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University of Washington
1.
Brown, Lisa Anne.
Statistical Methods in Admixture Mapping: Mixed Model Based Testing and Genome-wide Significance Thresholds.
Degree: PhD, 2017, University of Washington
URL: http://hdl.handle.net/1773/38075 
► Genetic admixture occurs when two or more previously isolated populations combine to form an admixed population. The study of admixed populations can provide valuable insights…
(more)
▼ Genetic
admixture occurs when two or more previously isolated populations combine to form an admixed population. The study of admixed populations can provide valuable insights into the complex relationship between environmental exposures, genetic background and complex traits. Gene
mapping by linkage
admixture disequilibrium, or
admixture mapping, is a powerful approach for the identification of genetic loci influencing complex traits in ancestrally diverse populations.
Admixture mapping leverages genomic heterogeneity among sampled individuals for improved gene discovery, where genetic loci with unusual deviations in local ancestry and that are significantly associated with a trait are identified.
Admixture mapping can serve both as a primary method for discovery of novel genetic variants and as a complement to association
mapping. In this dissertation, we thoroughly investigate the performance of existing statistical methods used for
admixture mapping and we develop new methods that improve upon existing approaches. We also characterize the correlation structure of genetic loci in admixed populations and develop new genome-wide significance thresholds for
admixture mapping under a range of models that should be useful for the future studies. Using real genotyping data in a large sample of African Americans, we find evidence of assortative mating, and in simulation studies with simulated phenotypes, we demonstrate that ancestry-related assortative can induce genome-wide inflation of
admixture mapping test statistics and false positive associations. We also show how to appropriately adjust for this inflation and protect against spurious
admixture associations. Finally, new linear and logistic mixed model methodology is developed for
admixture mapping of quantitative and binary traits, respectively, in the presence of relatedness and population structure. We evaluate the performance of these methods through extensive simulation studies. The methods are applied to large-scale genetic studies of African American and Hispanic/Latino populations for genome-wide
admixture mapping analyses where novel candidate loci for a variety of biomedical traits are identified.
Advisors/Committee Members: Thornton, Timothy A (advisor), Browning, Sharon R (advisor).
Subjects/Keywords: admixed populations; admixture; admixture mapping; ancestry; mixed models; population structure; Genetics; Epidemiology; biostatistics
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APA (6th Edition):
Brown, L. A. (2017). Statistical Methods in Admixture Mapping: Mixed Model Based Testing and Genome-wide Significance Thresholds. (Doctoral Dissertation). University of Washington. Retrieved from http://hdl.handle.net/1773/38075
Chicago Manual of Style (16th Edition):
Brown, Lisa Anne. “Statistical Methods in Admixture Mapping: Mixed Model Based Testing and Genome-wide Significance Thresholds.” 2017. Doctoral Dissertation, University of Washington. Accessed April 22, 2021.
http://hdl.handle.net/1773/38075.
MLA Handbook (7th Edition):
Brown, Lisa Anne. “Statistical Methods in Admixture Mapping: Mixed Model Based Testing and Genome-wide Significance Thresholds.” 2017. Web. 22 Apr 2021.
Vancouver:
Brown LA. Statistical Methods in Admixture Mapping: Mixed Model Based Testing and Genome-wide Significance Thresholds. [Internet] [Doctoral dissertation]. University of Washington; 2017. [cited 2021 Apr 22].
Available from: http://hdl.handle.net/1773/38075.
Council of Science Editors:
Brown LA. Statistical Methods in Admixture Mapping: Mixed Model Based Testing and Genome-wide Significance Thresholds. [Doctoral Dissertation]. University of Washington; 2017. Available from: http://hdl.handle.net/1773/38075
Vanderbilt University
2.
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
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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 April 22, 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. 22 Apr 2021.
Vancouver:
Bray MJ. Evaluating Epidemiologic and Genetic Risk Factors for Uterine Fibroid Characteristics. [Internet] [Doctoral dissertation]. Vanderbilt University; 2018. [cited 2021 Apr 22].
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
3.
Jeff, Janina Maria.
Admixture mapping and subsequent finemapping suggests novel loci for type 2 diabetes in African Americans.
