title: Evidence for novel genetic loci associated with metabolic traits in Yup'ik people.
abstract: OBJECTIVE
  To identify genomic regions associated with fasting plasma lipid profiles, insulin, glucose, and glycosylated hemoglobin in a Yup'ik study population, and to evaluate whether the observed associations between genetic factors and metabolic traits were modified by dietary intake of marine derived omega-3 polyunsaturated acids (n-3 PUFA).
  
  
  METHODS
  A genome-wide linkage scan was conducted among 982 participants of the Center for Alaska Native Health Research study. n-3 PUFA intake was estimated using the nitrogen stable isotope ratio (δ(15) N) of erythrocytes. All genotyped SNPs located within genomic regions with LOD scores > 2 were subsequently tested for individual SNP associations with metabolic traits using linear models that account for familial correlation as well as age, sex, community group, and n-3 PUFA intake. Separate linear models were fit to evaluate interactions between the genotype of interest and n-3 PUFA intake.
  
  
  RESULTS
  We identified several chromosomal regions linked to serum apolipoprotein A2, high density lipoprotein-, low density lipoprotein-, and total cholesterol, insulin, and glycosylated hemoglobin. Genetic variants found to be associated with total cholesterol mapped to a region containing previously validated lipid loci on chromosome 19, and additional novel peaks of biological interest were identified at 11q12.2-11q13.2. We did not observe any significant interactions between n-3 PUFA intake, genotypes, and metabolic traits.
  
