TY - JOUR
T1 - Genome-wide association study identifies variants associated with histologic features of nonalcoholic fatty liver disease
AU - Chalasani, Naga
AU - Guo, Xiuqing
AU - Loomba, Rohit
AU - Goodarzi, Mark O.
AU - Haritunians, Talin
AU - Kwon, Soonil
AU - Cui, Jinrui
AU - Taylor, Kent D.
AU - Wilson, Laura
AU - Cummings, Oscar W.
AU - Chen, Yii Der Ida
AU - Rotter, Jerome I.
PY - 2010/11
Y1 - 2010/11
N2 - Background & Aims: Little data are available from genome-wide association studies (GWASs) of liver histology in patients with nonalcoholic fatty liver disease (NAFLD). We conducted a pilot GWAS in patients with NAFLD, characterized by histology, who were enrolled in the NASH Clinical Research Network (CRN) Database Study. Methods: We studied clinical, laboratory, and histologic data from 236 non-Hispanic white women with NAFLD. We analyzed 324,623 single nucleotide polymorphisms (SNPs) from the 22 autosomal chromosomes. Multivariate-adjusted logistic regression analyses were conducted for binary outcomes, and linear regression analysis was applied for quantitative traits. A P value < 1 × 10-6 was considered to be significant. Results: In multivariate models adjusted for age, body mass index, diabetes, waist/hip ratios, and levels of glycated hemoglobin, the NAFLD activity score was associated with the SNP rs2645424 on chromosome 8 in farnesyl diphosphate farnesyl transferase 1 (FDFT1) (P = 6.8 × 10-7). The degree of fibrosis was associated with the SNP rs343062 on chromosome 7 (P = 2.7 × 10-8). SNPs associated with lobular inflammation included SNP rs1227756 on chromosome 10 in COL13A1 (P = 2.0 × 10 -7), rs6591182 on chromosome 11 (P = 8.6 × 10-7), and rs887304 on chromosome 12 in EFCAB4B (P = 7.7 × 10-7). SNPs associated with serum levels of alanine aminotransferase included rs2499604 on chromosome 1 (P = 2.2 × 10-6), rs6487679 on chromosome 12 in PZP (P = 1.3 × 10-6), rs1421201 on chromosome 18 (P = 1.0 × 10-5), and rs2710833 on chromosome 4 (P = 6.3 × 10 -7). No significant associations were observed between genotypes and steatosis, ballooning degeneration, portal inflammation, or other features of NAFLD. Conclusions: A GWAS significantly associated genetic variants with features of hepatic histology in patients with NAFLD. These findings should be validated in larger and more diverse cohorts.
AB - Background & Aims: Little data are available from genome-wide association studies (GWASs) of liver histology in patients with nonalcoholic fatty liver disease (NAFLD). We conducted a pilot GWAS in patients with NAFLD, characterized by histology, who were enrolled in the NASH Clinical Research Network (CRN) Database Study. Methods: We studied clinical, laboratory, and histologic data from 236 non-Hispanic white women with NAFLD. We analyzed 324,623 single nucleotide polymorphisms (SNPs) from the 22 autosomal chromosomes. Multivariate-adjusted logistic regression analyses were conducted for binary outcomes, and linear regression analysis was applied for quantitative traits. A P value < 1 × 10-6 was considered to be significant. Results: In multivariate models adjusted for age, body mass index, diabetes, waist/hip ratios, and levels of glycated hemoglobin, the NAFLD activity score was associated with the SNP rs2645424 on chromosome 8 in farnesyl diphosphate farnesyl transferase 1 (FDFT1) (P = 6.8 × 10-7). The degree of fibrosis was associated with the SNP rs343062 on chromosome 7 (P = 2.7 × 10-8). SNPs associated with lobular inflammation included SNP rs1227756 on chromosome 10 in COL13A1 (P = 2.0 × 10 -7), rs6591182 on chromosome 11 (P = 8.6 × 10-7), and rs887304 on chromosome 12 in EFCAB4B (P = 7.7 × 10-7). SNPs associated with serum levels of alanine aminotransferase included rs2499604 on chromosome 1 (P = 2.2 × 10-6), rs6487679 on chromosome 12 in PZP (P = 1.3 × 10-6), rs1421201 on chromosome 18 (P = 1.0 × 10-5), and rs2710833 on chromosome 4 (P = 6.3 × 10 -7). No significant associations were observed between genotypes and steatosis, ballooning degeneration, portal inflammation, or other features of NAFLD. Conclusions: A GWAS significantly associated genetic variants with features of hepatic histology in patients with NAFLD. These findings should be validated in larger and more diverse cohorts.
KW - Farnesyl Diphosphate Farnesyl Transferase 1
KW - GWAS
KW - NASH
KW - Nonalcoholic Steatohepatitis
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U2 - 10.1053/j.gastro.2010.07.057
DO - 10.1053/j.gastro.2010.07.057
M3 - Article
C2 - 20708005
AN - SCOPUS:78049457761
SN - 0016-5085
VL - 139
SP - 1567-1576.e6
JO - Gastroenterology
JF - Gastroenterology
IS - 5
ER -