Degree: MS, Interdisciplinary Studies: Applied Statistics, 2012, Vanderbilt University
URL: http://hdl.handle.net/1803/15329
► Type 2 diabetes (T2D) is a complex metabolic disease that disproportionately affects African Americans. Obesity is a major risk factor for T2D, and it is…
(more)
▼ Type 2 diabetes (T2D) is a complex metabolic disease that disproportionately affects African Americans. Obesity is a major risk factor for T2D, and it is postulated that chronic inflammation possibly stemming from adipose tissue macrophages and T cells plays a key role. Genome-wide association studies (GWAS) have identified over 20 disease loci that contribute to T2D in European Americans but few studies have been performed in admixed populations.
We first performed a GWAS of 1,563 African Americans from the Vanderbilt Genome-Electronic Records Project and Northwestern University NUgene Project as part of the electronic Medical Records and Genomics (eMERGE) network. We successfully replicate an association in TCF7L2, previously identified by GWAS in our African American dataset. We were unable to identify novel associations at p<5.0x10-8 by GWAS.
Admixture mapping disease loci in recently admixed populations is a powerful method used to identify disease loci in African Americans. Using
admixture mapping, we sought to identify novel disease loci in the genome with T2D. Our
admixture scan revealed multiple candidate genes with T2D, including TCIRG1, a T-cell immune regulator expressed in the pancreas and liver and not previously implicated in T2D. We performed a subsequent fine-
mapping analysis to further assess the association with TCIRG1 and T2D in >5,000 African Americans. We successfully identified 13 independent associations in TCIRG1, CHKA, and ALDH3B1 genes on chromosome 11. Our results suggest a novel region on chromosome 11 identified by
admixture mapping associated with T2D in African Americans and warrants additional replication and validation in this region.
Advisors/Committee Members: Jonathan Haines (committee member), Dana Crawford (committee member).
Subjects/Keywords: admixture mapping; statistics; human genetics; type 2 diabetes
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APA (6th Edition):
Jeff, J. M. (2012). Admixture mapping and subsequent finemapping suggests novel loci for type 2 diabetes in African Americans. (Thesis). Vanderbilt University. Retrieved from http://hdl.handle.net/1803/15329
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Jeff, Janina Maria. “Admixture mapping and subsequent finemapping suggests novel loci for type 2 diabetes in African Americans.” 2012. Thesis, Vanderbilt University. Accessed April 22, 2021.
http://hdl.handle.net/1803/15329.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Jeff, Janina Maria. “Admixture mapping and subsequent finemapping suggests novel loci for type 2 diabetes in African Americans.” 2012. Web. 22 Apr 2021.
Vancouver:
Jeff JM. Admixture mapping and subsequent finemapping suggests novel loci for type 2 diabetes in African Americans. [Internet] [Thesis]. Vanderbilt University; 2012. [cited 2021 Apr 22].
Available from: http://hdl.handle.net/1803/15329.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Jeff JM. Admixture mapping and subsequent finemapping suggests novel loci for type 2 diabetes in African Americans. [Thesis]. Vanderbilt University; 2012. Available from: http://hdl.handle.net/1803/15329
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Penn State University
4.
Pearson, Laurel.
Genetic Contributions to Disparities in Preterm Birth Among African-American Women.
Degree: 2012, Penn State University
URL: https://submit-etda.libraries.psu.edu/catalog/15444
► In the United States African-American women experience the poorest pregnancy outcomes of any ethnic group. Compared to European-American women, African-American women have a substantially greater…
(more)
▼ In the United States African-American women experience the poorest pregnancy outcomes of any ethnic group. Compared to European-American women, African-American women have a substantially greater risk of preterm birth, low birth weight neonates, and infant mortality. A variety of factors have been hypothesized to contribute to disparities in these complex pregnancy phenotypes including environment, lifestyle, and genetics. This dissertation investigates genetic ancestry and the role of genes in contributing to risk of poor pregnancy outcomes among African-American women.
In the first portion of this research the association between West African genomic ancestry and birth weight and the association between genomic ancestry, skin pigmentation, and serum vitamin D level were investigated. Increasing West African ancestry was found to be significantly associated with lower birth weight in female neonates and was inversely correlated with serum vitamin D level.
For the next phase of this project,
admixture mapping was used to identify novel regions of the genome that are associated with preterm birth due to preterm premature rupture of membranes (PPROM). In this case-control analysis of African-American neonates, regions on five chromosomes (5, 8, 11, 19, and 21) were identified to be associated with increased risk. These regions provide areas for future research into the genetic contributions to risk of preterm birth due to PPROM.
