Discerning the ancestry of European Americans in genetic association studies

被引：237

作者：

Price, Alkes L. ^{[1
,2
,3
]}

Butler, Johannah ^{[2
,3
,4
,5
,6
]}

Patterson, Nick ^{[2
,3
]}

Capelli, Cristian ^{[7
]}

Pascali, Vincenzo L. ^{[8
]}

Scarnicci, Francesca ^{[8
]}

Ruiz-Linares, Andres ^{[9
]}

Groop, Leif ^{[10
]}

Saetta, Angelica A. ^{[11
]}

Korkolopoulou, Penelope ^{[11
]}

Seligsohn, Uri ^{[13
]}

Waliszewska, Alicja ^{[2
,3
]}

Schirmer, Christine ^{[2
,3
]}

Ardlie, Kristin ^{[2
,3
]}

Ramos, Alexis ^{[2
,3
,4
,5
,6
]}

Nemesh, James ^{[2
,3
,4
,5
,6
]}

Arbeitman, Lori ^{[2
,3
,4
,5
,6
]}

Goldstein, David B. ^{[12
]}

Reich, David ^{[1
,2
,3
]}

Hirschhorn, Joel N. ^{[1
,2
,3
,4
,5
,6
]}

机构：

[1] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA

[2] Broad Inst Harvard, Program Med & Populat Genet, Cambridge, MA USA

[3] MIT, Cambridge, MA 02139 USA

[4] Childrens Hosp, Program Genom, Boston, MA 02115 USA

[5] Childrens Hosp, Div Genet, Boston, MA 02115 USA

[6] Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA

[7] Univ Oxford, Dept Zool, Oxford OX1 3PS, England

[8] Univ Cattolica Sacro Cuore, Ist Med Legale, Forens Genet Lab, Rome, Italy

[9] UCL, Dept Biol, Galton Lab, London WC1E 6BT, England

[10] Malmo Univ Hosp, Univ Lund, Dept Clin Sci Diabet & Endocrinol, Malmo, Sweden

[11] Univ Athens, Sch Med, Dept Pathol, Athens 11528, Greece

[12] Duke Univ, Ctr Populat & Pharmarcogenet, Inst Genome Sci & Policy, Durham, NC USA

[13] Chaim Sheba Med Ctr, Amalia Biron Inst Thrombosis & Hemostasis, IL-52621 Tel Hashomer, Israel

来源：

PLOS GENETICS | 2008年 / 4卷 / 01期

关键词：

D O I：

10.1371/journal.pgen.0030236

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

European Americans are often treated as a homogeneous group, but in fact form a structured population due to historical immigration of diverse source populations. Discerning the ancestry of European Americans genotyped in association studies is important in order to prevent false-positive or false-negative associations due to population stratification and to identify genetic variants whose contribution to disease risk differs across European ancestries. Here, we investigate empirical patterns of population structure in European Americans, analyzing 4,198 samples from four genome-wide association studies to show that components roughly corresponding to northwest European, southeast European, and Ashkenazi Jewish ancestry are the main sources of European American population structure. Building on this insight, we constructed a panel of 300 validated markers that are highly informative for distinguishing these ancestries. We demonstrate that this panel of markers can be used to correct for stratification in association studies that do not generate dense genotype data.

引用

页码：0009 / 0017

页数：9

共 37 条

[1] A haplotype map of the human genome [J].

Altshuler, D ;

Brooks, LD ;

Chakravarti, A ;

Collins, FS ;

Daly, MJ ;

Donnelly, P ;

Gibbs, RA ;

Belmont, JW ;

Boudreau, A ;

Leal, SM ;

Hardenbol, P ;

Pasternak, S ;

Wheeler, DA ;

Willis, TD ;

Yu, FL ;

Yang, HM ;

Zeng, CQ ;

Gao, Y ;

Hu, HR ;

Hu, WT ;

Li, CH ;

Lin, W ;

Liu, SQ ;

Pan, H ;

Tang, XL ;

Wang, J ;

Wang, W ;

Yu, J ;

Zhang, B ;

Zhang, QR ;

Zhao, HB ;

Zhao, H ;

Zhou, J ;

Gabriel, SB ;

Barry, R ;

Blumenstiel, B ;

Camargo, A ;

Defelice, M ;

Faggart, M ;

Goyette, M ;

Gupta, S ;

Moore, J ;

Nguyen, H ;

Onofrio, RC ;

Parkin, M ;

Roy, J ;

Stahl, E ;

Winchester, E ;

Ziaugra, L ;

Shen, Y .

NATURE, 2005, 437 (7063) :1299-1320

[2] The common PPARγ Pro12Ala polymorphism is associated with decreased risk of type 2 diabetes [J].

