title: Generalization of adiposity genetic loci to US Hispanic women.
abstract: BACKGROUND
  Obesity is a public health concern. Yet the identification of adiposity-related genetic variants among United States (US) Hispanics, which is the largest US minority group, remains largely unknown.
  
  
  OBJECTIVE
  To interrogate an a priori list of 47 (32 overall body mass and 15 central adiposity) index single-nucleotide polymorphisms (SNPs) previously studied in individuals of European descent among 3494 US Hispanic women in the Women's Health Initiative SNP Health Association Resource (WHI SHARe).
  
  
  METHODS
  Cross-sectional analysis of measured body mass index (BMI), waist circumference (WC) and waist-to-hip ratio (WHR) were inverse normally transformed after adjusting for age, smoking, center and global ancestry. WC and WHR models were also adjusted for BMI. Genotyping was performed using the Affymetrix 6.0 array. In the absence of an a priori selected SNP, a proxy was selected (r(2)0.8 in CEU).
  
  
  RESULTS
  Six BMI loci (TMEM18, NUDT3/HMGA1, FAIM2, FTO, MC4R and KCTD15) and two WC/WHR loci (VEGFA and ITPR2-SSPN) were nominally significant (P<0.05) at the index or proxy SNP in the corresponding BMI and WC/WHR models. To account for distinct linkage disequilibrium patterns in Hispanics and further assess generalization of genetic effects at each locus, we interrogated the evidence for association at the 47 surrounding loci within 1 Mb region of the index or proxy SNP. Three additional BMI loci (FANCL, TFAP2B and ETV5) and five WC/WHR loci (DNM3-PIGC, GRB14, ADAMTS9, LY86 and MSRA) displayed Bonferroni-corrected significant associations with BMI and WC/WHR. Conditional analyses of each index SNP (or its proxy) and the most significant SNP within the 1 Mb region supported the possible presence of index-independent signals at each of these eight loci as well as at KCTD15.
  
  
  CONCLUSIONS
  This study provides evidence for the generalization of nine BMI and seven central adiposity loci in Hispanic women. This study expands the current knowledge of common adiposity-related genetic loci to Hispanic women.
authors: Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors: M
authors: M
authors: Graff
authors: L
authors: L
authors: Fernández-Rhodes
authors: S
authors: S
authors: Liu
authors: C
authors: C
authors: Carlson
authors: S
authors: S
authors: Wassertheil-Smoller
authors: M
authors: M
authors: Neuhouser
authors: A
authors: A
authors: Reiner
authors: C
authors: C
authors: Kooperberg
authors: E
authors: E
authors: Rampersaud
authors: J E
authors: JE
authors: Manson
authors: L H
authors: LH
authors: Kuller
authors: B V
authors: BV
authors: Howard
authors: H M
authors: HM
authors: Ochs-Balcom
authors: K C
authors: KC
authors: Johnson
authors: M Z
authors: MZ
authors: Vitolins
authors: L
authors: L
authors: Sucheston
authors: K
authors: K
authors: Monda
authors: K E
authors: KE
authors: North
references: EMBO J. 1998 Feb 16;17(4):877-85
references: 9463366
references: Obesity (Silver Spring). 2012 Mar;20(3):622-7
references: 21701570
references: Nat Rev Genet. 2005 Apr;6(4):333-40
references: 15803201
references: Nat Genet. 2010 Nov;42(11):949-60
references: 20935629
references: Ann Epidemiol. 2003 Oct;13(9 Suppl):S18-77
references: 14575939
references: Nat Genet. 2012 Feb 19;44(3):307-11
references: 22344219
references: Nat Genet. 2009 Jan;41(1):25-34
references: 19079261
references: Hum Genet. 2009 Jun;125(5-6):615-26
references: 19322589
references: PLoS Genet. 2006 Dec;2(12):e190
references: 17194218
references: Nature. 2003 Dec 18;426(6968):789-96
references: 14685227
references: Hum Mol Genet. 2012 Mar 15;21(6):1419-32
references: 22131368
references: Nutr Diabetes. 2012 Sep 24;2:e47
references: 23168566
references: Lancet. 2004 Jan 10;363(9403):157-63
references: 14726171
references: Nat Genet. 2008 May;40(5):638-45
references: 18372903
references: Control Clin Trials. 1998 Feb;19(1):61-109
references: 9492970
references: Cardiovasc Diabetol. 2012 Jul 13;11:48
references: 22553958
references: Am J Clin Nutr. 2010 Apr;91(4):1020-6
references: 20164313
references: Public Health Nurs. 2009 Jan-Feb;26(1):23-38
references: 19154190
references: Nat Genet. 2010 Nov;42(11):937-48
references: 20935630
references: J Am Med Inform Assoc. 2012 Mar-Apr;19(2):289-94
references: 22319179
references: World Health Organ Tech Rep Ser. 1995;854:1-452
references: 8594834
references: Diabetes Care. 1991 Jul;14(7):628-38
references: 1914812
references: JAMA. 2012 Nov 7;308(17):1775-84
references: 23117778
references: Hum Mol Genet. 2010 Feb 1;19(3):545-52
references: 19880856
references: JAMA. 2006 Apr 5;295(13):1549-55
references: 16595758
references: PLoS Genet. 2013 Jun;9(6):e1003500
references: 23754948
references: PLoS Genet. 2009 Jun;5(6):e1000508
references: 19557161
references: Biochem J. 2005 Jun 1;388(Pt 2):393-406
references: 15901248
references: Int J Obes (Lond). 2012 Jan;36(1):61-8
references: 21986706
references: Int J Obes (Lond). 2012 Apr;36(4):542-7
references: 22083549
references: Nat Genet. 2013 Jun;45(6):690-6
references: 23583978
references: JAMA. 2012 Feb 1;307(5):491-7
references: 22253363
references: Free Radic Biol Med. 2013 Mar;56:123-32
references: 23089224
references: Nat Genet. 2012 Feb 19;44(3):302-6
references: 22344221
references: Genome Res. 2005 Nov;15(11):1592-3
references: 16251469
references: Mol Cell. 2005 Oct 28;20(2):325-33
references: 16246733
references: Mol Endocrinol. 2006 May;20(5):1104-11
references: 16373396
references: Am J Hum Genet. 2007 Sep;81(3):559-75
references: 17701901
references: Nat Genet. 2006 Aug;38(8):904-9
references: 16862161
references: Int J Mol Epidemiol Genet. 2011;2(2):138-44
references: 21686128
references: J Clin Endocrinol Metab. 2008 Jan;93(1):304-9
references: 17971425
references: Curr Opin Cell Biol. 2003 Feb;15(1):31-9
references: 12517701
references: NCHS Data Brief. 2010 Dec;(50):1-8
references: 21211165
references: Biochem Biophys Res Commun. 1996 Sep 4;226(1):193-9
references: 8806613
references: J Hum Genet. 2005;50(6):283-292
references: 15940393
references: PLoS One. 2009 Sep 30;4(9):e7236
references: 19789630
references: Nat Genet. 2009 Jan;41(1):18-24
references: 19079260
references: Nat Genet. 2011 Aug 28;43(10):984-9
references: 21874001