In the final portion of this research, 90 previously reported preterm birth candidate genes were tested for signatures of accelerated evolution. Using three test statistics in the parental populations that contribute to African-American
admixture, European and West African, forty-four of the preterm birth candidate genes had evidence of non-neutral evolution. This analysis helped prioritize genes that are more likely to contribute to the increased risk of preterm birth in African-American women compared to European-American women.
Future work will include a replication of the
admixture mapping study to refine the chromosomal regions found to be associated with risk of preterm birth due to PPROM. Additionally, genotyping of the forty-four preterm birth candidate genes nominated by the three tests for accelerated evolution is planned to look for risk alleles that contribute to the disparity in preterm birth among African-American women.
Advisors/Committee Members: Mark Shriver, Dissertation Advisor/Co-Advisor, David John Vandenbergh, Committee Chair/Co-Chair, Kenneth Monrad Weiss, Committee Member, Nina G Jablonski, Committee Member, Jerome Strauss Iii, Special Member.
Subjects/Keywords: Preterm Birth; Admixture Mapping; Accelerated Evolution; African American; PPROM; Health Disparities
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APA ·
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CSE |
Export
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Manager
APA (6th Edition):
Pearson, L. (2012). Genetic Contributions to Disparities in Preterm Birth Among African-American Women. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/15444
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Pearson, Laurel. “Genetic Contributions to Disparities in Preterm Birth Among African-American Women.” 2012. Thesis, Penn State University. Accessed April 22, 2021.
https://submit-etda.libraries.psu.edu/catalog/15444.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Pearson, Laurel. “Genetic Contributions to Disparities in Preterm Birth Among African-American Women.” 2012. Web. 22 Apr 2021.
Vancouver:
Pearson L. Genetic Contributions to Disparities in Preterm Birth Among African-American Women. [Internet] [Thesis]. Penn State University; 2012. [cited 2021 Apr 22].
Available from: https://submit-etda.libraries.psu.edu/catalog/15444.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Pearson L. Genetic Contributions to Disparities in Preterm Birth Among African-American Women. [Thesis]. Penn State University; 2012. Available from: https://submit-etda.libraries.psu.edu/catalog/15444
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Penn State University
5.
Matthes, Kerri Allison.
A Preliminary Genetic Investigation of Normal Variation in Facial Features
.
Degree: 2008, Penn State University
URL: https://submit-etda.libraries.psu.edu/catalog/8247
► Variation in facial features between populations has arisen over time due to differing evolutionary forces acting on populations, resulting in allele frequency and phenotypic differences.…
(more)
▼ Variation in facial features between populations has arisen over time due to differing evolutionary forces acting on populations, resulting in allele frequency and phenotypic differences. Investigating variation in facial morphology can provide a more thorough understanding of these evolutionary forces and can also be used to identify genes involved in normal facial feature variation. This study aims to elucidate preliminary genetic relationships between ancestry, facial morphology and candidate genes that may play a role in morphological variation. Because admixed populations are well suited for studying traits that differ between two parental populations, a sample of African Americans were chosen for investigation in this study. The maximum likelihood genetic ancestry for 131 participants, ages 18-37, was obtained using 176 ancestry informative markers to determine their proportions of European and West African ancestry. Using 3dMDface (Atlanta, GA) imaging and analysis software, 3-dimensional images of each participant were captured and landmarked at 22 standard anthropometric locations. These coordinates were compared using a Euclidean Distance Matrix Analysis to identify morphological trait variations within the sample. DNA from each participant was genotyped at a polymorphic site in seven different selection-nominated candidate genes known to be involved in genetic disorders with craniofacial phenotypes. WinEDMA Form comparison between West African and European pseudo-parental groups of the same sex revealed interlandmark distances that vary significantly between the parental populations. Similar results were obtained using an ANOVA on linear distances calculated from the landmark coordinates in the entire study sample of 131 individuals of varying
admixture proportion. Regression analyses identified correlations between the absolute distance (in mm) between the landmarks and proportion of West African ancestry after adjustment for variation due to sex and height. Many interlandmark distances showed highly significant relationships with genetic ancestry which were in some cases stronger (R2 = 0.337) than those previously identified between skin color and West African ancestry proportion (R2 = 0.211). ANOVAs were conducted using each candidate gene in combination with each interlandmark distance using sex, height and ancestry as covariates. Five out of seven candidate genes returned significant results, identifying trends of significance across regions of the face. COL11A1 shows association with normal variation around the mouth. FGFR2 appears to be associated with face length. TRPS1 displays a slight association with variation around the eyes and brow ridge. LMNA has a striking association with projection of the face. BRAF shows association with variation regarding the nose, notably with nose width. Landmarking trials conducted by independent observers returned similar results, with comparable trends. The directionality of morphological change was investigated using ƒÒƒz the regression…
Advisors/Committee Members: Mark Shriver, Thesis Advisor/Co-Advisor.
