title: Identification of FAM13A gene associated with the ratio of FEV1 to FVC in Korean population by genome-wide association studies including gene-environment interactions.
abstract: Chronic obstructive pulmonary disease (COPD) is a complex, multifactorial disease. Although smoking is a main risk factor for obstructive impairment, not all smokers develop this critical disease. We conducted a genome-wide association study to identify the association between genetic variants and pulmonary function and also examined how these variants relate to lung impairment in accordance with smoking behaviors. Using two community-based cohorts, the Ansan cohort (n=4319) and the Ansung cohort (n=3674), in the Korean Genome Epidemiology Study, we analyzed the association between genetic variants (single-nucleotide polymorphisms and haplotypes) and the ratio of FEV1 to FVC (FEV1/FVC) using multivariate linear regression models. Similar analyses were conducted after stratification by smoking status. Four genome-wide significant signals in the FAM13A gene (the strongest signal at rs2609264, P=1.76 × 10(-7) in a combined set) were associated with FEV1/FVC. For the association with ratio, the effect size in the CTGA haplotype (risk haplotype) was -0.57% (s.e., 0.11; P=2.10 × 10(-7)) as compared with the TCAG haplotype (reference haplotype) in a combined set. There was also a significant interaction of FAM13A haplotypes with heavy smoking on FEV1/FVC (P for interaction=0.028). We confirmed the previously reported association of FAM13A in 4q22.1 with pulmonary function. The FAM13A haplotypes also interacted with heavy smoking to affect the risk of reduced pulmonary function.
authors.affiliation: 1] Institute of Human Genomic Study, Ansan Hospital, Korea University, Ansan, Republic of Korea [2] Department of Public Health, Graduate School, Yonsei University, Seoul, Republic of Korea.
authors.forename: Soriul
authors.initials: S
authors.lastname: Kim
authors.affiliation: Institute of Human Genomic Study, Ansan Hospital, Korea University, Ansan, Republic of Korea.
authors.forename: Hyun
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Preventive Medicine, Ajou University School of Medicine, Suwon, Republic of Korea.
authors.forename: Namhan
authors.initials: N
authors.lastname: Cho
authors.affiliation: Institute of Human Genomic Study, Ansan Hospital, Korea University, Ansan, Republic of Korea.
authors.forename: Seung Ku
authors.initials: SK
authors.lastname: Lee
authors.affiliation: Center for Genome Science, National Institute of Health, Cheongwon, Republic of Korea.
authors.forename: Bok-Ghee
authors.initials: BG
authors.lastname: Han
authors.affiliation: Department of Bio-Medical Laboratory Science, College of Health Science, Eulji University, Sungnam, Republic of Korea.
authors.forename: Jae Woong
authors.initials: JW
authors.lastname: Sull
authors.affiliation: Department of Epidemiology and Health Promotion, Graduate School of Public Health, Yonsei University, Seoul, Republic of Korea.
authors.forename: Sun Ha
authors.initials: SH
authors.lastname: Jee
authors.affiliation: 1] Institute of Human Genomic Study, Ansan Hospital, Korea University, Ansan, Republic of Korea [2] Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Korea University Ansan Hospital, Ansan, Republic of Korea.
authors.forename: Chol
authors.initials: C
authors.lastname: Shin
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D015331:Cohort Studies; D005541:Forced Expiratory Volume / Q000502:physiology; D020690:GTPase-Activating Proteins / Q000235:genetics*; D005787:Gene Frequency; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods*; D006239:Haplotypes; D006801:Humans; D016014:Linear Models; D008875:Middle Aged; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide; D029424:Pulmonary Disease, Chronic Obstructive / Q000208:ethnology / Q000235:genetics* / Q000503:physiopathology; D056910:Republic of Korea / Q000453:epidemiology; D012307:Risk Factors; D012907:Smoking / Q000503:physiopathology; D014797:Vital Capacity / Q000502:physiology
chemical_list: C570078:FAM13A protein, human; D020690:GTPase-Activating Proteins