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천식의 새로운 유전인자 발굴을 위한 유전자 환경 상호작용 연구

Title
천식의 새로운 유전인자 발굴을 위한 유전자 환경 상호작용 연구
Other Titles
Gene environmental interaction study for discovery of new genetic factors for asthma
Author
차준호
Alternative Author(s)
Jun ho Cha
Advisor(s)
양철수
Issue Date
2021. 8
Publisher
한양대학교
Degree
Master
Abstract
Asthma is a representative complex disease caused by interaction of various environmental and immunological factors in addition to genetic factors. In this study, in order to investigate the gene-environmental interaction between Gene-smoke, and Gene-allergy in asthma, Health examines study (HEXA cohort) data of Korean Genome and Epidemiology Study (KoGES) were downloaded and Genome-wide association study (GWAS) was conducted by various statistical analysis techniques and models. In this study, Genome-wide association study (GWAS) was conducted, using Korean chips (KORV1.1) about a total of 58,434 adults (20,207 men, 38,227 women) over the age of 40. The analysis of general characteristics about subjects of study was conducted through chi-square test and t-test method, using R software. Gene-environmental interaction studies related to asthma were analyzed through logistic regression analysis using the PILNK software (v1.9). PLINK analysis was based on Missing genotype call ratio> 0.05, Minor Allele Frequency (MAF) <0.05, Hardy-Weinberg Equilibrium (HWE) p-value ≤ 10-5, and a total of 5,416,280 SNPs (Single Nucleotide Polymorphism) was used for analysis. In addition, MAGMA (Multi-marker Analysis of GenoMic Annotation) statistical technique was applied, and conducted using the FUMA program to study the association of Gene-level Gene-environment (smoke, allergy) interaction based on the SNP-level analysis result(p-value). As a result of performing SNP-level Gene-smoke interaction analysis, seven genes (LOC283038, SETDB1, KDM4C, ANXA9, CTXND2, FCRL3, TCTE3) were identified as candidate genes associated with asthma. In the Gene-allergy interaction study, six genes (CSMD1, RPH3AL, RIMBP2, IGF2BP1, CACNB2, TPTE2P6) were identified as candidate genes. In the Gene-level Gene-smoke interaction study, five genes (NTF3, SULT1C2, PRUNE, UCK1, IMPAD1) were identified as candidate genes associated with asthma, and in the Gene-allergy interaction study, a total of five candidate genes (GYPA, IGF2BP1, RNF187, COL4A2, DUOX1) were identified to be associated with asthma. Gene-level Gene-environment factor interaction analysis was performed using MAGMA (Multi-marker Analysis of GenoMic Annotation) statistical model. As a result, in the Gene-smoke interaction study, the NTF3, SULT1C2, PRUNE, UCK1 and IMPAD1 genes were identified, and in the Gene-allergy interaction study, the GYPA, IGF2BP1, RNF187, COL4A2 and DUOX1 genes were identified. This study is an association analysis study of Gene-environmental (smoke, allergy) interaction related to asthma, and it is significantly meaning that using Korean chips, a number of candidate genes related to asthma could be identified (containing previously reported candidate gene with asthma) and suggest a new candidate gene associated with asthma. In order to more clearly verify the Gene-environmental interaction associated with asthma, in the additional study, pathway analysis and replication studies using KOGES's Korea association resource (KARE cohort) data and Cardiovascular disease association study (CAVAS cohort) data are needed.|천식은 유전적 요인 외에도 환경적·면역학적 다양한 요인들이 함께 상호 작용하여 발생하는 대표적인 복합 질병이다. 본 연구에서는 천식과 흡연 및 알레르기의 유전자-환경 상호작용을 알아보기 위하여, 한국인유전체역학 조사사업(Korean Genome and Epidemiology Study, KoGES)의 도시 기반 코호트(Health examines study, HEXA cohort)자료를 분양 받아 여러 통계 분석 기법들을 활용하여 연관성 연구를 수행하였다. 본 연구에서는 40세 이상의 성인 총 58,434명(남자 20,207명, 여자 38,227명)를 대상으로 한국인 칩(KORV1.1)을 이용하여 유전체 데이터 분석을 진행하였다. 연구 대상자에 대한 일반적 특성 분석은 R software 를 사용하여 카이제곱 검정 및 t-test 검정을 통해 분석하였다. 천식과 연관된 유전자-환경 상호작용 연구는 PILNK(v1.9) 프로그램을 이용하여 로지스틱 회귀분석을 통해 분석하였다. PLINK 분석은 Missing genotype call ratio > 0.05, Minor Allele Frequency (MAF) < 0.05, Hardy-Weinberg Equilibrium (HWE) p-value ≤ 10-5 기준으로 하였고, 총 5,416,280 SNPs(Single Nucleotide Polymorphism, 단일염기다형성)가 분석에 사용되었다. 또한, SNP-level의 분석 결과(p-value)를 기반으로 Gene-level의 유전자-환경(흡연, 알레르기) 상호작용 연구를 FUMA 프로그램을 이용하여, MAGMA(Multi-marker Analysis of GenoMic Annotation) 통계 기법을 적용하였다. SNP-level 유전자-흡연 상호작용 분석을 수행한 결과, 천식과 연관된 후보 유전자로 7개의 유전자(LOC283038, SETDB1, KDM4C, ANXA9, CTXND2, FCRL3, TCTE3)을 확인하였다. 유전자-알레르기 상호작용 연구에선, 후보 유전자로 6개의 유전자(CSMD1, RPH3AL, RIMBP2, IGF2BP1, CACNB2, TPTE2P6)를 확인하였다. Gene-level 유전자-흡연 상호작용 연구에서는, 천식과 연관된 후보 유전자로 5개의 유전자(NTF3, SULT1C2, PRUNE, UCK1, IMPAD1)를 확인하였고, 유전자-알레르기 상호작용 연구에선, 총 5개의 후보 유전자(GYPA, IGF2BP1, RNF187, COL4A2, DUOX1)와 천식과의 연관성을 확인하였다. 본 연구는 천식과 연관된 유전자-환경(흡연, 알레르기) 상호작용 분석 연구로, 한국인 칩을 이용하여 천식과 연관된 후보 유전자들을 다수 발굴할 수 있었고, 기존에 보고된 유전자들 외에도 천식과 연관된 새로운 유전자를 제시할 수 있었음에 의의를 가진다. 앞으로 천식과 연관된 유전자-환경 상호작용을 보다 명확하게 검증하기 위해, 한국인유전체역학 조사 사업의 지역사회 기반 코호트(Korea association resource, KARE cohort)자료와 농촌 기반 코호트(Cardiovascular disease association study, CAVAS cohort)자료 등을 활용한 추가 연구가 필요할 것으로 생각된다.
URI
http://hanyang.dcollection.net/common/orgView/200000499129https://repository.hanyang.ac.kr/handle/20.500.11754/163992
Appears in Collections:
GRADUATE SCHOOL[S](대학원) > MOLECULAR & LIFE SCIENCE(분자생명과학과) > Theses (Master)
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