Subjects/Keywords: admixture mapping; craniofacial morphology; candidate genes
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APA ·
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Manager
APA (6th Edition):
Matthes, K. A. (2008). A Preliminary Genetic Investigation of Normal Variation in Facial Features
. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/8247
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Matthes, Kerri Allison. “A Preliminary Genetic Investigation of Normal Variation in Facial Features
.” 2008. Thesis, Penn State University. Accessed April 22, 2021.
https://submit-etda.libraries.psu.edu/catalog/8247.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Matthes, Kerri Allison. “A Preliminary Genetic Investigation of Normal Variation in Facial Features
.” 2008. Web. 22 Apr 2021.
Vancouver:
Matthes KA. A Preliminary Genetic Investigation of Normal Variation in Facial Features
. [Internet] [Thesis]. Penn State University; 2008. [cited 2021 Apr 22].
Available from: https://submit-etda.libraries.psu.edu/catalog/8247.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Matthes KA. A Preliminary Genetic Investigation of Normal Variation in Facial Features
. [Thesis]. Penn State University; 2008. Available from: https://submit-etda.libraries.psu.edu/catalog/8247
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Southern California
6.
Liu, Jinghua.
Population substructure and its impact on genome-wide
association studies with admixed populations.
Degree: PhD, Statistical Genetics and Genetic
Epidemiology, 2012, University of Southern California
URL: http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll3/id/78608/rec/5120
► Association studies among admixed populations pose many challenges. The purpose of this study is to compare the methods for ancestry estimation and to investigate the…
(more)
▼ Association studies among admixed populations pose
many challenges. The purpose of this study is to compare the
methods for ancestry estimation and to investigate the control for
confounding and the capture of heterogeneity in SNP effect by the
use of individual ancestries. In addition, a general regression
framework is proposed to perform
admixture mapping for both
case-only and case-control study designs among admixed populations.
For confounding and heterogeneity, simulation results indicate that
1) adjustment for global ancestry can control for confounding; 2)
additional adjustment for local ancestry may increase power when
the induced
admixture LD is in the opposite direction as the LD in
the ancestral populations; 3) the inclusion of a SNP by local
ancestry interaction term can increase power when there is
substantial differential LD between ancestry populations. Real data
analysis in a genome-wide data using the University of Southern
California's Children's Health Study of childhood asthma highlights
rs10519951 (p=8.5E-7) from the model with the interaction term, a
SNP lacking any evidence of association from the SNP association
analysis (p=0.5). For the
admixture mapping, simulation and real
data analysis results among African Americans from the Multiethnic
Cohort Study of prostate cancer indicate that 1) case-only analysis
suffers from spurious results among the regions with biased local
ancestry estimation; 2) our proposed regression model yield similar
performance as the existing methods; 3) it is more powerful to
incorporate genotype information for
admixture mapping; 4) and it
is more powerful to incorporate SNP by local ancestry interaction
to capture the
admixture signal and heterogeneity by local ancestry
simultaneously.
Advisors/Committee Members: Conti, David V. (Committee Chair), Gilliland, Frank D. (Committee Member), Gauderman, William James (Committee Member), Thomas, Duncan C. (Committee Member), Knowles, James (Committee Member).
Subjects/Keywords: genetic association study; GWAS; admixture mapping; population stratification; confounding; heterogeneity; admixed population
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APA ·
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MLA ·
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Manager
APA (6th Edition):
Liu, J. (2012). Population substructure and its impact on genome-wide
association studies with admixed populations. (Doctoral Dissertation). University of Southern California. Retrieved from http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll3/id/78608/rec/5120
Chicago Manual of Style (16th Edition):
Liu, Jinghua. “Population substructure and its impact on genome-wide
association studies with admixed populations.” 2012. Doctoral Dissertation, University of Southern California. Accessed April 22, 2021.
http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll3/id/78608/rec/5120.
