title: Determination of obesity associated gene variants related to TMEM18 through ultra-deep targeted re-sequencing in a case-control cohort for pediatric obesity.
abstract: Genome-wide association studies (GWAS) have revealed association of a locus approximately 25b downstream of the TMEM18 gene with body mass and obesity. We utilized targeted re-sequencing of the body mass associated locus in proximity of TMEM18 in a case-control population of severely obese children and adolescents from the Stockholm area. We expanded our study to include the TMEM18 gene itself, with the aim of identifying body mass associated genetic variants. Sequencing was performed on the SOLiD platform, on long-range PCR fragments generated through targeted amplification of the regions of interest. Candidate single nucleotide polymorphisms (SNPs) were validated by TaqMan genotyping. We were able to observe 131 SNPs across the re-sequenced regions. Chi squared tests comparing the allele frequencies between cases and controls revealed 57 SNPs as candidates for association with obesity. Validation and replication genotyping revealed robust associations for SNPs within the haplotype block region located downstream from the TMEM18 gene. This study provides a high resolution map of the genetic variation pattern in the TMEM18 gene, as well as the associated haplotype block, and further strengthens the association of variants within the proximal haplotype block with obesity and body mass.
authors.affiliation: Department of Neuroscience,Functional Pharmacology,Uppsala University,BMC,Uppsala,Sweden.
authors.forename: Mathias
authors.initials: M
authors.lastname: Rask-Andersen
authors.affiliation: Department of Neuroscience,Functional Pharmacology,Uppsala University,BMC,Uppsala,Sweden.
authors.forename: Markus
authors.initials: M
authors.lastname: Sällman Almén
authors.affiliation: Department of Neuroscience,Functional Pharmacology,Uppsala University,BMC,Uppsala,Sweden.
authors.forename: Josefin A
authors.initials: JA
authors.lastname: Jacobsson
authors.affiliation: Department of Immunology,Genetics, and Pathology,SciLifeLab Uppsala,Rudbeck Laboratory,Uppsala University,Uppsala,Sweden.
authors.forename: Adam
authors.initials: A
authors.lastname: Ameur
authors.affiliation: Department of Nutrition and Dietetics,Harokopio University of Athens,Athens,Greece.
authors.forename: George
authors.initials: G
authors.lastname: Moschonis
authors.affiliation: Department of Nutrition and Dietetics,Harokopio University of Athens,Athens,Greece.
authors.forename: George
authors.initials: G
authors.lastname: Dedoussis
authors.affiliation: Department for Clinical Science,Intervention and Technology,Karolinska Institutet,Division of Pediatrics,National Childhood Obesity Centre,Stockholm,Sweden.
authors.forename: Claude
authors.initials: C
authors.lastname: Marcus
authors.affiliation: Department of Immunology,Genetics, and Pathology,SciLifeLab Uppsala,Rudbeck Laboratory,Uppsala University,Uppsala,Sweden.
authors.forename: Ulf
authors.initials: U
authors.lastname: Gyllensten
authors.affiliation: Department of Neuroscience,Functional Pharmacology,Uppsala University,BMC,Uppsala,Sweden.
authors.forename: Robert
authors.initials: R
authors.lastname: Fredriksson
authors.affiliation: Department of Neuroscience,Functional Pharmacology,Uppsala University,BMC,Uppsala,Sweden.
authors.forename: Helgi B
authors.initials: HB
authors.lastname: Schiöth
mesh_terms: D000293:Adolescent; D016022:Case-Control Studies; D002648:Child; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D060005:Genotyping Techniques / Q000379:methods; D006239:Haplotypes; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D063766:Pediatric Obesity / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
chemical_list: D008565:Membrane Proteins; C530715:TMEM18 protein, human