You searched for +publisher:"Vanderbilt University" +contributor:("Bingshan Li").
Showing records 1 – 11 of
11 total matches.
No search limiters apply to these results.
Vanderbilt University
1.
Han, Mi-Ryung.
Rare coding variants in GWAS identified loci with breast cancer risk.
Degree: PhD, Epidemiology, 2016, Vanderbilt University
URL: http://hdl.handle.net/1803/10872 
► To date, common genetic variants in ~ 109 loci have been identified for breast cancer risk via genome-wide association studies (GWAS). Most common variants found…
(more)
▼ To date, common genetic variants in ~ 109 loci have been identified for breast cancer risk via genome-wide association studies (GWAS). Most common variants found in GWAS are located in non-coding region, thus impeding the direct interpretation of their functional effects. They may be involved in regulation of gene expression, and rare functional variants in the coding region of these genes may change gene structure and function. These rare coding variants may contribute to breast cancer risk.
Candidate genes were identified through systematic analysis of expression quantitative trait loci (eQTL) using three major sources; the Cancer Genome Atlas (TCGA), the Genotype-Tissue Expression (GTEx), and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC). We prioritized functional variants into two groups, nonsynonymous and loss-of-function (LOF), using functional prediction algorithm. A total of 9,004 cases and 11,996 controls from three ethnic groups including Chinese, European Americans, and African Americans were investigated to examine associations of rare coding variants with breast cancer risk. Our comprehensive association analysis including additive and recessive models revealed potential candidate genes and rare coding variants associated with breast cancer risk.
Advisors/Committee Members: Todd L. Edwards (committee member), Wei Zheng (committee member), Bingshan Li (committee member), Jirong Long (Committee Chair).
Subjects/Keywords: GWAS; Rare coding variant; Breast cancer
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Han, M. (2016). Rare coding variants in GWAS identified loci with breast cancer risk. (Doctoral Dissertation). Vanderbilt University. Retrieved from http://hdl.handle.net/1803/10872
Chicago Manual of Style (16th Edition):
Han, Mi-Ryung. “Rare coding variants in GWAS identified loci with breast cancer risk.” 2016. Doctoral Dissertation, Vanderbilt University. Accessed March 07, 2021.
http://hdl.handle.net/1803/10872.
MLA Handbook (7th Edition):
Han, Mi-Ryung. “Rare coding variants in GWAS identified loci with breast cancer risk.” 2016. Web. 07 Mar 2021.
Vancouver:
Han M. Rare coding variants in GWAS identified loci with breast cancer risk. [Internet] [Doctoral dissertation]. Vanderbilt University; 2016. [cited 2021 Mar 07].
Available from: http://hdl.handle.net/1803/10872.
Council of Science Editors:
Han M. Rare coding variants in GWAS identified loci with breast cancer risk. [Doctoral Dissertation]. Vanderbilt University; 2016. Available from: http://hdl.handle.net/1803/10872
Vanderbilt University
2.
D'Aoust, Laura Nicole.
Examination of Candidate Exonic Variants that Confer Susceptibility to Alzheimer Disease in the Amish.
Degree: PhD, Human Genetics, 2015, Vanderbilt University
URL: http://hdl.handle.net/1803/10861
► Alzheimer disease (AD) is the most common cause of dementia. As with many complex diseases, the identified variants do not explain the total expected genetic…
(more)
▼ Alzheimer disease (AD) is the most common cause of dementia. As with many complex diseases, the identified variants do not explain the total expected genetic risk that is based on heritability estimates for AD. Isolated founder populations, such as the Amish, are advantageous for genetic studies as they overcome limitations associated with complex population studies. Amish AD cases harbored a significantly higher burden of the known risk alleles compared to Amish cognitively normal controls, but a significantly lower burden when compared to cases from a cohort of unrelated individuals. These results suggest that known loci explain some of the genetic effects and that there may be different underlying genetic architectures between the two populations. Whole-exome sequencing of a selected subset of the overall study population was used as a screening tool to identify variants located in the regions of the genome that are most likely to contribute risk. By then genotyping the top candidate variants from the known AD genes and implicated linkage regions from previous studies in the full data set, new associations could be confirmed. The most significant result (p = 0.0012) was for rs73938538, a synonymous variant in LAMA1 within the previously identified linkage peak on chromosome 18, but this association did not generalize when tested in a dataset of unrelated individuals. These results indicate that exonic variation in a majority of previously associated LOAD genes, and regions implicated by previous linkage studies, does not contribute to risk for LOAD in the Amish.
