title: Genetic Contribution of Variants near SORT1 and APOE on LDL Cholesterol Independent of Obesity in Children.
abstract: OBJECTIVE
  To assess potential effects of variants in six lipid modulating genes (SORT1, HMGCR, MLXIPL, FADS2, APOE and MAFB) on early development of dyslipidemia independent of the degree of obesity in children, we investigated their association with total (TC), low density lipoprotein (LDL-C), high density lipoprotein (HDL-C) cholesterol and triglyceride (TG) levels in 594 children. Furthermore, we evaluated the expression profile of the candidate genes during human adipocyte differentiation.
  
  
  RESULTS
  Expression of selected genes increased 10(1) to >10(4) fold during human adipocyte differentiation, suggesting a potential link with adipogenesis. In genetic association studies adjusted for age, BMI SDS and sex, we identified significant associations for rs599839 near SORT1 with TC and LDL-C and for rs4420638 near APOE with TC and LDL-C. We performed Bayesian modelling of the combined lipid phenotype of HDL-C, LDL-C and TG to identify potentially causal polygenic effects on this multi-dimensional phenotype and considering obesity, age and sex as a-priori modulating factors. This analysis confirmed that rs599839 and rs4420638 affect LDL-C.
  
  
  CONCLUSIONS
  We show that lipid modulating genes are dynamically regulated during adipogenesis and that variants near SORT1 and APOE influence lipid levels independent of obesity in children. Bayesian modelling suggests causal effects of these variants.
authors.affiliation: Center for Pediatric Research (CPL), University Hospital for Children and Adolescents Leipzig, Dept. of Women´s & Child Health, University of Leipzig, Leipzig, Germany.
authors.forename: Clara
authors.initials: C
authors.lastname: Breitling
authors.affiliation: Institute for Medical Informatics, Statistics and Epidemiology (IMISE), University of Leipzig, Leipzig, Germany; LIFE-Leipzig Research Center for Civilization Diseases, University of Leipzig, Leipzig, Germany.
authors.forename: Arnd
authors.initials: A
authors.lastname: Gross
authors.affiliation: Center for Pediatric Research (CPL), University Hospital for Children and Adolescents Leipzig, Dept. of Women´s & Child Health, University of Leipzig, Leipzig, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Büttner
authors.affiliation: Center for Pediatric Research (CPL), University Hospital for Children and Adolescents Leipzig, Dept. of Women´s & Child Health, University of Leipzig, Leipzig, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Weise
authors.affiliation: Integrated Research and Treatment Center Adiposity Diseases (IFB), Medical Faculty, University of Leipzig, Leipzig, Germany.
authors.forename: Dorit
authors.initials: D
authors.lastname: Schleinitz
authors.affiliation: Center for Pediatric Research (CPL), University Hospital for Children and Adolescents Leipzig, Dept. of Women´s & Child Health, University of Leipzig, Leipzig, Germany.
authors.forename: Wieland
authors.initials: W
authors.lastname: Kiess
authors.affiliation: Institute for Medical Informatics, Statistics and Epidemiology (IMISE), University of Leipzig, Leipzig, Germany; LIFE-Leipzig Research Center for Civilization Diseases, University of Leipzig, Leipzig, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Scholz
authors.affiliation: Integrated Research and Treatment Center Adiposity Diseases (IFB), Medical Faculty, University of Leipzig, Leipzig, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Kovacs
authors.affiliation: Center for Pediatric Research (CPL), University Hospital for Children and Adolescents Leipzig, Dept. of Women´s & Child Health, University of Leipzig, Leipzig, Germany; Integrated Research and Treatment Center Adiposity Diseases (IFB), Medical Faculty, University of Leipzig, Leipzig, Germany.
authors.forename: Antje
authors.initials: A
authors.lastname: Körner
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics*; D001499:Bayes Theorem; D002648:Child; D008078:Cholesterol, LDL / Q000097:blood*; D050171:Dyslipidemias / Q000097:blood* / Q000209:etiology* / Q000473:pathology; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D009765:Obesity / Q000097:blood / Q000150:complications* / Q000473:pathology; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D000099183:Sortilin
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D001057:Apolipoproteins E; D008078:Cholesterol, LDL; D000099183:Sortilin