title: Impact of obesity-related genes in Spanish population.
abstract: BACKGROUND
  The objective was to investigate the association between BMI and single nucleotide polymorphisms previously identified of obesity-related genes in two Spanish populations. Forty SNPs in 23 obesity-related genes were evaluated in a rural population characterized by a high prevalence of obesity (869 subjects, mean age 46 yr, 62% women, 36% obese) and in an urban population (1425 subjects, mean age 54 yr, 50% women, 19% obese). Genotyping was assessed by using SNPlex and PLINK for the association analysis.
  
  
  RESULTS
  Polymorphisms of the FTO were significantly associated with BMI, in the rural population (beta 0.87, p-value <0.001). None of the other SNPs showed significant association after Bonferroni correction in the two populations or in the pooled analysis. A weighted genetic risk score (wGRS) was constructed using the risk alleles of the Tag-SNPs with a positive Beta parameter in both populations. From the first to the fifth quintile of the score, the BMI increased 0.45 kg/m2 in Hortega and 2.0 kg/m2 in Pizarra. Overall, the obesity predictive value was low (less than 1%).
  
  
  CONCLUSIONS
  The risk associated with polymorphisms is low and the overall effect on BMI or obesity prediction is minimal. A weighted genetic risk score based on genes mainly acting through central nervous system mechanisms was associated with BMI but it yields minimal clinical prediction for the obesity risk in the general population.
authors.forename: Fernando
authors.initials: F
authors.lastname: Martínez-García
authors.forename: María L
authors.initials: ML
authors.lastname: Mansego
authors.forename: Gemma
authors.initials: G
authors.lastname: Rojo-Martínez
authors.forename: Griselda
authors.initials: G
authors.lastname: De Marco-Solar
authors.forename: Sonsoles
authors.initials: S
authors.lastname: Morcillo
authors.forename: Federico
authors.initials: F
authors.lastname: Soriguer
authors.affiliation: Hypertension Clinic, Hospital Clínico Universitario and INCLIVA, University of Valencia, Valencia 46010, Spain. josep.redon@uv.es.
authors.forename: Josep
authors.initials: J
authors.lastname: Redón
authors.forename: Monica
authors.initials: M
authors.lastname: Pineda Alonso
authors.forename: Juan C
authors.initials: JC
authors.lastname: Martín-Escudero
authors.forename: Richard S
authors.initials: RS
authors.lastname: Cooper
authors.forename: Felipe J
authors.initials: FJ
authors.lastname: Chaves
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D000067528:Ataxins; D015992:Body Mass Index; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics; D009765:Obesity / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics*; D013030:Spain; D044465:White People / Q000235:genetics*; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000067528:Ataxins; D015816:Cell Adhesion Molecules, Neuronal; D058851:GPI-Linked Proteins; C485559:NEGR1 protein, human; D009419:Nerve Tissue Proteins; D011506:Proteins; C518910:SH2B1 protein, human; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human