10.6084/m9.figshare.5124418.v1 Gorden A. Gorden A. Yang R. Yang R. Yerges-Armstrong L.M. Yerges-Armstrong L.M. Ryan K.A. Ryan K.A. Speliotes E. Speliotes E. Borecki I.B. Borecki I.B. Harris T.B. Harris T.B. Chu X. Chu X. Wood G.C. Wood G.C. Still C.D. Still C.D. Supplementary Material for: Genetic Variation at NCAN Locus Is Associated with Inflammation and Fibrosis in Non-Alcoholic Fatty Liver Disease in Morbid Obesity Karger Publishers 2013 Obesity Dyslipidemia Steatohepatitis Cirrhosis Steatosis 2013-04-10 00:00:00 Dataset https://karger.figshare.com/articles/dataset/Supplementary_Material_for_Genetic_Variation_at_NCAN_Locus_Is_Associated_with_Inflammation_and_Fibrosis_in_Non-Alcoholic_Fatty_Liver_Disease_in_Morbid_Obesity/5124418 <b><i>Objective:</i></b> Obesity-associated non-alcoholic fatty liver disease (NAFLD) may cause liver dysfunction and failure. In a previously reported genome-wide association meta-analysis, single nucleotide polymorphisms (SNPs) near <i>PNPLA3</i>, <i>NCAN</i>, <i>GCKR</i>, <i>LYPLAL1</i> and <i>PPP1R3B</i> were associated with NAFLD and with distinctive serum lipid profiles. The present study examined the relevance of these variants to NAFLD in extreme obesity. <b><i>Methods:</i></b> In 1,092 bariatric surgery patients, the candidate SNPs were genotyped and association analyses with liver histology and serum lipids were performed. <b><i>Results:</i></b> We replicated the association of hepatosteatosis with <i>PNPLA3</i> rs738409[G] and with <i>NCAN</i> rs2228603[T]. We also replicated the association of rs2228603[T] with hepatic inflammation and fibrosis. rs2228603[T] was associated with lower serum low-density lipoprotein, total cholesterol and triglycerides. After stratification by the presence or absence of NAFLD, these associations were present predominantly in the subgroup with NAFLD. <b><i>Conclusion:</i></b><i>NCAN</i> rs2228603[T] is a risk factor for liver inflammation and fibrosis, suggesting that this locus is responsible for progression from steatosis to steatohepatitis. In this bariatric cohort, rs2228603[T] was associated with low serum lipids only in patients with NAFLD. This supports a NAFLD model in which the liver may sequester triglycerides as a result of either increased triglyceride uptake and/or decreased lipolysis.