title: Multiple susceptibility loci at chromosome 11q23.3 are associated with plasma triglyceride in East Asians.
abstract: Genetic studies of plasma TG levels have identified associations with multiple candidate loci on chromosome11q23.3, which harbors a number of genes, including BUD13, ZNF259, and APOA5-A4-C3-A1. This study aimed to examine whether these multiple candidate genes on the 11q23.3 regions exert independent effects on TG levels or whether their effects are confounded by linkage disequilibrium (LD). We performed a genome-wide association study and consequent fine-mapping analyses on TG levels in two Korean population-based cohorts: the Korea Association Resource study (n = 8,223) and the Healthy Twin study (n = 1,735). A total of 301 loci reached genome-wide significance level in pooled analysis, including 10 SNPs with weak LD (r(2) < 0.06) clustered on 11q23.3: ApoA5 (rs651821, rs2075291); ZNF259 (rs964184, rs603446); BUD13 (rs11216126); Apoa4 (rs7396851); SIK3 (rs12292858); PCSK7 (rs199890178); PAFAH1B2 (rs12420127), and SIDT2 (rs2269399). When the inter-dependence between alleles was examined using conditional models, five loci on BUD13, ZNF259, and ApoA5 showed possible independent associations. A haplotype analysis using five SNPs revealed both hyper- and hypotriglyceridemic haplotypes, which are relatively common in Koreans (haplotype frequency 0.08-0.22). Our findings suggest the presence of multiple functional loci on 11q23.3, which might exert their effects on plasma TG level independently or through complex interactions between functional loci.
authors.affiliation: Institute of Health and Environment, Seoul National University, Seoul, Korea Genomic Medicine Institute (GMI), Medical Research Center, Seoul National University, Seoul, Korea.
authors.forename: Bayasgalan
authors.initials: B
authors.lastname: Gombojav
authors.affiliation: Complex Disease and Genome Epidemiology Branch, Department of Epidemiology, School of Public Health, Seoul National University, Seoul, Korea.
authors.forename: Soo Ji
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Complex Disease and Genome Epidemiology Branch, Department of Epidemiology, School of Public Health, Seoul National University, Seoul, Korea.
authors.forename: Minjung
authors.initials: M
authors.lastname: Kho
authors.affiliation: Department of Family Medicine, Samsung Medical Center and Center for Clinical Research, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Yun-Mi
authors.initials: YM
authors.lastname: Song
authors.affiliation: Department of Family Medicine, Busan Paik Hospital, Inje University College of Medicine, Busan, Korea.
authors.forename: Kayoung
authors.initials: K
authors.lastname: Lee
authors.affiliation: Institute of Health and Environment, Seoul National University, Seoul, Korea Complex Disease and Genome Epidemiology Branch, Department of Epidemiology, School of Public Health, Seoul National University, Seoul, Korea jsung@snu.ac.kr.
authors.forename: Joohon
authors.initials: J
authors.lastname: Sung
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000072040:Apolipoprotein A-V; D001054:Apolipoproteins A / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics*; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D004198:Disease Susceptibility; D005260:Female; D056726:Genetic Association Studies; D055106:Genome-Wide Association Study; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D026901:Membrane Transport Proteins; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D016601:RNA-Binding Proteins / Q000235:genetics*; D056910:Republic of Korea; D014280:Triglycerides / Q000097:blood / Q000235:genetics*
chemical_list: C437704:APOA5 protein, human; D000072040:Apolipoprotein A-V; D001054:Apolipoproteins A; C000595434:BUD13 homolog protein, human; D002352:Carrier Proteins; D026901:Membrane Transport Proteins; D016601:RNA-Binding Proteins; D014280:Triglycerides; C099746:ZPR1 protein, human
keywords: genetic epidemiology; genetic variant; genome-wide association study; polymorphisms