Advisors/Committee Members: Paul Newhouse (committee member), Tricia Thornton-Wells (committee member), Jonathan L Haines (committee member), Bingshan Li (committee member), Dana Crawford (Committee Chair).
Subjects/Keywords: Alzheimer; family-based study; genetics
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
D'Aoust, L. N. (2015). Examination of Candidate Exonic Variants that Confer Susceptibility to Alzheimer Disease in the Amish. (Doctoral Dissertation). Vanderbilt University. Retrieved from http://hdl.handle.net/1803/10861
Chicago Manual of Style (16th Edition):
D'Aoust, Laura Nicole. “Examination of Candidate Exonic Variants that Confer Susceptibility to Alzheimer Disease in the Amish.” 2015. Doctoral Dissertation, Vanderbilt University. Accessed March 07, 2021.
http://hdl.handle.net/1803/10861.
MLA Handbook (7th Edition):
D'Aoust, Laura Nicole. “Examination of Candidate Exonic Variants that Confer Susceptibility to Alzheimer Disease in the Amish.” 2015. Web. 07 Mar 2021.
Vancouver:
D'Aoust LN. Examination of Candidate Exonic Variants that Confer Susceptibility to Alzheimer Disease in the Amish. [Internet] [Doctoral dissertation]. Vanderbilt University; 2015. [cited 2021 Mar 07].
Available from: http://hdl.handle.net/1803/10861.
Council of Science Editors:
D'Aoust LN. Examination of Candidate Exonic Variants that Confer Susceptibility to Alzheimer Disease in the Amish. [Doctoral Dissertation]. Vanderbilt University; 2015. Available from: http://hdl.handle.net/1803/10861
Vanderbilt University
3.
Moore, Carrie Colleen Buchanan.
A biologically informed method for detecting associations with rare variants.
Degree: PhD, Human Genetics, 2013, Vanderbilt University
URL: http://hdl.handle.net/1803/14835
► Many recent studies have identified rare variants that contribute to common, complex disease. It is believed that rare variants likely have a larger effect size…
(more)
▼ Many recent studies have identified rare variants that contribute to common, complex disease. It is believed that rare variants likely have a larger effect size (compared to GWAS findings) and can act alone, in concert with other rare variants, or together with common variants. Multiple rare variants can potentially account for a portion of missing heritability in a given trait; therefore, binning or burden testing, may better account for genetic heterogeneity. BioBin, an innovative collapsing method developed in the Ritchie lab, utilizes a flexible repository of data assembled from multiple public databases.
The novelty of BioBin lies in access to comprehensive knowledge-guided multi-level binning. BioBin can apply multiple levels of burden testing, including: functional regions, evolutionary conserved regions, genes, and/or pathways. BioBin does not include a specific statistical association test, since the application of statistical testing is dependent on data type and analysis in question. Therefore, the user has the flexibility to apply tests appropriately without constraint.
BioBin has been tested in the context of extensive simulation studies, compared with multiple published statistical methods, and applied to the NHLBI GO Exome Sequencing Project for Cystic Fibrosis. BioBin is a very useful and flexible tool to analyze sequence data and can uncover novel associations with complex disease.
Advisors/Committee Members: Tricia Thornton-Wells (committee member), Dan Roden (committee member), William Bush (committee member), Marylyn Ritchie (committee member), Bingshan Li (Committee Chair).
Subjects/Keywords: collapsing methods; 1000 Genomes Project data; next-generation sequencing; genomics; rare variants
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Moore, C. C. B. (2013). A biologically informed method for detecting associations with rare variants. (Doctoral Dissertation). Vanderbilt University. Retrieved from http://hdl.handle.net/1803/14835
Chicago Manual of Style (16th Edition):
Moore, Carrie Colleen Buchanan. “A biologically informed method for detecting associations with rare variants.” 2013. Doctoral Dissertation, Vanderbilt University. Accessed March 07, 2021.
http://hdl.handle.net/1803/14835.
MLA Handbook (7th Edition):
Moore, Carrie Colleen Buchanan. “A biologically informed method for detecting associations with rare variants.” 2013. Web. 07 Mar 2021.
Vancouver:
Moore CCB. A biologically informed method for detecting associations with rare variants. [Internet] [Doctoral dissertation]. Vanderbilt University; 2013. [cited 2021 Mar 07].
Available from: http://hdl.handle.net/1803/14835.
Council of Science Editors:
Moore CCB. A biologically informed method for detecting associations with rare variants. [Doctoral Dissertation]. Vanderbilt University; 2013. Available from: http://hdl.handle.net/1803/14835
Vanderbilt University
4.
Zeng, Chenjie.
Genetic markers of 5-fluorouracil associated-toxicity in
colorectal cancer patients.
