title: Genome-wide association study of serum albumin:globulin ratio in Korean populations.
abstract: Low albumin:globulin (A/G) ratios are associated with vascular adverse events, nephrotic syndrome and autoimmune disease. Genome-wide association studies (GWASs) have been identifying genetic variants associated with total serum protein, serum albumin and globulins, but A/G ratio has never been considered the target phenotype. To identify the genetic basis of the A/G ratio, we performed a GWAS on A/G ratio in 4205 individuals from the Ansan cohort and confirmed the results in 4637 subjects from the Ansung cohort. The single-nucleotide polymorphism (SNP) genotypes of Affymetrix SNP array 5.0 were obtained from the Korean Association Resource Consortium, and we selected 290 659 common SNPs with a minor allele frequency >0.05. Genetic factors for A/G ratio were analyzed by linear regression analysis, controlling for age, sex, body mass index, smoking status and alcohol drinking status as covariates. From the GWAS of the Ansan cohort, we identified two significant genome-wide signals (P-values<5 × 10(-8)) and 36 moderate signals (P-value<1.0 × 10(-4)). These 38 signals were tested in the Ansung population. Eleven SNPs from six loci (GALNT2, IRF4, HLA-DBP1, SLC31A1, FADS1 and TNFRSF13B) were replicated, with P-values<0.05. The most compelling association was observed in the TNFRSF13B locus on chromosome 17p11.2 (SNP: rs4561508), with an overall combined P-value=7.80 × 10(-24). The other significant signal was observed on chromosome 11q12.2-the FADS1 locus (SNP: rs174548)-with an overall combined P-value=3.54 × 10(-8).
authors.affiliation: Division of Epidemiology and Health Index, Center for Genome Science, Korea Centers for Disease Control and Prevention, Chungcheongbuk-do, Korea.
authors.forename: Kyung-Won
authors.initials: KW
authors.lastname: Hong
authors.forename: Hyun-Seok
authors.initials: HS
authors.lastname: Jin
authors.forename: Daesub
authors.initials: D
authors.lastname: Song
authors.forename: Hye-Kyoung
authors.initials: HK
authors.lastname: Kwak
authors.forename: Sung Soo
authors.initials: SS
authors.lastname: Kim
authors.forename: Yeonjung
authors.initials: Y
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D015331:Cohort Studies; D000090943:Delta-5 Fatty Acid Desaturase; D044943:Fatty Acid Desaturases / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D016014:Linear Models; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D056910:Republic of Korea; D012709:Serum Albumin / Q000032:analysis* / Q000235:genetics; D012712:Serum Globulins / Q000032:analysis* / Q000235:genetics; D053303:Transmembrane Activator and CAML Interactor Protein / Q000235:genetics
chemical_list: D000090943:Delta-5 Fatty Acid Desaturase; D012709:Serum Albumin; D012712:Serum Globulins; C108467:TNFRSF13B protein, human; D053303:Transmembrane Activator and CAML Interactor Protein; D044943:Fatty Acid Desaturases; C000716847:FADS1 protein, human