MLA Handbook (7th Edition):
Liu, Jinghua. “Population substructure and its impact on genome-wide
association studies with admixed populations.” 2012. Web. 22 Apr 2021.
Vancouver:
Liu J. Population substructure and its impact on genome-wide
association studies with admixed populations. [Internet] [Doctoral dissertation]. University of Southern California; 2012. [cited 2021 Apr 22].
Available from: http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll3/id/78608/rec/5120.
Council of Science Editors:
Liu J. Population substructure and its impact on genome-wide
association studies with admixed populations. [Doctoral Dissertation]. University of Southern California; 2012. Available from: http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll3/id/78608/rec/5120
Vanderbilt University
7.
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
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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 April 22, 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. 22 Apr 2021.
Vancouver:
Giri A. Modifiable and non-modifiable risk factors for pelvic organ prolapse. [Internet] [Doctoral dissertation]. Vanderbilt University; 2015. [cited 2021 Apr 22].
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
8.
Shetty, Priya Bhatia.
Genetic Epidemiology of Hypertension in Populations:
Applications of Modified Methods.
Degree: PhD, Epidemiology and Biostatistics, 2014, Case Western Reserve University School of Graduate Studies
URL: http://rave.ohiolink.edu/etdc/view?acc_num=case1385562333
► Objective: Modified methods of analysis were applied in three studies of African-Americans to identify variants associated with blood pressure and to address missing heritability in…
(more)
▼ Objective: Modified methods of analysis were applied
in three studies of African-Americans to identify variants
associated with blood pressure and to address missing heritability
in genetic studies of hypertension. Methods: Three genetic
epidemiology studies were conducted in African-American subjects in
the National Heart, Lung and Blood Institute’s Family Blood
Pressure Program. First, a candidate gene association study using
gene scores was conducted in genomic regions that previously showed
admixture association evidence for blood pressure and other
cardiovascular traits. Second,
admixture mapping analyses were
conducted on the 22 autosomal chromosomes for blood pressure and
lipids, followed by fine-
mapping analyses of the suggestive
admixture regions in families. Third,
admixture mapping analyses
were conducted for blood pressure in subjects treated with at least
2 anti-hypertensive medications, and the regions suggesting
admixture evidence were followed up with fine-
mapping analyses in
families to identify variants associated with apparent
treatment-resistant hypertension. Stratified analyses were
conducted by number of drugs for phenotypes showing significant
association results in all subjects. Results: In the first study,
CXADR and F2RL1 were associated with blood pressure and
body-mass-index, respectively. Analysis of local ancestry suggested
that other associated SNPs were present in these regions. In the
second study, the
admixture mapping analyses identified seven
regions associated with blood pressure and lipids. In the
fine-
mapping analyses, 11 SNPs in 8 independent loci were
identified for associations with lipids. In the third study,
admixture regions on chromosomes 3 and 5 were identified for
association with blood pressure in all treated subjects and in
subjects taking two anti-hypertensive drugs, respectively. The
regions included variants that were previously identified in a
large blood pressure GWAS, and the results suggested that the
variants were associated with treatment response, rather than blood
pressure, in African-Americans. Conclusions: A number of novel and
known genomic and genetic variants were identified for blood
pressure and other cardiovascular phenotypes. The methods of
analysis were modified to incorporate gene scores, two-stage study
designs and fine-
mapping association analyses in families, and
these adaptations were key in addressing some of the missing
heritability in the genetics of hypertension and other
cardiovascular traits.
Advisors/Committee Members: Zhu, Xiaofeng (Advisor).
Subjects/Keywords: Epidemiology; Genetics; genetic epidemiology; admixture mapping analysis; candidate gene analysis; African-Americans; blood pressure; cardiovascular disease
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APA (6th Edition):
Shetty, P. B. (2014). Genetic Epidemiology of Hypertension in Populations:
Applications of Modified Methods. (Doctoral Dissertation). Case Western Reserve University School of Graduate Studies. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=case1385562333
Chicago Manual of Style (16th Edition):
Shetty, Priya Bhatia. “Genetic Epidemiology of Hypertension in Populations:
Applications of Modified Methods.” 2014. Doctoral Dissertation, Case Western Reserve University School of Graduate Studies. Accessed April 22, 2021.
http://rave.ohiolink.edu/etdc/view?acc_num=case1385562333.