Degree: PhD, Epidemiology, 2017, Vanderbilt University
URL: http://hdl.handle.net/1803/15548
► Previous pharmacogenetics studies of 5-fluorouracil (5-FU) have focused on coding variants, and only four of these variants showed consistent association, which explained a small fraction…
(more)
▼ Previous pharmacogenetics studies of 5-fluorouracil (5-FU) have focused on coding variants, and only four of these variants showed consistent association, which explained a small fraction of the heritability of 5-FU-associated toxicity. No previous studies have systematically investigated non-coding variants that regulate expression of 5-FU catabolic genes and their roles in 5-FU-associated toxicity in cancer patients. This dissertation developed approaches that integrated multiple functional genomics datasets to identify variants predicting expression of genes in normal tissues and prioritize additional potential regulatory variants for 5-FU catabolic genes including DPYD, DPYS and UPB1. To investigate the role of these genetic variants, a cohort of 424 colorectal cancer patients was established using resources from the
Vanderbilt cancer registry and the biobank, BioVU. It was found that a decrease in the genetically predicted expression of catabolic genes was associated with an increased risk of severe toxicity (OR per one standard deviation decrease = 1.28, 95% CI: 1.05-1.59, P = 0.02), and the genetic risk score combining all prioritized potential regulatory variants were positively associated with the risk of severe toxicity (OR per effect allele = 1.33, 95% CI: 1.09-1.61, P = 0.004). In combination with known genetic and non-genetic risk factors, these genetic markers together provided moderate discriminatory accuracy for predicting severe toxicity. This dissertation has supported the important role of regulatory variants in the risk of 5-FU associated toxicity, identified a panel of markers of potential clinical use and provided a new direction for future pharmacogenetics studies.
Advisors/Committee Members: Bingshan Li (committee member), Chang Yu (committee member), Todd L. Edwards (committee member), Wei Zheng (Committee Chair).
Subjects/Keywords: pharmacogenetics; genetics; 5-FU; toxicity; side effects; colorectal cancer
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Zeng, C. (2017). Genetic markers of 5-fluorouracil associated-toxicity in
colorectal cancer patients. (Doctoral Dissertation). Vanderbilt University. Retrieved from http://hdl.handle.net/1803/15548
Chicago Manual of Style (16th Edition):
Zeng, Chenjie. “Genetic markers of 5-fluorouracil associated-toxicity in
colorectal cancer patients.” 2017. Doctoral Dissertation, Vanderbilt University. Accessed March 07, 2021.
http://hdl.handle.net/1803/15548.
MLA Handbook (7th Edition):
Zeng, Chenjie. “Genetic markers of 5-fluorouracil associated-toxicity in
colorectal cancer patients.” 2017. Web. 07 Mar 2021.
Vancouver:
Zeng C. Genetic markers of 5-fluorouracil associated-toxicity in
colorectal cancer patients. [Internet] [Doctoral dissertation]. Vanderbilt University; 2017. [cited 2021 Mar 07].
Available from: http://hdl.handle.net/1803/15548.
Council of Science Editors:
Zeng C. Genetic markers of 5-fluorouracil associated-toxicity in
colorectal cancer patients. [Doctoral Dissertation]. Vanderbilt University; 2017. Available from: http://hdl.handle.net/1803/15548
Vanderbilt University
5.
Giri, Ayush.
Modifiable and non-modifiable risk factors for pelvic organ prolapse.
Degree: PhD, Epidemiology, 2015, Vanderbilt University
URL: http://hdl.handle.net/1803/14413
► Pelvic organ prolapse (POP) is characterized by the descent of pelvic organs (uterus, bladder, and bowels) from their normal anatomical positions into the vaginal space…
(more)
▼ Pelvic organ prolapse (POP) is characterized by the descent of pelvic organs (uterus, bladder, and bowels) from their normal anatomical positions into the vaginal space due to defects in the pelvic floor support system. Obesity may influence POP but findings from studies are not always consistent. A systematic-review of the literature was undertaken here and a meta-analysis was conducted to evidence that being over-weight and obese increased odds of having POP, compared with women with normal-weight. Literature suggests POP is heritable, and is likely influenced by a host of predisposing and modifiable factors; however this notion of interaction has not been formally assessed. Considering childbirth is the strongest risk factor and obesity, the most-practicably modifiable risk factor for POP, analyses were undertaken to identify whether single nucleotide polymorphisms (SNPs) in/around 96 candidate genes modify the associations between parity and POP and body mass index (BMI) and POP in European American, African American and Hispanic women from the Women’s Health Initiative Hormone Therapy (WHI-HT) trial. Although signals were not statistically significant considering multiple-comparisons, SNPs from several potential gene regions were noted to interact with BMI (<i>COL11A1</i>, <i>CADM2</i>, <i>ELN</i>, <i>ACTN3</i>, <i>NRXN3</i>, <i>FTO</i>, and <i>TMEM160</i>) and with parity (<i>CADM2</i>, <i>ETV5</i>, and <i>ITPR2</i>) to influence POP. Epidemiologic evidence also suggests racial disparity in POP prevalence; however, whether continental genetic ancestry plays a part has not been examined. An admixture mapping study of POP was undertaken in African American women from the WHI-HT. One chromosomal region (15:q262) showed a statistically significant inverse association with European ancestry, while another (1:q42.1-42.3) showed a suggestive positive association with European ancestry in relation to POP. This work demonstrates the multifactorial etiology of POP and the need to further investigate the mechanisms of how these factors interrelate to manifest POP.