  
  CONCLUSIONS
  We have completed a whole genome linkage scan for metabolic traits in Native Alaskans, confirming previously identified loci, and offering preliminary evidence of novel loci implicated in chronic disease pathogenesis in this population.
authors.affiliation: Department of Epidemiology, University of Alabama at Birmingham, Birmingham, Alabama, 35294.
authors.forename: Stella
authors.initials: S
authors.lastname: Aslibekyan
authors.forename: Laura Kelly
authors.initials: LK
authors.lastname: Vaughan
authors.forename: Howard W
authors.initials: HW
authors.lastname: Wiener
authors.forename: Dominick J
authors.initials: DJ
authors.lastname: Lemas
authors.forename: Yann C
authors.initials: YC
authors.lastname: Klimentidis
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Havel
authors.forename: Kimber L
authors.initials: KL
authors.lastname: Stanhope
authors.forename: Diane M
authors.initials: DM
authors.lastname: O'brien
authors.forename: Scarlett E
authors.initials: SE
authors.lastname: Hopkins
authors.forename: Bert B
authors.initials: BB
authors.lastname: Boyer
authors.forename: Hemant K
authors.initials: HK
authors.lastname: Tiwari
mesh_terms: D000328:Adult; D000413:Alaska; D001774:Blood Chemical Analysis; D015525:Fatty Acids, Omega-3 / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D005260:Female; D008040:Genetic Linkage; D055106:Genome-Wide Association Study; D006801:Humans; D016014:Linear Models; D008297:Male; D009587:Nitrogen Isotopes / Q000097:blood; D020641:Polymorphism, Single Nucleotide
chemical_list: D015525:Fatty Acids, Omega-3; D005231:Fatty Acids, Unsaturated; D009587:Nitrogen Isotopes
references.citation: Bioinformatics. 2010 Nov 1;26(21):2790-1
references.pmid: 20843958
references.citation: Hum Hered. 1992;42(1):16-27
references.pmid: 1555844
references.citation: Heredity (Edinb). 2005 Sep;95(3):221-7
references.pmid: 16077740
references.citation: BMC Syst Biol. 2011;5 Suppl 2:S13
references.pmid: 22784570
references.citation: Pharmacol Rep. 2007 Sep-Oct;59(5):483-99
references.pmid: 18048949
references.citation: PLoS Genet. 2009 Jan;5(1):e1000351
references.pmid: 19165344
references.citation: Am J Clin Nutr. 2009 Mar;89(3):913-9
references.pmid: 19176727
references.citation: Nucleic Acids Res. 2009 Jul;37(Web Server issue):W305-11
references.pmid: 19465376
references.citation: PLoS One. 2011 Mar 31;6(3):e18157
references.pmid: 21483817
references.citation: PLoS One. 2011;6(11):e27481
references.pmid: 22110658
references.citation: Obesity (Silver Spring). 2011 Sep;19(9):1840-6
references.pmid: 21527897
references.citation: Am J Hum Biol. 2006 Jul-Aug;18(4):525-31
references.pmid: 16788905
references.citation: Obesity (Silver Spring). 2007 Nov;15(11):2535-40
references.pmid: 18070741
references.citation: Int J Obes Relat Metab Disord. 2000 Feb;24(2):171-9
references.pmid: 10702767
references.citation: Curr Vasc Pharmacol. 2012 Mar;10(2):147-55
references.pmid: 22239624
references.citation: Am J Hum Genet. 1998 May;62(5):1198-211
references.pmid: 9545414
references.citation: Lipids Health Dis. 2011 Dec 31;10:248
references.pmid: 22208664
references.citation: Genet Epidemiol. 2005 Apr;28(3):193-206
references.pmid: 15637716
references.citation: Database (Oxford). 2011 Sep 18;2011:bar041
references.pmid: 21930507
references.citation: Trends Mol Med. 2003 Dec;9(12):549-57
references.pmid: 14659470
references.citation: Adv Genet. 2001;42:151-81
references.pmid: 11037320
references.citation: Int J Circumpolar Health. 2003 Dec;62(4):363-87
references.pmid: 14964764
references.citation: Genes Nutr. 2013 Sep;8(5):495-505
references.pmid: 23526194
references.citation: Genet Epidemiol. 1987;4(3):193-201
references.pmid: 3609719
references.citation: J Nutr. 2012 Jan;142(1):84-90
references.pmid: 22157543
references.citation: Nutr Metab Cardiovasc Dis. 2007 Feb;17(2):104-24
references.pmid: 17011759
references.citation: Nat Genet. 2002 Jan;30(1):97-101
references.pmid: 11731797
references.citation: J Mol Med (Berl). 1997 May;75(5):364-70
references.pmid: 9181478
references.citation: Clin Chem. 1999 Aug;45(8 Pt 1):1283-5
references.pmid: 10430797
references.citation: Ann Hum Genet. 2009 Sep;73(Pt 5):527-31
references.pmid: 19604226
references.citation: Science. 1996 Sep 13;273(5281):1516-7
references.pmid: 8801636
references.citation: Int J Circumpolar Health. 2010 Jun;69(3):236-52
references.pmid: 20501061
references.citation: Am J Hum Genet. 2004 Apr;74(4):765-9
references.pmid: 14997420
references.citation: Nat Genet. 2008 Feb;40(2):124-5
references.pmid: 18227866
references.citation: Nature. 2010 Aug 5;466(7307):707-13
references.pmid: 20686565
references.citation: Int J Circumpolar Health. 2007 Feb;66(1):8-18
references.pmid: 17451130
references.citation: Am J Hum Genet. 1998 Jul;63(1):259-66
references.pmid: 9634505
references.citation: Nucleic Acids Res. 2008 Jul 1;36(Web Server issue):W377-84
references.pmid: 18508807
references.citation: Br J Nutr. 2013 Mar 14;109(5):953-61
references.pmid: 23021345
references.citation: Nat Genet. 2006 Aug;38(8):904-9
references.pmid: 16862161
references.citation: Am J Hum Genet. 2008 Apr;82(4):949-58
references.pmid: 18371930
references.citation: J Lipid Res. 2012 Jan;53(1):175-84
references.pmid: 22045927
references.citation: Genetics. 2004 Dec;168(4):2349-61
references.pmid: 15371359