title: SDCCAG8 obesity alleles and reduced weight loss after a lifestyle intervention in overweight children and adolescents.
abstract: Genome-wide association analyses (GWAS) contributed to the detection of a number of single-nucleotide polymorphisms (SNPs) associated with obesity. However, little is known about the impact of the obesity-risk alleles on weight loss-related phenotypes after lifestyle interventions. A recent meta-analysis of GWAS reported five genomic loci near or in the genes FTO, MC4R, TMEM18, SDCCAG8, TNKS/MSRA that were associated with obesity in children and adolescents. Here, we analyzed the effect of the 10 SNPs representative of the five loci on measures of weight loss and cardiometabolic risk after a 1-year lifestyle intervention in 401 children and adolescents (mean age 10.74 years; 55.4% female; mean BMI 27.42 kg/m(2), mean BMI-standard deviation score (SDS) 2.37). For confirmation of one locus genotyping of three intronic SNPs in SDCCAG8 was performed in 626 obese adults who completed the 10-week hypoenergetic diet program. Intronic variants of SDCCAG8, which are associated with early onset obesity, are associated with reduced weight loss after a 1-year lifestyle intervention in overweight children and adolescents even after adjusting for age, sex, baseline measurement, or multiple testing (all P < 10(-6)). However, our results could not be confirmed in 626 obese adults undertaking a hypoenergetic diet intervention.
authors.affiliation: Institute for Medical Informatics, Biometry and Epidemiology, University of Duisburg-Essen, Essen, Germany. andre.scherag@uk-essen.de
authors.forename: André
authors.initials: A
authors.lastname: Scherag
authors.forename: Michaela
authors.initials: M
authors.lastname: Kleber
authors.forename: Tanja
authors.initials: T
authors.lastname: Boes
authors.forename: Andreea-Liliana
authors.initials: AL
authors.lastname: Kolbe
authors.forename: Anne
authors.initials: A
authors.lastname: Ruth
authors.forename: Harald
authors.initials: H
authors.lastname: Grallert
authors.forename: Thomas
authors.initials: T
authors.lastname: Illig
authors.forename: Iris M
authors.initials: IM
authors.lastname: Heid
authors.forename: André M
authors.initials: AM
authors.lastname: Toschke
authors.forename: Katrine
authors.initials: K
authors.lastname: Grau
authors.forename: Thorkild I A
authors.initials: TI
authors.lastname: Sørensen
authors.forename: Johannes
authors.initials: J
authors.lastname: Hebebrand
authors.forename: Anke
authors.initials: A
authors.lastname: Hinney
authors.forename: Thomas
authors.initials: T
authors.lastname: Reinehr
mesh_terms: D000293:Adolescent; D000483:Alleles; D001324:Autoantigens / Q000235:genetics*; D015992:Body Mass Index; D002648:Child; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005858:Germany / Q000453:epidemiology; D006801:Humans; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics*; D009765:Obesity / Q000453:epidemiology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
chemical_list: D001324:Autoantigens; D009363:Neoplasm Proteins; C472380:SDCCAG8 protein, human