title: GWAS-Identified Common Variants With Nonalcoholic Fatty Liver Disease in Chinese Children.
abstract: OBJECTIVE
  Three genome-wide association studies were previously done for nonalcoholic fatty liver disease (NAFLD) among individuals of Western countries and identified several genetic variants associated with NAFLD. The study aimed to identify whether 7 GWAS-identified common variants (GCKR rs780094, PDGFA rs343064, FDFT1 rs2645424, COL13A1 rs1227756, EHBP1L1 rs6591182, NCAN rs2228603, and PNPLA3 rs738409) were associated with NAFLD in Chinese children.
  
  
  METHODS
  This case-control study recruited 1027 Chinese children of age 7 to 18 years, including 162 children with NAFLD and 865 children without NAFLD. Anthropometric measurements, alanine transaminase (ALT) detection, liver ultrasound examination, and genotyping of 7 variants were performed.
  
  
  RESULTS
  The G-allele of PNPLA3 rs738409 was associated with NAFLD (odds ratio [OR] 1.55, 95% confidence interval 1.13-2.11, P = 0.006) and moderate-to-severe steatosis (OR 3.77, 95% confidence interval 1.78-7.98, P = 0.001) adjusted for age, sex, and BMI standard deviation score. In addition, we found each G-allele of rs738409 increased ALT level by 1.09 IU/L (P = 0.011). Subjects carrying 10 or more risk alleles of 7 variants had an OR of 4.76 (P = 0.025) for NAFLD compared with subjects carrying 3 or fewer risk alleles.
  
  
  CONCLUSIONS
  The PNPLA3 rs738409 G-allele was associated with NAFLD and ALT level in Chinese children. It had stronger association with moderate-to-severe steatosis. Children carrying 10 or more risk alleles of 7 variants were susceptible for NAFLD.
authors.affiliation: Institute of Child and Adolescent Health, School of Public Health, Peking University, Beijing, China.
authors.forename: Xiao-Rui
authors.initials: XR
authors.lastname: Shang
authors.forename: Jie-Yun
authors.initials: JY
authors.lastname: Song
authors.forename: Fang-Hong
authors.initials: FH
authors.lastname: Liu
authors.forename: Jun
authors.initials: J
authors.lastname: Ma
authors.forename: Hai-Jun
authors.initials: HJ
authors.lastname: Wang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000293:Adolescent; D000410:Alanine Transaminase / Q000097:blood; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D002681:China; D011508:Chondroitin Sulfate Proteoglycans / Q000235:genetics; D024181:Collagen Type XIII / Q000235:genetics; D013186:Farnesyl-Diphosphate Farnesyltransferase / Q000235:genetics; D005260:Female; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D037181:Lectins, C-Type / Q000235:genetics; D008049:Lipase / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics; D058580:Neurocan; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood / Q000235:genetics*; D010982:Platelet-Derived Growth Factor / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000410:Alanine Transaminase; D011508:Chondroitin Sulfate Proteoglycans; D024181:Collagen Type XIII; D013186:Farnesyl-Diphosphate Farnesyltransferase; D037181:Lectins, C-Type; D008049:Lipase; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D058580:Neurocan; D010982:Platelet-Derived Growth Factor; C485100:GCKR protein, human; C075278:platelet-derived growth factor A; C076817:NCAN protein, human; C533682:PNPLA3 protein, human; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent