title: Genetic association and gene expression analysis identify FGFR1 as a new susceptibility gene for human obesity.
abstract: BACKGROUND
  Previous studies suggest a role for fibroblast growth factor receptor 1 (FGFR1) in the regulation of energy balance.
  
  
  OBJECTIVE
  Our objective was to investigate whether FGFR1 is an obesity gene by genetic association and functional studies.
  
  
  METHODS
  The study was designed to genotype common FGFR1 single-nucleotide polymorphisms (SNP) in large cohorts, confirm significant results in additional cohorts, and measure FGFR1 expression in human adipose tissue and in rodent hypothalamus.
  
  
  METHODS
  General community and referral centers for specialized care was the setting for the study.
  
  
  METHODS
  We genotyped FGFR1 SNP in 2438 obese and 2115 lean adults and 985 obese and 532 population-based children. Results were confirmed in 928 obese and 2738 population-based adults and 487 obese and 441 lean children. Abdominal sc adipose tissue was investigated in 202 subjects. We also investigated diet-induced, obese fasting, and fed rats.
  
  
  METHODS
  We analyzed the association between FGFR1 SNP and obesity. In secondary analyses, we related adipose FGFR1 expression to genotype, obesity, and degree of fat cell differentiation and related hypothalamic FGFR1 to energy balance.
  
  
  RESULTS
  FGFR1 rs7012413*T was nominally associated with obesity in all four cohorts; metaanalysis odds ratio = 1.17 (95% confidence interval = 1.10-1.25), and P = 1.8 × 10(-6), which was P = 7.0 × 10(-8) in the recessive model. rs7012413*T was associated with FGFR1 expression in adipose tissue (P < 0.0001). In this organ, but not in skeletal muscle, FGFR1 mRNA (P < 0.0001) and protein (P < 0.05) were increased in obesity. In rats, hypothalamic expression of FGFR1 declined after fasting (P < ]0.001) and increased after diet-induced obesity (P < 0.05).
  
  
  CONCLUSIONS
  FGFR1 is a novel obesity gene that may promote obesity by influencing adipose tissue and the hypothalamic control of appetite.
authors.affiliation: Department of Biosciences and Nutrition, Karolinska Institutet, SE-141 57 Stockholm, Sweden.
authors.forename: Hong
authors.initials: H
authors.lastname: Jiao
authors.forename: Peter
authors.initials: P
authors.lastname: Arner
authors.forename: Suzanne L
authors.initials: SL
authors.lastname: Dickson
authors.forename: Hubert
authors.initials: H
authors.lastname: Vidal
authors.forename: Niklas
authors.initials: N
authors.lastname: Mejhert
authors.forename: Corneliu
authors.initials: C
authors.lastname: Henegar
authors.forename: Magdalena
authors.initials: M
authors.lastname: Taube
authors.forename: Caroline
authors.initials: C
authors.lastname: Hansson
authors.forename: Anke
authors.initials: A
authors.lastname: Hinney
authors.forename: Pilar
authors.initials: P
authors.lastname: Galan
authors.forename: Chantal
authors.initials: C
authors.lastname: Simon
authors.forename: Angela
authors.initials: A
authors.lastname: Silveira
authors.forename: Anna
authors.initials: A
authors.lastname: Benrick
authors.forename: John-Olov
authors.initials: JO
authors.lastname: Jansson
authors.forename: Anne
authors.initials: A
authors.lastname: Bouloumié
authors.forename: Dominique
authors.initials: D
authors.lastname: Langin
authors.forename: Martine
authors.initials: M
authors.lastname: Laville
authors.forename: Cyrille
authors.initials: C
authors.lastname: Debard
authors.forename: Tomas
authors.initials: T
authors.lastname: Axelsson
authors.forename: Mikael
authors.initials: M
authors.lastname: Rydén
authors.forename: Juha
authors.initials: J
authors.lastname: Kere
authors.forename: Karin
authors.initials: K
authors.lastname: Dahlman-Wright
authors.forename: Anders
authors.initials: A
authors.lastname: Hamsten
authors.forename: Karine
authors.initials: K
authors.lastname: Clement
authors.forename: Ingrid
authors.initials: I
authors.lastname: Dahlman
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000818:Animals; D001066:Appetite / Q000235:genetics; D015153:Blotting, Western; D016009:Chi-Square Distribution; D002648:Child; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007031:Hypothalamus / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism*; D009765:Obesity / Q000235:genetics* / Q000378:metabolism; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D044465:White People
chemical_list: D012333:RNA, Messenger; C496348:FGFR1 protein, human; D051496:Receptor, Fibroblast Growth Factor, Type 1