg, Abdullah Kahraman, Abdulkadir Aydogan, Douglas Cook, Sergey Nuzhdin, Maria Samsonova

College of Agriculture and Life Sciences Faculty Publications

Background: Accurate prediction of crop flowering time is required for reaching maximal farm efficiency. Several models developed to accomplish this goal are based on deep knowledge of plant phenology, requiring large investment for every individual crop or new variety. Mathematical modeling can be used to make better use of more shallow data and to extract information from it with higher efficiency. Cultivars of chickpea, Cicer arietanum, are currently being improved by introgressing wild C. reticulatum biodiversity with very different flowering time requirements. More understanding is required for how flowering time will depend on environmental conditions in these cultivars developed by …

Phenogeneranker: A Tool For Gene Prioritization Using Complete Multiplex Heterogeneous Networks, Cagatay Dursun, Naoki Shimoyama, Mary Shimoyama, Michael Schläppi, Serdar Bozdag

Computer Science Faculty Research and Publications

Uncovering genotype-phenotype relationships is a fundamental challenge in genomics. Gene prioritization is an important step for this endeavor to make a short manageable list from a list of thousands of genes coming from high-throughput studies. Network propagation methods are promising and state of the art methods for gene prioritization based on the premise that functionally-related genes tend to be close to each other in the biological networks.

In this study, we present PhenoGeneRanker, an improved version of a recently developed network propagation method called Random Walk with Restart on Multiplex Heterogeneous Networks (RWR-MH). PhenoGeneRanker allows multi-layer gene and disease networks. …

Gwas For Fusarium Head Blight Related Traits In Winter Wheat (Triticum Aestivum L.) In An Artificially Warmed Treatment, Elisane W. Tessmann, David A. Van Sanford

Plant and Soil Sciences Faculty Publications

Global temperature increases will affect Fusarium head blight (FHB) levels in wheat (Triticum aestivum L.). A pressing question is whether current sources of resistance will be effective in a warmer environment. We evaluated phenotypic response to disease in 238 soft winter wheat breeding lines and cultivars grown in 2015–2016 and 2016–2017 under control and warmed (+3 °C) conditions. Warming was achieved with heating cables buried 3 cm in the rhizosphere. We measured heading date, plant height, yield, FHB rating, Fusarium damaged kernels (FDK), deoxynivalenol (DON), leaf blotch rating, powdery mildew rating and leaf rust rating. There were significant ( …

Bayesian Network Modeling And Inference Of Gwas Catalog, Qiuping Pan

Graduate Theses and Dissertations

Genome-wide association studies (GWASs) have received an increasing attention to understand genotype-phenotype relationships. The Bayesian network has been proposed as a powerful tool for modeling single-nucleotide polymorphism (SNP)-trait associations due to its advantage in addressing the high computational complex and high dimensional problems. Most current works learn the interactions among genotypes and phenotypes from the raw genotype data. However, due to the privacy issue, genotype information is sensitive and should be handled by complying with specific restrictions. In this work, we aim to build Bayesian networks from publicly released GWAS statistics to explicitly reveal the conditional dependency between SNPs and …

Genome-Wide Association Analysis With A 50k Transcribed Gene Snp-Chip Identifies Qtl Affecting Muscle Yield In Rainbow Trout, Mohamed Salem, Rafet Al-Tobasei, Ali Ali, Daniela Lourenco, Guangtu Gao, Yniv Palti, Brett Kenney, Timothy D. Leeds

Faculty & Staff Scholarship

Detection of coding/functional SNPs that change the biological function of a gene may lead to identification of putative causative alleles within QTL regions and discovery of genetic markers with large effects on phenotypes. This study has two-fold objectives, first to develop, and validate a 50K transcribed gene SNP-chip using RNA-Seq data. To achieve this objective, two bioinformatics pipelines, GATK and SAMtools, were used to identify ∼21K transcribed SNPs with allelic imbalances associated with important aquaculture production traits including body weight, muscle yield, muscle fat content, shear force, and whiteness in addition to resistance/susceptibility to bacterial cold-water disease (BCWD). SNPs ere …

Joint Analysis For Multiple Traits, Zhenchuan Wang

Dissertations, Master's Theses and Master's Reports

This dissertation includes three papers with each distributed in one chapter.

In chapter 1, we proposed an Adaptive Weighting Reverse Regression (AWRR) method to test association between multiple traits and rare variants in a genomic region. AWRR is robust to the directions of effects of causal variants and is also robust to the directions of association of traits. Using extensive simulation studies, we compared the performance of AWRR with canonical correlation analysis (CCA), Single-TOW, and the Weighted Sum Reverse Regression (WSRR). Our results showed that, in all of the simulation scenarios, AWRR is consistently more powerful than CCA. In most …

Penalized Mixed-Effects Ordinal Response Models For High-Dimensional Genomic Data In Twins And Families, Amanda E. Gentry

