title: Genome-wide association study identifies variants associated with histologic features of nonalcoholic Fatty liver disease.
abstract: OBJECTIVE
  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.
authors: Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA. nchalasa@iupui.edu
authors: Naga
authors: N
authors: Chalasani
authors: Xiuqing
authors: X
authors: Guo
authors: Rohit
authors: R
authors: Loomba
authors: Mark O
authors: MO
authors: Goodarzi
authors: Talin
authors: T
authors: Haritunians
authors: Soonil
authors: S
authors: Kwon
authors: Jinrui
authors: J
authors: Cui
authors: Kent D
authors: KD
authors: Taylor
authors: Laura
authors: L
authors: Wilson
authors: Oscar W
authors: OW
authors: Cummings
authors: Yii-Der Ida
authors: YD
authors: Chen
authors: Jerome I
authors: JI
authors: Rotter
mesh_terms: D004247:DNA / Q000235:genetics*; D018450:Disease Progression; D013186:Farnesyl-Diphosphate Farnesyltransferase / Q000235:genetics* / Q000378:metabolism; D005234:Fatty Liver / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study / Q000379:methods*; D005838:Genotype; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis
chemical_list: D004247:DNA; D013186:Farnesyl-Diphosphate Farnesyltransferase