Advisors/Committee Members: Katherine E. Hartmann (committee member), Digna R. Velez Edwards (committee member), Melinda C. Aldrich (committee member), Bingshan Li (committee member), Todd L. Edwards (Committee Chair).
Subjects/Keywords: Epidemiology of POP; Admixture mapping; Gene-environment interactions; Obesity and pelvic organ prolapse; Pelvic organ prolapse (POP); Women's Health
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Giri, A. (2015). Modifiable and non-modifiable risk factors for pelvic organ prolapse. (Doctoral Dissertation). Vanderbilt University. Retrieved from http://hdl.handle.net/1803/14413
Chicago Manual of Style (16th Edition):
Giri, Ayush. “Modifiable and non-modifiable risk factors for pelvic organ prolapse.” 2015. Doctoral Dissertation, Vanderbilt University. Accessed March 07, 2021.
http://hdl.handle.net/1803/14413.
MLA Handbook (7th Edition):
Giri, Ayush. “Modifiable and non-modifiable risk factors for pelvic organ prolapse.” 2015. Web. 07 Mar 2021.
Vancouver:
Giri A. Modifiable and non-modifiable risk factors for pelvic organ prolapse. [Internet] [Doctoral dissertation]. Vanderbilt University; 2015. [cited 2021 Mar 07].
Available from: http://hdl.handle.net/1803/14413.
Council of Science Editors:
Giri A. Modifiable and non-modifiable risk factors for pelvic organ prolapse. [Doctoral Dissertation]. Vanderbilt University; 2015. Available from: http://hdl.handle.net/1803/14413
Vanderbilt University
6.
Sobota, Rafal Sebastian.
Genetics of Tuberculosis Resistance.
Degree: PhD, Human Genetics, 2015, Vanderbilt University
URL: http://hdl.handle.net/1803/12103
► One third of the world’s population has been infected with Mycobacterium tuberculosis (MTB). Most of those exposed develop an asymptomatic latent infection. In the absence…
(more)
▼ One third of the world’s population has been infected with Mycobacterium tuberculosis (MTB). Most of those exposed develop an asymptomatic latent infection. In the absence of co-morbidities, only 5-10% of people progress to active tuberculosis disease (TB) post-exposure, defined as primary TB. However, immunosuppression resulting from malnutrition or human immunodeficiency virus (HIV) co-infection increases the likelihood of both primary TB and activation of a latent infection. As a result, tuberculosis remains a major global health problem. Worldwide, TB is the second-leading cause of mortality from a single infectious agent, after HIV. In 2013, 9 million new cases of clinical tuberculosis were diagnosed and 1.5 million deaths were attributed to the disease. An estimated 360,000 deaths occurred in people co-infected with HIV, and 75% of these cases occurred in sub-Saharan Africa.
MTB infection and tuberculosis disease have a substantial heritable component. In this project, we studied a genetic resistance phenotype to TB disease and MTB infection, as opposed to more standard approaches tailored towards finding loci associated with susceptibility. We recruited HIV-positive patients from three recently concluded prospective cohorts of TB from Uganda and Tanzania. We hypothesized that HIV-positive individuals living in MTB hyperendemic areas who do not develop TB disease represent an extreme resistance phenotype. A study of 175,906 variants in 267 cases and 314 controls revealed a genome-wide significant association of a common TB resistance single nucleotide polymorphism, rs4921437, in the regulatory region of IL12, a gene previously associated with susceptibility. We also hypothesized that HIV-positive individuals who do not establish MTB infection despite living in hyperendemic regions are genetically resistant. In a study of 162,228 variants in 244 cases and 235 controls, we discovered a genome-wide significant association of a resistance variant rs877356 near IL9, a gene previously associated with bronchial hyperresponsiveness and asthma. Furthermore, we evaluated the effects of multi-locus interactions in a candidate gene approach and found that epistasis also plays a significant role in risk of MTB infection and TB disease.
