title: A multianalytical approach to evaluate the association of 55 SNPs in 28 genes with obesity risk in North Indian adults.
abstract: OBJECTIVE
  The aim of the study was to investigate the association of 55 SNPs in 28 genes with obesity risk in a North Indian population using a multianalytical approach.
  
  
  METHODS
  Overall, 480 subjects from the North Indian population were studied using strict inclusion/exclusion criteria. SNP Genotyping was carried out by Sequenom Mass ARRAY platform (Sequenom, San Diego, CA) and validated Taqman®allelic discrimination (Applied Biosystems®). Statistical analyses were performed using SPSS software version 19.0, SNPStats, GMDR software (version 6) and GENEMANIA.
  
  
  RESULTS
  Logistic regression analysis of 55 SNPs revealed significant associations (P < .05) of 49 SNPs with BMI linked obesity risk whereas the remaining 6 SNPs revealed no association (P > .05). The pathway-wise G-score revealed the significant role (P = .0001) of food intake-energy expenditure pathway genes. In CART analysis, the combined genotypes of FTO rs9939609 and TCF7L2 rs7903146 revealed the highest risk for BMI linked obesity. The analysis of the FTO-IRX3 locus revealed high LD and high order gene-gene interactions for BMI linked obesity. The interaction network of all of the associated genes in the present study generated by GENEMANIA revealed direct and indirect connections. In addition, the analysis with centralized obesity revealed that none of the SNPs except for FTO rs17818902 were significantly associated (P < .05).
  
  
  CONCLUSIONS
  In this multi-analytical approach, FTO rs9939609 and IRX3 rs3751723, along with TCF7L2 rs7903146 and TMEM18 rs6548238, emerged as the major SNPs contributing to BMI linked obesity risk in the North Indian population.
authors.affiliation: Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Rae Bareli Road, Lucknow, Uttar Pradesh, 226014, India.
authors.forename: Apurva
authors.initials: A
authors.lastname: Srivastava
authors.affiliation: Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Rae Bareli Road, Lucknow, Uttar Pradesh, 226014, India.
authors.forename: Balraj
authors.initials: B
authors.lastname: Mittal
authors.affiliation: Department of Physiology, King George's Medical University, Chowk, Lucknow, Uttar Pradesh, 226003, India.
authors.forename: Jai
authors.initials: J
authors.lastname: Prakash
authors.affiliation: Darbhanga Medical College and Hospital Near Karpuri Chowk Benta Laheriasarai Darbhanga, Bihar, 846003, India.
authors.forename: Pranjal
authors.initials: P
authors.lastname: Srivastava
authors.affiliation: Sikkim Manipal Institute of Medical Sciences (SMIMS), National Highway 31A, Upper Tadong, Gangtok, 737102, Sikkim.
authors.forename: Nimisha
authors.initials: N
authors.lastname: Srivastava
authors.affiliation: Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Rae Bareli Road, Lucknow, Uttar Pradesh, 226014, India.
authors.forename: Neena
authors.initials: N
authors.lastname: Srivastava
mesh_terms: D000328:Adult; D005260:Female; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007194:India; D008297:Male; D009765:Obesity / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D055815:Young Adult
keywords: SNP; genetic association; genotype score; linkage disequilibrium; obesity