title: Linkage and association analysis of obesity traits reveals novel loci and interactions with dietary n-3 fatty acids in an Alaska Native (Yup'ik) population.
abstract: OBJECTIVE
  To identify novel genetic markers of obesity-related traits and to identify gene-diet interactions with n-3 polyunsaturated fatty acid (n-3 PUFA) intake in Yup'ik people.
  
  
  METHODS
  We measured body composition, plasma adipokines and ghrelin in 982 participants enrolled in the Center for Alaska Native Health Research (CANHR) Study. We conducted a genome-wide SNP linkage scan and targeted association analysis, fitting additional models to investigate putative gene-diet interactions. Finally, we performed bioinformatic analysis to uncover likely candidate genes within the identified linkage peaks.
  
  
  RESULTS
  We observed evidence of linkage for all obesity-related traits, replicating previous results and identifying novel regions of interest for adiponectin (10q26.13-2) and thigh circumference (8q21.11-13). Bioinformatic analysis revealed DOCK1, PTPRE (10q26.13-2) and FABP4 (8q21.11-13) as putative candidate genes in the newly identified regions. Targeted SNP analysis under the linkage peaks identified associations between three SNPs and obesity-related traits: rs1007750 on chromosome 8 and thigh circumference (P=0.0005), rs878953 on chromosome 5 and thigh skinfold (P=0.0004), and rs1596854 on chromosome 11 for waist circumference (P=0.0003). Finally, we showed that n-3 PUFA modified the association between obesity related traits and two additional variants (rs2048417 on chromosome 3 for adiponectin, P for interaction=0.0006 and rs730414 on chromosome 11 for percentage body fat, P for interaction=0.0004).
  
  
  CONCLUSIONS
  This study presents evidence of novel genomic regions and gene-diet interactions that may contribute to the pathophysiology of obesity-related traits among Yup'ik people.
authors.affiliation: Department of Biology, King University, 1350 King College Rd, Bristol, TN 37620, USA. Electronic address: lkvaughan@king.edu.
authors.forename: Laura Kelly
authors.initials: LK
authors.lastname: Vaughan
authors.affiliation: Department of Epidemiology, University of Alabama at Birmingham, 1665 University Blvd, Birmingham, AL 35294, USA. Electronic address: hwiener@uab.edu.
authors.forename: Howard W
authors.initials: HW
authors.lastname: Wiener
authors.affiliation: Department of Epidemiology, University of Alabama at Birmingham, 1665 University Blvd, Birmingham, AL 35294, USA. Electronic address: saslibek@uab.edu.
authors.forename: Stella
authors.initials: S
authors.lastname: Aslibekyan
authors.affiliation: Section on Statistical Genetics, Department of Biostatistics, University of Alabama at Birmingham, 1665 University Blvd, Birmingham, AL 35294, USA. Electronic address: dallison@uab.edu.
authors.forename: David B
authors.initials: DB
authors.lastname: Allison
authors.affiliation: Departments of Nutrition and Molecular Biosciences, University of California at Davis, 1 Shields Ave, Davis, CA 95616, USA. Electronic address: pjhavel@ucdavis.edu.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Havel
authors.affiliation: Departments of Nutrition and Molecular Biosciences, University of California at Davis, 1 Shields Ave, Davis, CA 95616, USA. Electronic address: klstanhope@ucdavis.edu.
authors.forename: Kimber L
authors.initials: KL
authors.lastname: Stanhope
authors.affiliation: USACenter for Alaska Native Health Research, Institute of Arctic Biology, 311 Irving I Building, University of Alaska Fairbanks, Fairbanks, AK 99775, USA. Electronic address: dmobrien@alaska.edu.
authors.forename: Diane M
authors.initials: DM
authors.lastname: O'Brien
authors.affiliation: USACenter for Alaska Native Health Research, Institute of Arctic Biology, 311 Irving I Building, University of Alaska Fairbanks, Fairbanks, AK 99775, USA. Electronic address: scarlett.hopkins@gmail.com.
authors.forename: Scarlett E
authors.initials: SE
authors.lastname: Hopkins
authors.affiliation: Department of Pediatrics, Section of Neonatology, University of Colorado Anschutz Medical Campus, 13123 East 16th Ave, Aurora, CO 80045, USA. Electronic address: dominick.lemas@ucdenver.edu.
authors.forename: Dominick J
authors.initials: DJ
authors.lastname: Lemas
authors.affiliation: USACenter for Alaska Native Health Research, Institute of Arctic Biology, 311 Irving I Building, University of Alaska Fairbanks, Fairbanks, AK 99775, USA. Electronic address: bboyer@alaska.edu.
authors.forename: Bert B
authors.initials: BB
authors.lastname: Boyer
authors.affiliation: Section on Statistical Genetics, Department of Biostatistics, University of Alabama at Birmingham, 1665 University Blvd, Birmingham, AL 35294, USA. Electronic address: htiwari@uab.edu.
authors.forename: Hemant K
authors.initials: HK
authors.lastname: Tiwari
mesh_terms: D000328:Adult; D000413:Alaska; D000886:Anthropometry; D001823:Body Composition / Q000235:genetics; D019295:Computational Biology; D003430:Cross-Sectional Studies; D004032:Diet; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D005260:Female; D008040:Genetic Linkage; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D004930:Inuit / Q000235:genetics*; D008297:Male; D009765:Obesity / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D055105:Waist Circumference / Q000235:genetics
chemical_list: D015525:Fatty Acids, Omega-3
keywords: Alaska Native; Linkage; Obesity; n-3 fatty acids