Division of Epidemiology and Health Index, Center for Genome Science, Korea Centers for Disease Control and Prevention, Chungcheongbuk-do, Korea.
J Hum Genet. 2013 Mar;58(3):174-7. doi: 10.1038/jhg.2012.130. Epub 2013 Jan 10.
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).
低白蛋白与球蛋白 (A/G) 比值与血管不良事件、肾病综合征和自身免疫性疾病有关。全基因组关联研究 (GWAS) 一直在鉴定与总血清蛋白、血清白蛋白和球蛋白相关的遗传变异，但 A/G 比值从未被视为目标表型。为了确定 A/G 比值的遗传基础，我们对来自 Ansan 队列的 4205 名个体的 A/G 比值进行了 GWAS，并在来自 Ansung 队列的 4637 名个体中证实了结果。Affymetrix SNP 阵列 5.0 的单核苷酸多态性 (SNP) 基因型从韩国协会资源联合会获得，我们选择了 290659 个具有 >0.05 次要等位基因频率的常见 SNP。A/G 比值的遗传因素通过线性回归分析进行分析，控制年龄、性别、体重指数、吸烟状态和饮酒状态作为协变量。从 Ansan 队列的 GWAS 中，我们确定了两个显著的全基因组信号（P 值<5×10(-8))和 36 个中度信号（P 值<1.0×10(-4))。这些 38 个信号在 Ansung 人群中进行了测试。六个基因座（GALNT2、IRF4、HLA-DBP1、SLC31A1、FADS1 和 TNFRSF13B）的 11 个 SNP 得到了复制，P 值<0.05。最引人注目的关联发生在 17p11.2 染色体上的 TNFRSF13B 基因座（SNP：rs4561508），总合并 P 值=7.80×10(-24)。另一个显著的信号发生在 11q12.2 染色体上的 FADS1 基因座（SNP：rs174548），总合并 P 值=3.54×10(-8)。