We present a novel approach to genome-wide association studies, also applicable to whole genome sequencing studies, where the use of an extreme resistance phenotype allowed us to identify large effect sizes and attain genome-wide significance in cohorts of a relatively small sample size. The use of HIV status as a central feature of our hypothesis as opposed to a confounder or exclusion criterion is also unique.
Advisors/Committee Members: Scott M. Williams (committee member), Jonathan L. Haines (committee member), Luc Van Kaer (committee member), Carl H. Johnson (committee member), Dana C. Crawford (Committee Chair), Bingshan Li (Committee Chair).
Subjects/Keywords: il9; tuberculosis; il12b; gwas
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Sobota, R. S. (2015). Genetics of Tuberculosis Resistance. (Doctoral Dissertation). Vanderbilt University. Retrieved from http://hdl.handle.net/1803/12103
Chicago Manual of Style (16th Edition):
Sobota, Rafal Sebastian. “Genetics of Tuberculosis Resistance.” 2015. Doctoral Dissertation, Vanderbilt University. Accessed March 07, 2021.
http://hdl.handle.net/1803/12103.
MLA Handbook (7th Edition):
Sobota, Rafal Sebastian. “Genetics of Tuberculosis Resistance.” 2015. Web. 07 Mar 2021.
Vancouver:
Sobota RS. Genetics of Tuberculosis Resistance. [Internet] [Doctoral dissertation]. Vanderbilt University; 2015. [cited 2021 Mar 07].
Available from: http://hdl.handle.net/1803/12103.
Council of Science Editors:
Sobota RS. Genetics of Tuberculosis Resistance. [Doctoral Dissertation]. Vanderbilt University; 2015. Available from: http://hdl.handle.net/1803/12103
Vanderbilt University
7.
Bray, Michael Joseph.
Evaluating Epidemiologic and Genetic Risk Factors for Uterine Fibroid Characteristics.
Degree: PhD, Human Genetics, 2018, Vanderbilt University
URL: http://hdl.handle.net/1803/10965
► Uterine fibroids, benign tumors of the uterus, are the most common female pelvic tumor. Fibroids are highly heterogeneous, with some women developing a single small…
(more)
▼ Uterine fibroids, benign tumors of the uterus, are the most common female pelvic tumor. Fibroids are highly heterogeneous, with some women developing a single small fibroid while other women develop multiple and/or large fibroids. In addition, racial disparities in fibroid size and number support that fibroid characteristics have a genetic component. For example, African American (AA) women have more numerous and larger fibroids than European American (EA) women. Furthermore, AAs are two times more likely than EAs to receive surgical treatments for fibroids such as a hysterectomy. Unfortunately, most research on fibroids to date has not evaluated risk factors for specific fibroid characteristics. The purpose of this thesis is to provide a deeper understanding on both epidemiology and genetic risk factors of fibroid characteristics, fibroid number (single vs. multiple), volume of largest fibroid, and largest dimension of all fibroid measurements. After identifying epidemiologic risk factors for fibroid characteristics, this study identified several novel genetic loci associating with either fibroid size or number by methods of genome-wide association studies (GWAS) and admixture mapping studies. Lastly, this study estimated heritability of fibroids and fibroid size.
Advisors/Committee Members: Bingshan Li (committee member), Melissa F. Wellons (committee member), Todd L. Edwards (committee member), Nancy J. Cox (committee member), Digna R. Velez Edwards (committee member), David C. Samuels (Committee Chair).
Subjects/Keywords: admixture mapping study; genome-wide association study; uterine fibroids
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Bray, M. J. (2018). Evaluating Epidemiologic and Genetic Risk Factors for Uterine Fibroid Characteristics. (Doctoral Dissertation). Vanderbilt University. Retrieved from http://hdl.handle.net/1803/10965
Chicago Manual of Style (16th Edition):
Bray, Michael Joseph. “Evaluating Epidemiologic and Genetic Risk Factors for Uterine Fibroid Characteristics.” 2018. Doctoral Dissertation, Vanderbilt University. Accessed March 07, 2021.
http://hdl.handle.net/1803/10965.
MLA Handbook (7th Edition):
Bray, Michael Joseph. “Evaluating Epidemiologic and Genetic Risk Factors for Uterine Fibroid Characteristics.” 2018. Web. 07 Mar 2021.