MLA Handbook (7th Edition):
Shetty, Priya Bhatia. “Genetic Epidemiology of Hypertension in Populations:
Applications of Modified Methods.” 2014. Web. 22 Apr 2021.
Vancouver:
Shetty PB. Genetic Epidemiology of Hypertension in Populations:
Applications of Modified Methods. [Internet] [Doctoral dissertation]. Case Western Reserve University School of Graduate Studies; 2014. [cited 2021 Apr 22].
Available from: http://rave.ohiolink.edu/etdc/view?acc_num=case1385562333.
Council of Science Editors:
Shetty PB. Genetic Epidemiology of Hypertension in Populations:
Applications of Modified Methods. [Doctoral Dissertation]. Case Western Reserve University School of Graduate Studies; 2014. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=case1385562333
Penn State University
9.
Zaidi, Syed.
Evolutionary Inference of the Human Facial Form: Insights from the Genotype-Phenotype Interface.
Degree: 2016, Penn State University
URL: https://submit-etda.libraries.psu.edu/catalog/2v23vt37b
► The human face contains important organs which perform vital functions such as eating and breathing, sensory functions such as seeing and smelling, as well as…
(more)
▼ The human face contains important organs which perform vital functions such as eating and breathing, sensory functions such as seeing and smelling, as well as signaling sex, emotions, and identity. It is also quite variable within and across human populations. Very little is known about the evolution of facial shape in humans, or the genetic architecture underlying the development of facial shape. In this dissertation, I have investigated the evolutionary genetics of certain aspects of the three-dimensional shape of the human face. In chapter one, I provide a literature review of the various hypotheses regarding the evolution of facial shape and the current evidence supporting them. In chapter two, I used a quantitative genetic framework to test the hypothesis that human variation in the shape of the nose seems to have been influenced by local adaptation to temperature. The results from this chapter suggest that the evolution of certain aspects of human nose shape, such as nostril size and nasal ridge may have been driven by local adaptation to temperature. In chapter three, I used an
admixture mapping approach to identify three genomic loci associated with nose shape variation in a sample of individuals with mixed African and European ancestry. The nearest genes to the
admixture peaks are LHX8 (LIM Homeobox 8), MITF (Micropthalmia-associated transcription factor), and, UACA (Uveal autoantigen with coiled-coil domains and ankyrin repeats). Chapter four is an investigation in the effects of genetic heterozygosity on traits such as facial asymmetry, facial masculinity, and height, which are thought to signal genetic quality and immunocompetence. Finally, in chapter five, I discuss the evolutionary implications of these results and future directions for this research.
Advisors/Committee Members: Mark Shriver, Dissertation Advisor/Co-Advisor.
Subjects/Keywords: face; facial shape; nose; population genetics; selection; evolution; admixture mapping; climate; quantitative genetics; geometric morphometrics; 3D; Fst; facial asymmetry; facial masculinity; sexual selection; heterozygosity; MHC
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APA ·
Chicago ·
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CSE |
Export
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APA (6th Edition):
Zaidi, S. (2016). Evolutionary Inference of the Human Facial Form: Insights from the Genotype-Phenotype Interface. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/2v23vt37b
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Zaidi, Syed. “Evolutionary Inference of the Human Facial Form: Insights from the Genotype-Phenotype Interface.” 2016. Thesis, Penn State University. Accessed April 22, 2021.
https://submit-etda.libraries.psu.edu/catalog/2v23vt37b.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Zaidi, Syed. “Evolutionary Inference of the Human Facial Form: Insights from the Genotype-Phenotype Interface.” 2016. Web. 22 Apr 2021.
Vancouver:
Zaidi S. Evolutionary Inference of the Human Facial Form: Insights from the Genotype-Phenotype Interface. [Internet] [Thesis]. Penn State University; 2016. [cited 2021 Apr 22].
