한국인 집단에서의 혈중 중성지방 농도에 대한 분자 및 유전적 분석 및 성인 신장 전장유전체 분석
Molecular and genetic basis of plasma triglyceride level variation and genome-wide association study for adult height in Korean population
- 주제(키워드) GWAS , Triglyceride , ApoA5 , KoGES , Height
- 발행기관 아주대학교
- 지도교수 최상돈
- 발행년도 2019
- 학위수여년월 2019. 8
- 학위명 박사
- 학과 및 전공 일반대학원 분자과학기술학과
- 실제URI http://www.dcollection.net/handler/ajou/000000029204
- 본문언어 영어
- 저작권 아주대학교 논문은 저작권에 의해 보호받습니다.
초록/요약
Every human being has a personal difference, and Genome-wide association studies (GWAS) is significantly advanced the way to describe the complex human trait. Thus, the Korean genome and epidemiology study with large scale genome data was prepared for showing Korean specific genetic variants. This research aims to discover which polymorphism affects the quantitative trait such as plasma triglyceride and adult height. Under KARE and HEXA studies, it has been studied a suite of biomarkers that have been reported for association with plasma triglyceride and adult height. Particularly, it has been sought to estimate the following three broad aspects: 1. what are the risk alleles for hypertriglyceridemia in Korean? 2. What are the relations with gene function or transcription? 3. Can an association analysis using two studies and mixed linear model reveal a novel allele associated with adult height? Consequently, I was investigated through imputation, association, and molecular modeling. Overall, my results suggested major effects on plasma TG levels may be exerted by the rs651821 and rs2075291, rs2075291 increases plasma TG level by causing structural changes in APOA5 and Nine significant SNPs were discovered to be associated with the adult height, and seven were identified for the first time. Finally, this study reveals a novel perspective of risk of Korean specific plasma TG level and suggests a determination of growth.
more목차
CHAPTER 1 Introduction
1.1 Genome-wide association study and Korean population
1.1.1 Genome-wide association study (GWAS)
1.1.2 The Korean genome and epidemiology study (KoGES)
1.2 Introduction of plasma triglyceride
1.3 A genome-wide association study of adult height
CHAPTER 2 Methods
2.1 Data source
2.2 Measurement of anthropometric and biochemical parameters
2.4 Statistical analysis in plasma triglyceride study
2.5 Statistical analysis in adult height study
2.6 Molecular dynamics simulations
2.7 MD simulations
CHAPTER 3 Association of BUD13-ZNF259-APOA5-APOA1-SIK3 cluster polymorphism in 11q23.3 and structure of APOA5 with increased plasma triglyceride levels in a Korean population
3.1 Summary
3.2 Plasma triglyceride associated with chromosome 11q23. 3
3.3 Structural modelling of polymorphic APOA 5
3.4 Distance and contact density between APOA5 monomers
3.5Different correlated movements between APOA5-WT and APOA5-MUT
3.6 Discussion
CHAPTER 4 A genome-wide association study of adult height using association analysis based on a mixed linear model in a Korean population
3.1 Summary
3.2 Association analysis for adult height using mixed-linear model
3.3 Discussion
CHAPTER 5 Bibliography
CHAPTER 6 Appendix
Paper 1