Vancouver:
Bray MJ. Evaluating Epidemiologic and Genetic Risk Factors for Uterine Fibroid Characteristics. [Internet] [Doctoral dissertation]. Vanderbilt University; 2018. [cited 2021 Mar 07].
Available from: http://hdl.handle.net/1803/10965.
Council of Science Editors:
Bray MJ. Evaluating Epidemiologic and Genetic Risk Factors for Uterine Fibroid Characteristics. [Doctoral Dissertation]. Vanderbilt University; 2018. Available from: http://hdl.handle.net/1803/10965
Vanderbilt University
8.
Cummings, Anna Christine.
Exploring the genetic architecture of late-onset Alzheimer disease in an Amish population.
Degree: PhD, Human Genetics, 2012, Vanderbilt University
URL: http://hdl.handle.net/1803/14870
► Late-onset Alzheimer disease (LOAD) is a complex neurodegenerative disorder with a strong genetic component. APOE is a well-established risk gene for LOAD, and several other…
(more)
▼ Late-onset Alzheimer disease (LOAD) is a complex neurodegenerative disorder with a strong genetic component. APOE is a well-established risk gene for LOAD, and several other genes have also been identified. However, at least half of the genetic component for LOAD remains unexplained. Genetic heterogeneity complicates identifying the remaining risk genes. To overcome this problem the objective of my thesis work was to study the Amish communities of Ohio and Indiana, a genetically isolated founder population to identify a novel LOAD risk gene(s). I first performed quality control procedures on a set of genome-wide single nucleotide polymorphisms (SNPs) genotyped in the Amish. I then performed genome-wide linkage and association analyses in the cleaned dataset. Lastly, I performed a candidate gene sequence analysis.
Advisors/Committee Members: Jonathan L. Haines (committee member), William K. Scott (committee member), Michael G. Tramontana (committee member), Bingshan Li (committee member), Dana C. Crawford (Committee Chair).
Subjects/Keywords: Amish; Alzheimer disease; genetics
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Cummings, A. C. (2012). Exploring the genetic architecture of late-onset Alzheimer disease in an Amish population. (Doctoral Dissertation). Vanderbilt University. Retrieved from http://hdl.handle.net/1803/14870
Chicago Manual of Style (16th Edition):
Cummings, Anna Christine. “Exploring the genetic architecture of late-onset Alzheimer disease in an Amish population.” 2012. Doctoral Dissertation, Vanderbilt University. Accessed March 07, 2021.
http://hdl.handle.net/1803/14870.
MLA Handbook (7th Edition):
Cummings, Anna Christine. “Exploring the genetic architecture of late-onset Alzheimer disease in an Amish population.” 2012. Web. 07 Mar 2021.
Vancouver:
Cummings AC. Exploring the genetic architecture of late-onset Alzheimer disease in an Amish population. [Internet] [Doctoral dissertation]. Vanderbilt University; 2012. [cited 2021 Mar 07].
Available from: http://hdl.handle.net/1803/14870.
Council of Science Editors:
Cummings AC. Exploring the genetic architecture of late-onset Alzheimer disease in an Amish population. [Doctoral Dissertation]. Vanderbilt University; 2012. Available from: http://hdl.handle.net/1803/14870
Vanderbilt University
9.
Restrepo, Nicole Ann.
Investigation of the genetic epidemiology of age-related macular degeneration, primary open-angle glaucoma, and diabetic retinopathy in diverse populations.
Degree: PhD, Human Genetics, 2015, Vanderbilt University
URL: http://hdl.handle.net/1803/10956
► Common age, related eye diseases are a major driving force behind vision disability and blindness. The three most common diseases afflicting Americans today are age-related…
(more)
▼ Common age, related eye diseases are a major driving force behind vision disability and blindness. The three most common diseases afflicting Americans today are age-related macular degeneration (AMD), primary open-angle glaucoma (POAG), and diabetic retinopathy (DR). Much is known about the environmental factors contributing to disease risk and progression in these conditions, but the genetic architecture remains elusive. We performed a meta-analysis of known AMD-related variants and variants in cholesterol pathways in the three major race-ethnicities in the United States, and Chinese and Malay individuals from Singapore. Additionally, we identified potential novel associations between mitochondrial variants and risk of AMD in NHANES Mexican Americans. African American case and control samples for POAG and DR were extracted from the
Vanderbilt de-identified electronic medical records system called the “Synthetic Derivative.” A large subset of these individuals were genotyped on the Illumina Metabochip array. Genetic association analyses were performed to replicate previously identified and novel associations in patients with POAG and separately for patients with DR. Nominally significant associations ( p < 10-4) in POAG analyses suggest that vascular and angiogenic pathways may play a role in POAG risk in African Americans. In the study of DR, variants located in genes known to play a role in epithelial and endothelial tight cellular junctions, wound healing were nominally associated in the Synthetic Derivative African American DR population.