Available from: https://submit-etda.libraries.psu.edu/catalog/2v23vt37b.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Zaidi S. Evolutionary Inference of the Human Facial Form: Insights from the Genotype-Phenotype Interface. [Thesis]. Penn State University; 2016. Available from: https://submit-etda.libraries.psu.edu/catalog/2v23vt37b
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Penn State University
10.
Halder, Indrani.
MEASURING AND USING INDIVIDUAL GENOMIC ANCESTRY TO STUDY COMPLEX PHENOTYPES.
Degree: 2008, Penn State University
URL: https://submit-etda.libraries.psu.edu/catalog/6772
► Several complex diseases show population specific differences the causes for which are as yet unknown. Examples of such diseases include obesity and non insulin dependent…
(more)
▼ Several complex diseases show population specific differences the causes for which are as yet unknown. Examples of such diseases include obesity and non insulin dependent diabetes which are more prevalent in African American, Indigenous American and Latino populations compared to European Americans. Dementia and Osteoporosis are examples of diseases which are more prevalent in European Americans. It is obvious from these examples that the differences follow broad racial or ethnic categories and because of this correlation, medical research has focused extensively on investigating racial or ethnic differences in disease risk. The concept of ‘Race’ is multifaceted and any simplistic annotation is insufficient, may be even wrong, unless we make attempts to decompose the different aspects of race and use them appropriately in the context of biomedical research. Broadly speaking, race has two distinct components. The biological component referred to as Biogeographical ancestry; and the sociocultural component which reflects the ethnic heritage of an individual. Anthropological and genetic research in the past couple of decades has shown that the concept of typological races is scientifically obsolete yet the idea lives on and is used in biomedical research. Race/Ethnicity is still used as a classifier to establish and highlight population specific differences, while often inter-individual variation within a specific racial/ethnic category is ignored.
Anthropological research has shown that anatomically modern humans originated in Africa, and migrated to different parts of the world. Over the course of time, continental populations were established and for a period, large scale interactions between continental populations were limited. Given the recent and common origin, most genomic regions in all continental populations are very similar. At some loci, however, there has been some change in allele frequencies in the time since the separation of populations. In the past few centuries, there have been large scale migrations, voluntary or forced, that gave rise to populations of “mixed” ancestry. And at those loci where allele frequencies differed between continental populations, this has resulted in long range non random association in the admixed population. Many US residents can trace their genetic ancestry to more than one continent. The European colonial period that started in the late 1400s brought together in the New World, populations that had been geographically isolated, namely, Europeans, West Africans and Indigenous Americans. The impact of this was two fold, biological, which resulted in genes from different ancestral populations coming together in varying proportions in the different admixed populations and also cultural, in that certain ways of life of one population were adopted by another. Thus, the differences in disease prevalence which appear to follow broad racial categories could have been influenced by both genetic and non genetic factors (including environmental, sociocultural and behavioral…
Advisors/Committee Members: Mark Shriver, Committee Chair/Co-Chair, Kenneth Monrad Weiss, Committee Chair/Co-Chair, Hiroshi Akashi, Committee Member, Kateryna Dmytrivna Makova, Committee Member, Esteban J Parra, Committee Member.
Subjects/Keywords: Genomic ancestry; individual ancestry estimation; population stratification; admixture mapping; complex diseases; racial/ethnic differences in disease risk
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APA ·
Chicago ·
MLA ·
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CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Halder, I. (2008). MEASURING AND USING INDIVIDUAL GENOMIC ANCESTRY TO STUDY COMPLEX PHENOTYPES. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/6772
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Halder, Indrani. “MEASURING AND USING INDIVIDUAL GENOMIC ANCESTRY TO STUDY COMPLEX PHENOTYPES.” 2008. Thesis, Penn State University. Accessed April 22, 2021.
https://submit-etda.libraries.psu.edu/catalog/6772.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Halder, Indrani. “MEASURING AND USING INDIVIDUAL GENOMIC ANCESTRY TO STUDY COMPLEX PHENOTYPES.” 2008. Web. 22 Apr 2021.
Vancouver:
Halder I. MEASURING AND USING INDIVIDUAL GENOMIC ANCESTRY TO STUDY COMPLEX PHENOTYPES. [Internet] [Thesis]. Penn State University; 2008. [cited 2021 Apr 22].
