title: Admixture mapping of obesity-related traits in African Americans: the Atherosclerosis Risk in Communities (ARIC) Study.
abstract: Obesity is an important cause of morbidity and mortality worldwide. In the United States, the prevalence of obesity is higher in African Americans than whites, even after adjustment for socioeconomic status (SES). This leads to the hypothesis that differences in genetic background may contribute to racial/ethnic differences in obesity-related traits. We tested this hypothesis by conducting a genome-wide admixture mapping scan using 1,350 ancestry-informative single-nucleotide polymorphisms (SNPs) in 3,531 self-identified blacks from the Atherosclerosis Risk in Communities (ARIC) study. We used these markers to estimate the overall proportions of European ancestry (PEAs) for each individual and then scanned for the association between PEA and obesity-related traits (both continuous and dichotomous) at each locus. The median (interquartile range) PEA was 0.151 (0.115). PEA was inversely correlated with continuous BMI, weight, and subscapular skinfold thickness, even after adjusting for socioeconomic factors. In contrast, PEA was positively correlated with BMI-adjusted waist circumference. Using admixture mapping on dichotomized traits, we identified a locus on 2p23.3 to be suggestively associated with BMI (locus-specific lod = 4.11) and weight (locus-specific lod = 4.07). After adjusting for global PEA, each additional copy of a European ancestral allele at the 2p23.3 peak was associated with a BMI decrease of approximately 0.92 kg/m(2) (P = 2.9 x 10(-5)). Further mapping in this region on chromosome 2 may be able to uncover causative variants underlying obesity, which may offer insights into the control of energy homeostasis.
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
authors.forename: Ching-Yu
authors.initials: CY
authors.lastname: Cheng
authors.forename: David
authors.initials: D
authors.lastname: Reich
authors.forename: Josef
authors.initials: J
authors.lastname: Coresh
authors.forename: Eric
authors.initials: E
authors.lastname: Boerwinkle
authors.forename: Nick
authors.initials: N
authors.lastname: Patterson
authors.forename: Man
authors.initials: M
authors.lastname: Li
authors.forename: Kari E
authors.initials: KE
authors.lastname: North
authors.forename: Arti
authors.initials: A
authors.lastname: Tandon
authors.forename: Joan E
authors.initials: JE
authors.lastname: Bailey-Wilson
authors.forename: James G
authors.initials: JG
authors.lastname: Wilson
authors.forename: W H Linda
authors.initials: WH
authors.lastname: Kao
mesh_terms: D001741:Black or African American / Q000235:genetics*; D050197:Atherosclerosis; D001823:Body Composition / Q000235:genetics*; D015992:Body Mass Index; D001835:Body Weight / Q000235:genetics; D002874:Chromosome Mapping; D002889:Chromosomes, Human, Pair 2; D005260:Female; D005787:Gene Frequency; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000208:ethnology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012307:Risk Factors; D012885:Skinfold Thickness; D055105:Waist Circumference / Q000235:genetics; D044465:White People / Q000235:genetics
references.citation: Am J Epidemiol. 1989 Apr;129(4):687-702
references.pmid: 2646917
references.citation: Nat Genet. 2003 Apr;33(4):518-21
references.pmid: 12652300
references.citation: Am J Hum Genet. 1954 Mar;6(1):26-33
references.pmid: 13138567
references.citation: Epidemiol Rev. 2007;29:6-28
references.pmid: 17510091
references.citation: Am J Hum Genet. 2000 Feb;66(2):527-38
references.pmid: 10677313
references.citation: Metabolism. 1996 Sep;45(9):1119-24
references.pmid: 8781299
references.citation: Int J Obes Relat Metab Disord. 1995 Jul;19(7):449-57
references.pmid: 8520633