Advisors/Committee Members: Milam A. Brantley (committee member), Dana C. Crawford (committee member), Bingshan Li (committee member), Jonathan L. Haines (committee member), David J. Calkins (Committee Chair).
Subjects/Keywords: African American; diabetic retinopathy; primary open angle glaucoma; age-related macular degeneration; Mexican American
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Restrepo, N. A. (2015). Investigation of the genetic epidemiology of age-related macular degeneration, primary open-angle glaucoma, and diabetic retinopathy in diverse populations. (Doctoral Dissertation). Vanderbilt University. Retrieved from http://hdl.handle.net/1803/10956
Chicago Manual of Style (16th Edition):
Restrepo, Nicole Ann. “Investigation of the genetic epidemiology of age-related macular degeneration, primary open-angle glaucoma, and diabetic retinopathy in diverse populations.” 2015. Doctoral Dissertation, Vanderbilt University. Accessed March 07, 2021.
http://hdl.handle.net/1803/10956.
MLA Handbook (7th Edition):
Restrepo, Nicole Ann. “Investigation of the genetic epidemiology of age-related macular degeneration, primary open-angle glaucoma, and diabetic retinopathy in diverse populations.” 2015. Web. 07 Mar 2021.
Vancouver:
Restrepo NA. Investigation of the genetic epidemiology of age-related macular degeneration, primary open-angle glaucoma, and diabetic retinopathy in diverse populations. [Internet] [Doctoral dissertation]. Vanderbilt University; 2015. [cited 2021 Mar 07].
Available from: http://hdl.handle.net/1803/10956.
Council of Science Editors:
Restrepo NA. Investigation of the genetic epidemiology of age-related macular degeneration, primary open-angle glaucoma, and diabetic retinopathy in diverse populations. [Doctoral Dissertation]. Vanderbilt University; 2015. Available from: http://hdl.handle.net/1803/10956
Vanderbilt University
10.
Levinson, Rebecca Terrall.
The Phenotypic Consequences of Distinct Genetic Variation in an Electronic Medical Record.
Degree: PhD, Human Genetics, 2016, Vanderbilt University
URL: http://hdl.handle.net/1803/14698
► While genetic association studies have been able to elucidate the importance of genetics in human disease outcomes, these studies are limited by the necessity of…
(more)
▼ While genetic association studies have been able to elucidate the importance of genetics in human disease outcomes, these studies are limited by the necessity of collecting specifically tailored cohorts and that they frequently only test a single outcome. This focus on a single disease at a time ignores the interconnected nature of both biological pathways and disease phenotypes. My dissertation uses phenome-wide association scans (PheWAS), a method of testing one predictor for association with many disease outcomes, to expand our knowledge of multiple genetic variants and types of genetic variation. We used BioVU, a biobank linked to de-identified electronic medical records (EMRs), to explored a variety of applications for PheWAS. Each chapter presents a project where PheWAS was implemented as a starting point due to a specific hypothesis, before follow-up analyses based on the PheWAS outcome and out existing knowledge of the gene, protein, or variant were performed. The projects presented here begin with the most straight-forward scenario, directly genotyped single SNPs, and progress to imputed deletions before exploring ways to use PheWAS in multi-dimensional studies. In conclusion, I used PheWAS to uncover novel genotype-phenotype associations, and further explored these associations using other data types in the EMR. While PheWAS can be a useful tool for discovering unexpected disease consequences of genetic predictors, using it successfully requires sufficient knowledge of the genetic variation tested to evaluate the biological relevance of association signals
Advisors/Committee Members: Joshua C Denny (committee member), Bingshan Li (committee member), Douglas P Mortlock (committee member), David C Samuels (committee member), Melinda C Aldrich (Committee Chair).
Subjects/Keywords: PheWAS
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Levinson, R. T. (2016). The Phenotypic Consequences of Distinct Genetic Variation in an Electronic Medical Record. (Doctoral Dissertation). Vanderbilt University. Retrieved from http://hdl.handle.net/1803/14698
Chicago Manual of Style (16th Edition):
Levinson, Rebecca Terrall. “The Phenotypic Consequences of Distinct Genetic Variation in an Electronic Medical Record.” 2016. Doctoral Dissertation, Vanderbilt University. Accessed March 07, 2021.
http://hdl.handle.net/1803/14698.