Available from: https://submit-etda.libraries.psu.edu/catalog/6772.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Halder I. MEASURING AND USING INDIVIDUAL GENOMIC ANCESTRY TO STUDY COMPLEX PHENOTYPES. [Thesis]. Penn State University; 2008. Available from: https://submit-etda.libraries.psu.edu/catalog/6772
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
11.
Gopalakrishnan, Shyam S.
Methods for statistical and population genetics analyses.
Degree: PhD, Biostatistics, 2011, University of Michigan
URL: http://hdl.handle.net/2027.42/89609
► Genetics studies have advanced rapidly, from candidate region studies to genome wide association studies (GWAS) and next generation sequencing projects. The emergence of new technologies…
(more)
▼ Genetics studies have advanced rapidly, from candidate region studies to genome wide association studies (GWAS) and next generation sequencing projects. The emergence of new technologies has brought with it an array of statistical challenges. In this thesis, we propose methods for statistical and population genetics in our effort to better understand the underlying architecture of our genomes.
GWAS rely on indirect association, testing a reduced set of representative markers (tagSNPs) instead of all variants present in the genome. In the first chapter, we propose a graph-based method to select the optimal set of tagSNPs. We apply our method to chromosome-wide data and show that it outperforms the widely used greedy approach, selecting fewer tagSNPs while maintaining high correlation with non-tagSNPs variants.
Alignment to a reference sequence is an integral step in many sequencing studies. Multiply mapped reads, reads that align to multiple locations in the reference, are discarded from downstream analyses, resulting in a loss of information. We develop a Gibbs sampling approach to identify the true location of multiply mapped reads obtained from the alignment step. We validate our method using simulation studies. We use the improvement in variant discovery to quantify the effect of including multiply mapped reads in downstream analyses.
In the third chapter, we explore the feasibility of
admixture mapping, a population genetics tool, in identifying regions harboring rare susceptibility variants. We compare the power of
admixture mapping to single marker association studies in detecting causal regions. We find that
admixture mapping performs better over a wide range of risk allele frequencies.
The site frequency spectrum (SFS) is an important summary statistic in population genetics, encompassing information on selection and demographic history. We show that estimates of the SFS obtained from genotype calling methods underestimate the number of rare variants, especially singletons and doubletons. We derive a maximum likelihood estimate for the SFS. We demonstrate that our method performs better than SFS obtained from genotype calling algorithms using both simulated and real data examples.
Advisors/Committee Members: Zoellner, Sebastian K. (committee member), Boehnke, Michael Lee (committee member), Li, Jun (committee member), Qin, Zhaohui (committee member), Rosenberg, Noah A. (committee member).
Subjects/Keywords: Statistical Genetics; Population Genetics; Admixture Mapping; Site Frequency Spectrum Estimation; TagSNP Selection; Next Generation Sequence Read Remapping; Genetics; Statistics and Numeric Data; Health Sciences; Science
…correcting for 1 million tests. 51
4.4
Contour plot showing the power of admixture mapping… …57
The relationship between power of admixture mapping and contribution to prevalence in… …59
3.1
4.5
4.6
vii
4.7
Power of admixture mapping compared to the power of single… …cases and controls each.
60
Power of admixture mapping compared to indirect association… …Admixture mapping to identify rare variants
An admixed population derives its ancestry from…
Record Details
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Record Details
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Gopalakrishnan, S. S. (2011). Methods for statistical and population genetics analyses. (Doctoral Dissertation). University of Michigan. Retrieved from http://hdl.handle.net/2027.42/89609
Chicago Manual of Style (16th Edition):
Gopalakrishnan, Shyam S. “Methods for statistical and population genetics analyses.” 2011. Doctoral Dissertation, University of Michigan. Accessed April 22, 2021.
http://hdl.handle.net/2027.42/89609.
MLA Handbook (7th Edition):
Gopalakrishnan, Shyam S. “Methods for statistical and population genetics analyses.” 2011. Web. 22 Apr 2021.
Vancouver:
Gopalakrishnan SS. Methods for statistical and population genetics analyses. [Internet] [Doctoral dissertation]. University of Michigan; 2011. [cited 2021 Apr 22].
Available from: http://hdl.handle.net/2027.42/89609.
Council of Science Editors:
Gopalakrishnan SS. Methods for statistical and population genetics analyses. [Doctoral Dissertation]. University of Michigan; 2011. Available from: http://hdl.handle.net/2027.42/89609
. 
Open Access Theses and Dissertations
