title: Common variants in LEPR, IL6, AMD1, and NAMPT do not associate with risk of juvenile and childhood obesity in Danes: a case-control study.
abstract: BACKGROUND
  Childhood obesity is a highly heritable disorder, for which the underlying genetic architecture is largely unknown. Four common variants involved in inflammatory-adipokine triggering (IL6 rs2069845, LEPR rs1137100, NAMPT rs3801266, and AMD1 rs2796749) have recently been associated with obesity and related traits in Indian children. The current study aimed to examine the effect of these variants on risk of childhood/juvenile onset obesity and on obesity-related quantitative traits in two Danish cohorts.
  
  
  METHODS
  Genotype information was obtained for 1461 young Caucasian men from the Genetics of Overweight Young Adults (GOYA) study (overweight/obese: 739 and normal weight: 722) and the Danish Childhood Obesity Biobank (TDCOB; overweight/obese: 1022 and normal weight: 650). Overweight/obesity was defined as having a body mass index (BMI) ≥25 kg/m(2); among children and youths, this cut-off was defined using age and sex-specific cut-offs corresponding to an adult body mass index ≥25 kg/m(2). Risk of obesity was assessed using a logistic regression model whereas obesity-related quantitative measures were analyzed using a general linear model (based on z-scores) stratifying on the case status and adjusting for age and gender. Meta-analyses were performed using the fixed effects model.
  
  
  RESULTS
  No statistically significant association with childhood/juvenile obesity was found for any of the four gene variants among the individual or combined analyses (rs2069845 OR: 0.94 CI: 0.85-1.04; rs1137100 OR: 1.01 CI: 0.90-1.14; rs3801266: 0.96 CI: 0.84-1.10; rs2796749 OR: 1.02 CI: 0.90-1.15; p > 0.05). However, among normal weight children and juvenile men, the LEPR rs1137100 A-allele significantly associated with lower BMI (β = -0.12, p = 0.0026).
  
  
  CONCLUSIONS
  The IL6, LEPR, NAMPT, and AMD1 gene variants previously found to associate among Indian children did not associate with risk of obesity or obesity-related quantitative measures among Caucasian children and juvenile men from Denmark.
authors.affiliation: The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, DIKU Building, Universitetsparken 1, 2100, Copenhagen, Denmark. mette.hollensted@sund.ku.dk.
authors.forename: Mette
authors.initials: M
authors.lastname: Hollensted
authors.affiliation: The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, DIKU Building, Universitetsparken 1, 2100, Copenhagen, Denmark. veertarun@gmail.com.|COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Ledreborg Allé 34, DK-2820, Copenhagen, Denmark. veertarun@gmail.com.|Steno Diabetes Center, Gentofte, Denmark. veertarun@gmail.com.
authors.forename: Tarunveer S
authors.initials: TS
authors.lastname: Ahluwalia
authors.affiliation: The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, DIKU Building, Universitetsparken 1, 2100, Copenhagen, Denmark. c.have@sund.ku.dk.
authors.forename: Christian Theil
authors.initials: CT
authors.lastname: Have
authors.affiliation: The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, DIKU Building, Universitetsparken 1, 2100, Copenhagen, Denmark. niels.grarup@sund.ku.dk.
authors.forename: Niels
authors.initials: N
authors.lastname: Grarup
authors.affiliation: The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, DIKU Building, Universitetsparken 1, 2100, Copenhagen, Denmark. crfo@regionsjaelland.dk.|The Children's Obesity Clinic, Department of Pediatrics, Copenhagen University Hospital Holbæk, Holbæk, Denmark. crfo@regionsjaelland.dk.
authors.forename: Cilius Esmann
authors.initials: CE
authors.lastname: Fonvig
authors.affiliation: The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, DIKU Building, Universitetsparken 1, 2100, Copenhagen, Denmark. ter@regionsjaelland.dk.|The Children's Obesity Clinic, Department of Pediatrics, Copenhagen University Hospital Holbæk, Holbæk, Denmark. ter@regionsjaelland.dk.
authors.forename: Tenna Ruest Haarmark
authors.initials: TR
authors.lastname: Nielsen
authors.affiliation: The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, DIKU Building, Universitetsparken 1, 2100, Copenhagen, Denmark. cats@regionsjaelland.dk.|The Children's Obesity Clinic, Department of Pediatrics, Copenhagen University Hospital Holbæk, Holbæk, Denmark. cats@regionsjaelland.dk.
authors.forename: Cæcilie
authors.initials: C
authors.lastname: Trier
authors.affiliation: MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, UK. l.paternoster@bristol.ac.uk.
authors.forename: Lavinia
authors.initials: L
authors.lastname: Paternoster
authors.affiliation: The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, DIKU Building, Universitetsparken 1, 2100, Copenhagen, Denmark. oluf@sund.ku.dk.
authors.forename: Oluf
authors.initials: O
authors.lastname: Pedersen
authors.affiliation: MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, UK. jhom@regionsjaelland.dk.
authors.forename: Jens-Christian
authors.initials: JC
authors.lastname: Holm
authors.affiliation: The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, DIKU Building, Universitetsparken 1, 2100, Copenhagen, Denmark. TSOE0005@regionh.dk.|MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, UK. TSOE0005@regionh.dk.|Institute of Preventive Medicine, Bispebjerg and Frederiksberg Hospital, The Capital Region, Copenhagen, Denmark. TSOE0005@regionh.dk.
authors.forename: Thorkild I A
authors.initials: TI
authors.lastname: Sørensen
authors.affiliation: The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, DIKU Building, Universitetsparken 1, 2100, Copenhagen, Denmark. torben.hansen@sund.ku.dk.
authors.forename: Torben
authors.initials: T
authors.lastname: Hansen
mesh_terms: D012437:Adenosylmethionine Decarboxylase / Q000235:genetics*; D015992:Body Mass Index; D016022:Case-Control Studies; D016207:Cytokines / Q000235:genetics*; D003718:Denmark; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D054409:Nicotinamide Phosphoribosyltransferase / Q000235:genetics*; D063766:Pediatric Obesity / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D054411:Receptors, Leptin / Q000235:genetics*; D055815:Young Adult
chemical_list: D016207:Cytokines; C508600:IL6 protein, human; D015850:Interleukin-6; C515448:LEPR protein, human; D054411:Receptors, Leptin; D054409:Nicotinamide Phosphoribosyltransferase; C085455:nicotinamide phosphoribosyltransferase, human; D012437:Adenosylmethionine Decarboxylase