MLA Handbook (7th Edition):
Levinson, Rebecca Terrall. “The Phenotypic Consequences of Distinct Genetic Variation in an Electronic Medical Record.” 2016. Web. 07 Mar 2021.
Vancouver:
Levinson RT. The Phenotypic Consequences of Distinct Genetic Variation in an Electronic Medical Record. [Internet] [Doctoral dissertation]. Vanderbilt University; 2016. [cited 2021 Mar 07].
Available from: http://hdl.handle.net/1803/14698.
Council of Science Editors:
Levinson RT. The Phenotypic Consequences of Distinct Genetic Variation in an Electronic Medical Record. [Doctoral Dissertation]. Vanderbilt University; 2016. Available from: http://hdl.handle.net/1803/14698
Vanderbilt University
11.
White, Marquitta Jonisse.
Genetics of Plasminogen Activator Inhibitor – 1: a potent biological effector of cardiovascular disease risk.
Degree: PhD, Human Genetics, 2014, Vanderbilt University
URL: http://hdl.handle.net/1803/14029
► Cardiovascular disease (CVD) is an inclusive term encompassing several disorders of the circulatory system that together account for the majority of global non-communicable disease (NCD)…
(more)
▼ Cardiovascular disease (CVD) is an inclusive term encompassing several disorders of the circulatory system that together account for the majority of global non-communicable disease (NCD) mortality. Major thrombotic events, due in part to impaired fibrinolysis, are a unifying characteristic of several CVDs. Plasminogen activator inhibitor-1 (PAI-1) is a major regulator of fibrinolysis, and PAI-1 levels associate with CVD susceptibility and severity in several populations. The main objectives of this dissertation were to evaluate the genetic impact of common single nucleotide polymorphisms (SNPs) on inter-individual variation in PAI-1 levels in a Ghanaian population, and present a novel method to identify candidate genes for prioritization in future studies. We discovered novel associations between single variants in the arylsulfatase b (ARSB), carboxypeptidase A2 (CPA2), and leukocyte receptor cluster member 9 (LENG9) and median PAI-1 levels. Quantile regression analyses directed at the upper quartile of the PAI-1 distribution was performed to uncover novel variants with significant impact on this clinically relevant portion of the PAI-1 distribution. Upper quartile regression analyses revealed significant associations between single variants in period circadian clock 3 (PER3), a discovery that supports previous evidence of the involvement of the circadian pathway in regulation of PAI-1 levels in Caucasian populations as well as model organisms. This finding suggests that the significance of the circadian pathway as a whole may be generalizable across populations, even though gene effects may be population specific. We present a novel approach; Multi-lOcus based selection of Candidate genes (MOCA), which incorporates multi-variant association signals into the prioritization of genes for further evaluation. MOCA identified four significantly associated loci; these loci included 28 novel candidate genes for PAI-1 levels. Each MOCA identified locus was located within previously identified CVD and/or PAI-1 related quantitative trait loci (QTL).
Advisors/Committee Members: Nancy J. Brown (committee member), melinda aldrich (committee member), Dana Crawford (committee member), Jason Moore (committee member), Scott M. Williams (committee member), Bingshan Li (Committee Chair).
Subjects/Keywords: population genetics; plasminogen activator inhibitor-1; cardiovascular disease
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
White, M. J. (2014). Genetics of Plasminogen Activator Inhibitor – 1: a potent biological effector of cardiovascular disease risk. (Doctoral Dissertation). Vanderbilt University. Retrieved from http://hdl.handle.net/1803/14029
Chicago Manual of Style (16th Edition):
White, Marquitta Jonisse. “Genetics of Plasminogen Activator Inhibitor – 1: a potent biological effector of cardiovascular disease risk.” 2014. Doctoral Dissertation, Vanderbilt University. Accessed March 07, 2021.
http://hdl.handle.net/1803/14029.
MLA Handbook (7th Edition):
White, Marquitta Jonisse. “Genetics of Plasminogen Activator Inhibitor – 1: a potent biological effector of cardiovascular disease risk.” 2014. Web. 07 Mar 2021.
Vancouver:
White MJ. Genetics of Plasminogen Activator Inhibitor – 1: a potent biological effector of cardiovascular disease risk. [Internet] [Doctoral dissertation]. Vanderbilt University; 2014. [cited 2021 Mar 07].
Available from: http://hdl.handle.net/1803/14029.
Council of Science Editors:
White MJ. Genetics of Plasminogen Activator Inhibitor – 1: a potent biological effector of cardiovascular disease risk. [Doctoral Dissertation]. Vanderbilt University; 2014. Available from: http://hdl.handle.net/1803/14029
. 
Open Access Theses and Dissertations