title: Genetic association analysis of 30 genes related to obesity in a European American population.
abstract: OBJECTIVE
  Obesity, which is frequently associated with diabetes, hypertension and cardiovascular diseases, is primarily the result of a net excess of caloric intake over energy expenditure. Human obesity is highly heritable, but the specific genes mediating susceptibility in non-syndromic obesity remain unclear. We tested candidate genes in pathways related to food intake and energy expenditure for association with body mass index (BMI).
  
  
  METHODS
  We reanalyzed 355 common genetic variants of 30 candidate genes in seven molecular pathways related to obesity in 1982 unrelated European Americans from the New York Cancer Project. Data were analyzed by using a Bayesian hierarchical generalized linear model. The BMIs were log-transformed and then adjusted for covariates, including age, age(2), gender and diabetes status. The single-nucleotide polymorphisms (SNPs) were modeled as additive effects.
  
  
  RESULTS
  With the stipulated adjustments, nine SNPs in eight genes were significantly associated with BMI: ghrelin (GHRL; rs35683), agouti-related peptide (AGRP; rs5030980), carboxypeptidase E (CPE; rs1946816 and rs4481204), glucagon-like peptide-1 receptor (GLP1R; rs2268641), serotonin receptors (HTR2A; rs912127), neuropeptide Y receptor (NPY5R;Y5R1c52), suppressor of cytokine signaling 3 (SOCS3; rs4969170) and signal transducer and activator of transcription 3 (STAT3; rs4796793). We also found a gender-by-SNP interaction (rs1745837 in HTR2A), which indicated that variants in the gene HTR2A had a stronger association with BMI in males. In addition, NPY1R was detected as having a significant gene effect even though none of the SNPs in this gene was significant.
  
  
  CONCLUSIONS
  Variations in genes AGRP, CPE, GHRL, GLP1R, HTR2A, NPY1R, NPY5R, SOCS3 and STAT3 showed modest associations with BMI in European Americans. The pathways in which these genes participate regulate energy intake, and thus these associations are mechanistically plausible in this context.
authors.affiliation: Department of Biostatistics, School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: P
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of Biostatistics, School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: H K
authors.initials: HK
authors.lastname: Tiwari
authors.affiliation: Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.
authors.forename: W-Y
authors.initials: WY
authors.lastname: Lin
authors.affiliation: Nutrition Obesity Research Center, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: D B
authors.initials: DB
authors.lastname: Allison
authors.affiliation: 1] Columbia University Medical Center, New York, NY, USA [2] Naomi Berrie Diabetes Center, New York, NY, USA.
authors.forename: W K
authors.initials: WK
authors.lastname: Chung
authors.affiliation: 1] Columbia University Medical Center, New York, NY, USA [2] Naomi Berrie Diabetes Center, New York, NY, USA.
authors.forename: R L
authors.initials: RL
authors.lastname: Leibel
authors.affiliation: Department of Biostatistics, School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: N
authors.initials: N
authors.lastname: Yi
authors.affiliation: Department of Biostatistics, School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: N
authors.initials: N
authors.lastname: Liu
mesh_terms: D000328:Adult; D054369:Agouti-Related Protein; D001823:Body Composition / Q000235:genetics*; D015992:Body Mass Index; D002227:Carbazoles; D004435:Eating / Q000235:genetics; D004734:Energy Metabolism / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics*; D054439:Ghrelin; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D008297:Male; D009025:Morpholines; D009518:New York / Q000453:epidemiology; D009765:Obesity / Q000453:epidemiology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D018027:Receptors, Glucagon; D017476:Receptors, Neuropeptide Y; D050796:STAT3 Transcription Factor; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D014481:United States / Q000453:epidemiology; D044465:White People / Q000235:genetics*
chemical_list: C515198:AGRP protein, human; D054369:Agouti-Related Protein; D002227:Carbazoles; C515349:GHRL protein, human; C000593833:GLP1R protein, human; D054439:Ghrelin; D000067757:Glucagon-Like Peptide-1 Receptor; D009025:Morpholines; C463522:NPY5RA 972; D018027:Receptors, Glucagon; D017476:Receptors, Neuropeptide Y; C106644:SOCS3 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; C097212:neuropeptide Y-Y1 receptor
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