中国人群肝功能检测指标全基因组关联分析研究

肝功能检测(liver function test,LFTs)指标是受遗传和环境影响的复杂性状,具有个体差异性。为系统性研究中国人群全基因组范围内单核苷酸多态性(single nucleotide polymorphism,SNP)与肝功能指标之间的联系,本研究利用英国生物银行(UK Biobank)中1653名中国人的基因分型数据和表型数据为研究对象,利用PLINK软件进行全关联分析研究(genome-wide association study,GWAS),发现229个SNP与中国人群血液中的总胆红素(total bilirubin,TB)相关,27个SNP与中国人群血液中碱性磷酸酶(alkaline phosphatase,ALP)相关,36个SNP与中国人群血液中的γ-谷氨酰转肽酶(γ-glutamyl transpeptidase,GGT)相关,1个SNP与中国人群血液中的门冬氨酸氨基转移酶(aspartate transaminase,AST)相关,最显著的位点中有11个位点是新的LFTs关联位点。通过功能基因组分析,发现这些位点的临床意义(如吉尔伯特综合征),确定了候选基因(UGT1A,ABO,GGT1),为从遗传角度理解中国人群LFTs的个体差异性和肝功能指标临床精准检测提供了前期研究基础。

Genome-wide association study on liver function tests in Chinese

Liver function tests(LFTs)measure a series of complex traits that are affected by genetic and environmental factors.Previous studies demonstrated that there exist significant differences in LFTs across individuals,which may be the results of the unique genetic profile of each individual.Therefore,we performed a genome-wide association study(GWAS)to evaluate the influence of single nucleotide polymorphisms(SNPs)in LFTs and identify the significant association between genotypes and phenotypes using 1653 Chinese subjects from the UK Biobank database.We successfully identified 229 SNPs significantly associated with total bilirubin(TB)levels,27 SNPs significantly associated with alkaline phosphatase(ALP),and 36 SNPs significantly associated withγ-glutamyl transpeptidase(GGT)in serum.In addition,one SNP significantly associated with aspartate transaminase(AST)in serum was also found.Among the most significant ones,the topmost 11 SNPs were found to be associated with LFTs for the first time.Through functional genomic analysis,the clinical significance of these SNPs could be associated with diseases(e.g.Gilbert's syndrome)and the respective candidate genes(UGT1A,ABO,GGT1).This study provides a preliminary rationale for research to understand the associations of individual genetic differences and clinical liver functions in the Chinese population.