Theses and Dissertations

The Brisbane Longitudinal Twin Study (BLTS) was being conducted in Australia and was funded by the US National Institute on Drug Abuse (NIDA). Adolescent twins were sampled as a part of this study and surveyed about their substance use as part of the Pathways to Cannabis Use, Abuse and Dependence project. The methods developed in this dissertation were designed for the purpose of analyzing a subset of the Pathways data that includes demographics, cannabis use metrics, personality measures, and imputed genotypes (SNPs) for 493 complete twin pairs (986 subjects.) The primary goal was to determine what combination of SNPs and …

Genomic And Physiological Approaches To Improve Drought Tolerance In Soybean, Avjinder Kaler

Graduate Theses and Dissertations

Drought stress is a major global constraint for crop production, and improving crop tolerance to drought is of critical importance. Direct selection of drought tolerance among genotypes for yield is limited because of low heritability, polygenic control, epistasis effects, and genotype by environment interactions. Crop physiology can play a major role for improving drought tolerance through the identification of traits associated with drought tolerance that can be used as indirect selection criteria in a breeding program. Carbon isotope ratio (δ13C, associated with water use efficiency), oxygen isotope ratio (δ18O, associated with transpiration), canopy temperature (CT), canopy wilting, and canopy coverage …

Methods To Account For Breed Composition In A Bayesian Gwas Method Which Utilizes Haplotype Clusters, Danielle F. Wilson-Wells

Department of Statistics: Dissertations, Theses, and Student Work

In livestock, prediction of an animal’s genetic merit using genomic information is becoming increasingly common. The models used to make these predictions typically assume that we are sampling from a homogeneous population. However, in both commercial and experimental populations the sire and dam of an individual may be a mixture of different breeds. Haplotype models can capture this population structure.

Two models based on breed specific haplotype clusters where developed to account for differences across multiple breeds. The first model utilizes the breed composition of the individual, while the second utilizes the breed composition from the sire and dam. Haplotype …

A Bayesian Gwas Method Utilizing Haplotype Clusters For A Composite Breed Population, Danielle F. Wilson-Wells, Stephen D. Kachman

Conference on Applied Statistics in Agriculture

Commercial beef cattle are often composites of multiple breeds. Current methods used to produce genomic predictors are based on the underlying assumption of animals being sampled from a homogeneous population. As a result, the predictors can perform poorly when used to predict the relative genetic merit of animals whose breed composition are different. In part, this is due to the changes in linkage disequilibrium between the markers and the quantitative trait loci as we move from one breed to the next. An alternative model based on breed specific haplotype clusters was developed to allow for differences in linkage disequilibrium across …

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 …

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 …

Genetic Predictors Of Metabolic Side Effects Of Diuretic Therapy, Jorge L. Del Aguila

Dissertations & Theses (Open Access)

Thiazide diuretics are a recommended first-line monotherapy for hypertension (i.e.SBP>140 mmHg or DBP>90 mmHg). Even so, diuretics are associated with adverse metabolic side effects, such as hyperlipidemia, hyperglycemia and hypokalemia which increase the risk of developing type II diabetes. This thesis used three analytical strategies to identify and quantify genetic factors that contribute to the development of adverse metabolic effects due to thiazide diuretic treatment. I performed a genome-wide association study (GWAS) and meta-analysis of the change in fasting plasma glucose and triglycerides in response to HCTZ from two different clinical trials: the Pharmacogenomic Evaluation of Antihypertensive Responses …

Sberia: Set Based Gene Environment Interaction Test For Rare And Common Variants In Complex Diseases, Shuo Jiao, Li Hsu, Stéphane Bézieau, Hermann Brenner, Andrew T. Chan, Jenny Chang-Claude, Loic Le Marchand, Mathieu Lemire, Polly A. Newcomb, Martha L. Slattery, Ulrike Peters

Shuo Jiao

Identification of gene-environment interaction (GxE) is important in understanding the etiology of complex diseases. However, partially due to the lack of power, there have been very few replicated GxE findings compared to the success in marginal association studies. The existing GxE testing methods mainly focus on improving the power for individual markers. In this paper, we took a different strategy and proposed a Set Based gene EnviRonment InterAction test (SBERIA), which can improve the power by reducing the multiple testing burdens and aggregating signals within a set. The major challenge of the signal aggregation within a set is how to …

Gene By Bmi Interactions Influencing C-Reactive Protein Levels In European-Americans, Sarah Tudor

Dissertations & Theses (Open Access)

C-Reactive Protein (CRP) is a biomarker indicating tissue damage, inflammation, and infection. High-sensitivity CRP (hsCRP) is an emerging biomarker often used to estimate an individual’s risk for future coronary heart disease (CHD). hsCRP levels falling below 1.00 mg/l indicate a low risk for developing CHD, levels ranging between 1.00 mg/l and 3.00 mg/l indicate an elevated risk, and levels exceeding 3.00 mg/l indicate high risk. Multiple Genome-Wide Association Studies (GWAS) have identified a number of genetic polymorphisms which influence CRP levels. SNPs implicated in such studies have been found in or near genes of interest including: CRP, APOE, APOC, IL-6, …