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A GENOME WIDE ASSOCIATION STUDY OF MULTIPLE SCLEROSIS (MS)
IN HISPANICS
by
Shengzhi Wang
A Dissertation Presented to the
FACULTY OF THE USC GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
MASTER OF SCIENCE
(BIOSTATISTICS)
Aug 2013
Copyright 2013 Shengzhi Wang
Object Description
| Title | A genome wide association study of multiple sclerosis (MS) in Hispanics |
| Author | Wang, Shengzhi |
| Author email | wszcas@gmail.com;shengzhi.wang@gmail.com |
| Degree | Master of Science |
| Document type | Thesis |
| Degree program | Biostatistics |
| School | Keck School of Medicine |
| Date defended/completed | 2013-06-21 |
| Date submitted | 2013-07-16 |
| Date approved | 2013-07-16 |
| Restricted until | 2013-07-16 |
| Date published | 2013-07-16 |
| Advisor (committee chair) | Conti, David V. |
| Advisor (committee member) |
Gauderman, William James Cozen, Wendy Amezcua, Lilyana |
| Abstract | Genetic factors are postulated to contribute to the difference of susceptibility as well as clinical outcomes of multiple sclerosis (MS) in different populations. The Hispanic population offers a unique potential to identify novel genetic variants involved in differential disease presentation of MS (e.g. the site of lesions in the central nervous system, opticospinal (OSMS) vs classical MS) due to the genetic diversities in this admixed population. While MS overall is more common in Whites of European ancestry, if and how the heterogeneity of genetic admixture in Hispanics contributes to characteristics of the disease is unknown. ❧ Methods: 127 Hispanics with MS were genotyped and their global ancestries were estimated. They were then classified into either classical MS or OSMS based on clinical and radiological assessment. For statistical testing of the association of genetic ancestry to OSMS vs. classical MS and to clinical characteristics, linear regression or t-tests were used for continuous outcomes and logistic regression or chi-square tests were used for binary outcomes. For the genome-wide investigation of SNP associations, logistic regression was used with adjustment by age, gender and global ancestry to control for potential confounding due to population admixture. The Wald test is used to determine the statistical significance. ❧ Results: For the 142 MS patients participated in the study, Asian characteristic of the disease, such as OSMS was noted in 25 patients (17.6% of total patients) while classical MS was observed in 102 patients (71.8% of the total patients). There was no significant difference of age, gender, ethnicity, migration history, age at diagnosis or disease duration between OSMS and classical MS patients. However, increased disability was significantly noted in OSMS patients (Mean score of disability measurement ±SD, 4.64±2.05) as compared to classical MS patients (2.47±1.92) (p=3.0e-05). In addition, age at the first symptom onset is significantly younger in OSMS (26.36±11.6) compared with classical MS (31.47±11.9) (p=0.057). Interestingly, the migration history of the patients (early migration vs late migration) as well as their neurological disability severity (EDSS score) are statistically significant associated with the risk of OSMS as compared to classical MS (odds ratio=3.63, p value=0.055 for migration history and odds ratio=1.99, p value<0.001 for disability severity). Global ancestry estimation showed that both European and Asian genetic ancestries were the most common background followed by African in these Hispanic MS patients. No significant difference of these ancestry proportions were found between OSMS and classical MS. Logistic regression modeling suggest that European ancestry is negatively associated with the risk of OSMS as compared to classical MS (OR=0.063, 95% confidence interval (0.001, 2.598)) after adjusting for EDSS and age of 1st symptom onset. However, this association is not statistically significant based on current model estimation (p=0.152). Finally as a pilot investigation, to identify genomic regions associated with risk of OSMS, we performed a genome wide scan comparing OSMS patients vs classical MS patients. None of the SNPs have p values surpassing the genome wide level significance threshold (5 x 10⁻⁸). The top SNPs with lowest p values (around 1x10⁻⁵) are discussed for their potential involvement in the odds of OSMS vs classical MS. ❧ Conclusion: The results presented in this study provide pilot data to address whether and how the heterogeneity of genetic admixture in Hispanics contributes to characteristics of the MS. The GWAS result serves as an initial point which needs to be expanded as more patients are recruited into the study in the future to increase the power of detecting genomic regions that are associated with the differential MS presentations. |
| Keyword | multiple sclerosis; genome wide association study; Hispanics; logistic regression |
| Language | English |
| Part of collection | University of Southern California dissertations and theses |
| Publisher (of the original version) | University of Southern California |
| Place of publication (of the original version) | Los Angeles, California |
| Publisher (of the digital version) | University of Southern California. Libraries |
| Provenance | Electronically uploaded by the author |
| Type | texts |
| Legacy record ID | usctheses-m |
| Contributing entity | University of Southern California |
| Rights | Wang, Shengzhi |
| Physical access | The author retains rights to his/her dissertation, thesis or other graduate work according to U.S. copyright law. Electronic access is being provided by the USC Libraries in agreement with the author, as the original true and official version of the work, but does not grant the reader permission to use the work if the desired use is covered by copyright. It is the author, as rights holder, who must provide use permission if such use is covered by copyright. The original signature page accompanying the original submission of the work to the USC Libraries is retained by the USC Libraries and a copy of it may be obtained by authorized requesters contacting the repository e-mail address given. |
| Repository name | University of Southern California Digital Library |
| Repository address | USC Digital Library, University of Southern California, University Park Campus MC 7002, 106 University Village, Los Angeles, California 90089-7002, USA |
| Repository email | cisadmin@lib.usc.edu |
| Filename | etd-WangShengz-1783.pdf |
| Archival file | uscthesesreloadpub_Volume3/etd-WangShengz-1783.pdf |
Description
| Title | Page 1 |
| Contributing entity | University of Southern California |
| Repository email | cisadmin@lib.usc.edu |
| Full text | A GENOME WIDE ASSOCIATION STUDY OF MULTIPLE SCLEROSIS (MS) IN HISPANICS by Shengzhi Wang A Dissertation Presented to the FACULTY OF THE USC GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirements for the Degree MASTER OF SCIENCE (BIOSTATISTICS) Aug 2013 Copyright 2013 Shengzhi Wang |
