Mapping of hepatic expression quantitative trait loci (eQTLs) in a Han Chinese population

Abstract

BackgroundElucidating the genetic basis underlying hepatic gene expression variability is of importance to understand the aetiology of the disease and variation in drug metabolism. To date, no genome-wide expression quantitative trait loci (eQTLs) analysis has been conducted in the Han Chinese population, the largest ethnic group in the world.MethodsWe performed a genome-wide eQTL mapping in a set of Han Chinese liver tissue samples (n=64). The data were then compared with published eQTL data from a Caucasian population. We then performed correlations between these eQTLs with important pharmacogenes, and genome-wide association study (GWAS) identified single nucleotide polymorphisms (SNPs), in particular those identified in the Asian population.ResultsOur analyses identified 1669 significant eQTLs (false discovery rate (FDR) < 0.05). We found that 41% of Asian eQTLs were also eQTLs in Caucasians at the genome-wide significance level (p=10−8). Both cis- and trans-eQTLs in the Asian population were also more likely to be eQTLs in Caucasians (p<10−4). Enrichment analyses revealed that trait-associated GWAS-SNPs were enriched within the eQTLs identified in our data, so were the GWAS-SNPs specifically identified in Asian populations in a separate analysis (p<0.001 for both). We also found that hepatic expression of very important pharmacogenetic (VIP) genes (n=44) and a manually curated list of major genes involved in pharmacokinetics (n=341) were both more likely to be controlled by eQTLs (p<0.002 for both).ConclusionsOur study provided, for the first time, a comprehensive hepatic eQTL analysis in a non-European population, further generating valuable data for characterising the genetic basis of human diseases and pharmacogenetic traits.

Fatty acid desaturase 1 gene polymorphisms control human hepatic lipid composition

“…Given the nonsignificant association after Bonferroni correction for the locus‐wide eQTL mapping, we further validated the results in an additional hepatic eQTL data set published recently . Again, imputed and genotyped SNP data (k = 1,619 after QC) in the same region were used.…”

“…Given the nonsignificant association after Bonferroni correction for the locus-wide eQTL mapping, we further validated the results in an additional hepatic eQTL data set published recently. 22 Again, imputed and genotyped SNP data (k 5 1,619 after QC) in the same region were used. We found that, in this population, the SNPs in the LD block were strongly associated with the expression of FADS1 (10 28 < P < 10 26 ), but much more weakly with FADS2 (10 24 < P < 10 22 ), and no association with FADS3 (P > 0.05; Supporting Fig.…”

Association of patatin-like phospholipase domain-containing protein 3 gene polymorphisms with susceptibility of nonalcoholic fatty liver disease in a Han Chinese population

“…[21,22] Meanwhile, a healthy diet and regular exercise may enhance the insulin sensitivity and glucose homeostasis, thereby reducing the incidence of NAFLD. [23] Genetic factors have also been considered to play a very important role in the NAFLD development, and multiple GWAS have discovered several genes, including TM6SF2, SAMM50, PARVB, and PNPLA3, [13,15] which are potential candidates for NAFLD susceptibility and progression. Among these genes, a strong association has been demonstrated between PNPLA3 polymorphisms and NAFLD.…”

“…[15] As no study regarding the association of rs2896019 and rs3810622 and predisposition to NAFLD in other populations has yet been published, in this study, we will further evaluate the association of rs2896019 and rs3810622 polymorphisms in PNPLA3 gene with NAFLD based on a Han Chinese population, which represents the world's largest population, to further elucidate the genetic causes of NAFLD.…”

Discovery of novel hepatocyte eQTLs in African Americans

“…Liver is a critical organ for understanding drug metabolism, as well as coagulopathies and metabolic disorders, and is likely to be the causal tissue for many GWAS studies [12][13][14]. However, eQTL mapping in liver tissue has been primarily conducted in European and Asian populations [9,15,16]. Due to the difficulty in obtaining liver from African American (AA) donors, there are no studies performed exclusively in the liver of AAs, leaving the genome-wide regulation of gene expression in populations with high levels of African ancestry unexplored.…”