Admixture mapping of obesity-related traits in African Americans: the Atherosclerosis Risk in Communities (ARIC) Study.
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.
Cheng
Ching-Yu
CY
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
Reich
David
D
Coresh
Josef
J
Boerwinkle
Eric
E
Patterson
Nick
N
Li
Man
M
North
Kari E
KE
Tandon
Arti
A
Bailey-Wilson
Joan E
JE
Wilson
James G
JG
Kao
W H Linda
WH
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
Am J Epidemiol. 1989 Apr;129(4):687-702
2646917
Nat Genet. 2003 Apr;33(4):518-21
12652300
Am J Hum Genet. 1954 Mar;6(1):26-33
13138567
Epidemiol Rev. 2007;29:6-28
17510091
Am J Hum Genet. 2000 Feb;66(2):527-38
10677313
Metabolism. 1996 Sep;45(9):1119-24
8781299
Int J Obes Relat Metab Disord. 1995 Jul;19(7):449-57
8520633
Diabetes. 1999 Mar;48(3):643-4
10078570
Nature. 2007 Oct 18;449(7164):851-61
17943122
Proc Natl Acad Sci U S A. 1988 Dec;85(23):9119-23
3194414
Obes Res. 2003 Jul;11(7):904-11
12855761
Am J Hum Genet. 1997 Jan;60(1):188-96
8981962
Lancet. 1957 Nov 16;273(7003):959-66
13482259
Nat Genet. 2007 May;39(5):638-44
17401364
Cold Spring Harb Symp Quant Biol. 2003;68:69-78
15338605
Science. 1998 May 29;280(5368):1374-7
9603720
Osteoporos Int. 2007 Jun;18(6):733-41
17235662
Science. 2007 May 11;316(5826):889-94
17434869
Am J Hum Genet. 2008 Jan;82(1):81-7
18179887
Am J Hum Genet. 2004 May;74(5):979-1000
15088269
Diabetes. 2005 Aug;54(8):2492-6
16046320
Obes Res. 2005 Sep;13(9):1491-8
16222047
Am J Hum Genet. 2004 May;74(5):965-78
15088268
Nat Genet. 2008 Oct;40(10):1185-92
18794854
J Nutr. 1997 Sep;127(9):1887S-1890S
9278576
Nat Genet. 2005 Feb;37(2):177-81
15665825
JAMA. 2004 Jun 16;291(23):2847-50
15199035
Am J Hum Genet. 2007 Apr;80(4):716-26
17357077
Science. 2005 Feb 18;307(5712):1072-9
15718463
Nat Genet. 2005 Oct;37(10):1113-8
16186815
JAMA. 2006 Apr 5;295(13):1549-55
16595758
Ann Epidemiol. 2004 Aug;14(7):492-8
15301786
Am J Clin Nutr. 1995 Apr;61(4):765-71
7702017
Science. 1997 Nov 28;278(5343):1641-4
9374468
Nat Genet. 1997 Mar;15(3):273-6
9054940
Metabolism. 2003 Feb;52(2):186-91
12601630
Nat Genet. 1998 Nov;20(3):304-8
9806554
Am J Epidemiol. 1985 Jul;122(1):51-65
4014201
Hum Genet. 2006 Jul;119(6):624-33
16738946
PLoS Genet. 2006 Dec;2(12):e190
17194218
Obes Res. 2003 May;11(5):619-24
12740451
Proc Natl Acad Sci U S A. 2006 Sep 19;103(38):14068-73
16945910
Obesity (Silver Spring). 2008 Mar;16(3):600-7
18239557
Nat Genet. 2006 Aug;38(8):904-9
16862161
Hum Genet. 2007 Jun;121(5):565-75
17356887
Science. 1998 May 29;280(5368):1371-4
9603719
Am J Clin Nutr. 1982 Nov;36(5):936-42
7137077
Prev Med. 1979 Sep;8(5):525-37
504076
Am J Epidemiol. 1999 May 15;149(10):933-42
10342802
Am J Hum Genet. 2004 May;74(5):1001-13
15088270
PLoS Genet. 2007 Nov;3(11):e196
18020707
J Endocrinol. 2002 Mar;172(3):411-21
11874690