Altshuler, D ;

Hirschhorn, JN ;

Klannemark, M ;

Lindgren, CM ;

Vohl, MC ;

Nemesh, J ;

Lane, CR ;

Schaffner, SF ;

Bolk, S ;

Brewer, C ;

Tuomi, T ;

Gaudet, D ;

Hudson, TJ ;

Daly, M ;

Groop, L ;

Lander, ES .

NATURE GENETICS, 2000, 26 (01) :76-80

[3] Measuring European population stratification with microarray genotype data [J].

Bauchet, Marc ;

McEvoy, Brian ;

Pearson, Laurel N. ;

Quillen, Ellen E. ;

Sarkisian, Tamara ;

Hovhannesyan, Kristine ;

Deka, Ranjan ;

Bradley, Daniel G. ;

Shriver, Mark D. .

AMERICAN JOURNAL OF HUMAN GENETICS, 2007, 80 (05) :948-956

[4] Contribution of factor VII genotype to activated FVII levels - Differences in genotype frequencies between northern and southern European populations [J].

Bernardi, F ;

Arcieri, P ;

Bertina, RM ;

Chiarotti, F ;

Corral, J ;

Pinotti, M ;

Prydz, H ;

Samama, M ;

Sandset, PM ;

Strom, R ;

Garcia, VV ;

Mariani, G .

ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 1997, 17 (11) :2548-2553

[5]

Brittingham Angela, 2004, ANCESTRY 2000

[6] Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls [J].

Burton, Paul R. ;

Clayton, David G. ;

Cardon, Lon R. ;

Craddock, Nick ;

Deloukas, Panos ;

Duncanson, Audrey ;

Kwiatkowski, Dominic P. ;

McCarthy, Mark I. ;

Ouwehand, Willem H. ;

Samani, Nilesh J. ;

Todd, John A. ;

Donnelly, Peter ;

Barrett, Jeffrey C. ;

Davison, Dan ;

Easton, Doug ;

Evans, David ;

Leung, Hin-Tak ;

Marchini, Jonathan L. ;

Morris, Andrew P. ;

Spencer, Chris C. A. ;

Tobin, Martin D. ;

Attwood, Antony P. ;

Boorman, James P. ;

Cant, Barbara ;

Everson, Ursula ;

Hussey, Judith M. ;

Jolley, Jennifer D. ;

Knight, Alexandra S. ;

Koch, Kerstin ;

Meech, Elizabeth ;

Nutland, Sarah ;

Prowse, Christopher V. ;

Stevens, Helen E. ;

Taylor, Niall C. ;

Walters, Graham R. ;

Walker, Neil M. ;

Watkins, Nicholas A. ;

Winzer, Thilo ;

Jones, Richard W. ;

McArdle, Wendy L. ;

Ring, Susan M. ;

Strachan, David P. ;

Pembrey, Marcus ;

Breen, Gerome ;

St Clair, David ;

Caesar, Sian ;

Gordon-Smith, Katherine ;

Jones, Lisa ;

Fraser, Christine ;

Green, Elain K. .

NATURE, 2007, 447 (7145) :661-678

[7] Demonstrating stratification in a European American population [J].

Campbell, CD ;

Ogburn, EL ;

Lunetta, KL ;

Lyon, HN ;

Freedman, ML ;

Groop, LC ;

Altshuler, D ;

Ardlie, KG ;

Hirschhorn, JN .

NATURE GENETICS, 2005, 37 (08) :868-872

[8] Population structure in the Mediterranean basin:: A Y chromosome perspective [J].

Capelli, C ;

Redhead, N ;

Romano, V ;

Calì, F ;

Lefranc, G ;

Delague, V ;

Megarbane, A ;

Felice, AE ;

Pascali, VL ;

Neophytou, PI ;

Poulli, Z ;

Novelletto, A ;

Malaspina, P ;

Terrenato, L ;

Berebbi, A ;

Fellous, M ;

Thomas, MG ;

Goldstein, DB .

ANNALS OF HUMAN GENETICS, 2006, 70 :207-225

[9]

Cavalli-Sforza L.L., 1994, HIST GEOGRAPHY HUMAN

[10] Population structure, differential bias and genomic control in a large-scale, case-control association study [J].

Clayton, DG ;

Walker, NM ;

Smyth, DJ ;

Pask, R ;

Cooper, JD ;

Maier, LM ;

Smink, LJ ;

Lam, AC ;

Ovington, NR ;

Stevens, HE ;

Nutland, S ;

Howson, JMM ;

Faham, M ;

Moorhead, M ;

Jones, HB ;

Falkowski, M ;

Hardenbol, P ;

Willis, TD ;

Todd, JA .

NATURE GENETICS, 2005, 37 (11) :1243-1246

← 1 2 3 4 →