references.citation: Diabetes. 1999 Mar;48(3):643-4
references.pmid: 10078570
references.citation: Nature. 2007 Oct 18;449(7164):851-61
references.pmid: 17943122
references.citation: Proc Natl Acad Sci U S A. 1988 Dec;85(23):9119-23
references.pmid: 3194414
references.citation: Obes Res. 2003 Jul;11(7):904-11
references.pmid: 12855761
references.citation: Am J Hum Genet. 1997 Jan;60(1):188-96
references.pmid: 8981962
references.citation: Lancet. 1957 Nov 16;273(7003):959-66
references.pmid: 13482259
references.citation: Nat Genet. 2007 May;39(5):638-44
references.pmid: 17401364
references.citation: Cold Spring Harb Symp Quant Biol. 2003;68:69-78
references.pmid: 15338605
references.citation: Science. 1998 May 29;280(5368):1374-7
references.pmid: 9603720
references.citation: Osteoporos Int. 2007 Jun;18(6):733-41
references.pmid: 17235662
references.citation: Science. 2007 May 11;316(5826):889-94
references.pmid: 17434869
references.citation: Am J Hum Genet. 2008 Jan;82(1):81-7
references.pmid: 18179887
references.citation: Am J Hum Genet. 2004 May;74(5):979-1000
references.pmid: 15088269
references.citation: Diabetes. 2005 Aug;54(8):2492-6
references.pmid: 16046320
references.citation: Obes Res. 2005 Sep;13(9):1491-8
references.pmid: 16222047
references.citation: Am J Hum Genet. 2004 May;74(5):965-78
references.pmid: 15088268
references.citation: Nat Genet. 2008 Oct;40(10):1185-92
references.pmid: 18794854
references.citation: J Nutr. 1997 Sep;127(9):1887S-1890S
references.pmid: 9278576
references.citation: Nat Genet. 2005 Feb;37(2):177-81
references.pmid: 15665825
references.citation: JAMA. 2004 Jun 16;291(23):2847-50
references.pmid: 15199035
references.citation: Am J Hum Genet. 2007 Apr;80(4):716-26
references.pmid: 17357077
references.citation: Science. 2005 Feb 18;307(5712):1072-9
references.pmid: 15718463
references.citation: Nat Genet. 2005 Oct;37(10):1113-8
references.pmid: 16186815
references.citation: JAMA. 2006 Apr 5;295(13):1549-55
references.pmid: 16595758
references.citation: Ann Epidemiol. 2004 Aug;14(7):492-8
references.pmid: 15301786
references.citation: Am J Clin Nutr. 1995 Apr;61(4):765-71
references.pmid: 7702017
references.citation: Science. 1997 Nov 28;278(5343):1641-4
references.pmid: 9374468
references.citation: Nat Genet. 1997 Mar;15(3):273-6
references.pmid: 9054940
references.citation: Metabolism. 2003 Feb;52(2):186-91
references.pmid: 12601630
references.citation: Nat Genet. 1998 Nov;20(3):304-8
references.pmid: 9806554
references.citation: Am J Epidemiol. 1985 Jul;122(1):51-65
references.pmid: 4014201
references.citation: Hum Genet. 2006 Jul;119(6):624-33
references.pmid: 16738946
references.citation: PLoS Genet. 2006 Dec;2(12):e190
references.pmid: 17194218
references.citation: Obes Res. 2003 May;11(5):619-24
references.pmid: 12740451
references.citation: Proc Natl Acad Sci U S A. 2006 Sep 19;103(38):14068-73
references.pmid: 16945910
references.citation: Obesity (Silver Spring). 2008 Mar;16(3):600-7
references.pmid: 18239557
references.citation: Nat Genet. 2006 Aug;38(8):904-9
references.pmid: 16862161
references.citation: Hum Genet. 2007 Jun;121(5):565-75
references.pmid: 17356887
references.citation: Science. 1998 May 29;280(5368):1371-4
references.pmid: 9603719
references.citation: Am J Clin Nutr. 1982 Nov;36(5):936-42
references.pmid: 7137077
references.citation: Prev Med. 1979 Sep;8(5):525-37
references.pmid: 504076
references.citation: Am J Epidemiol. 1999 May 15;149(10):933-42
references.pmid: 10342802
references.citation: Am J Hum Genet. 2004 May;74(5):1001-13
references.pmid: 15088270
references.citation: PLoS Genet. 2007 Nov;3(11):e196
references.pmid: 18020707
references.citation: J Endocrinol. 2002 Mar;172(3):411-21
references.pmid: 11874690