Investigation of the fine structure of European populations with applications to disease association studies

被引：129

作者：

Heath, Simon C. ^{[1
]}

Gut, Ivo G. ^{[1
]}

Brennan, Paul ^{[2
]}

McKay, James D. ^{[2
]}

Bencko, Vladimir ^{[3
]}

Fabianova, Eleonora ^{[4
]}

Foretova, Lenka ^{[5
]}

Georges, Michel ^{[6
]}

Janout, Vladimir ^{[7
]}

Kabesch, Michael ^{[8
]}

Krokan, Hans E. ^{[9
]}

Elvestad, Maiken B. ^{[9
]}

Lissowska, Jolanta ^{[10
,11
]}

Mates, Dana ^{[12
]}

Rudnai, Peter ^{[13
]}

Skorpen, Frank ^{[14
]}

Schreiber, Stefan ^{[15
]}

Soria, Jose M. ^{[16
]}

Syvanen, Ann-Christine ^{[17
]}

Meneton, Pierre ^{[18
]}

Hercberg, Serge ^{[19
,20
]}

Galan, Pilar ^{[19
,20
]}

Szeszenia-Dabrowska, Neonilia ^{[21
]}

Zaridze, David ^{[22
]}

Genin, Emmanuel ^{[23
]}

Cardon, Lon R. ^{[24
]}

Lathrop, Mark

机构：

[1] CEA, Inst Genom, Ctr Natl Genotypage, F-91000 Evry, France

[2] Int Agcy Res Canc, F-69372 Lyon, France

[3] Charles Univ Prague, Fac Med 1, Inst Hyg & Epidemiol, Prague, Czech Republic

[4] Specialized Inst Hyg & Epidemiol, Banska Bystrica, Slovakia

[5] Masaryk Mem Canc Inst, Dept Canc Epidemiol & Genet, Brno, Czech Republic

[6] Univ Liege, GIGA Res & Dept Anim Sci, Fac Vet Med, Unit Anim Genom, Liege, Belgium

[7] Palacky Univ, Dept Prevent Med, CR-77147 Olomouc, Czech Republic

[8] Univ Munich, Univ Childrens Hosp, Munich, Germany

[9] Norwegian Univ Sci & Technol, Dept Canc Res & Mol Med, Fac Med, N-7034 Trondheim, Norway

[10] SklodowskaCurie Mem Canc Ctr, Warsaw, Poland

[11] Inst Oncol, Warsaw, Poland

[12] Inst Publ Hlth, Bucharest, Romania

[13] Natl Inst Environm Hlth, Budapest, Hungary

[14] Norwegian Univ Sci & Technol, Dept Lab Med Childrens & Womens Hlth, Fac Med, N-7034 Trondheim, Norway

[15] Univ Kiel, PopGen Biobank, Inst Clin Mol Biol, Kiel, Germany

[16] Hosp Santa Creu & Sant Pau, Inst Rec, Unitat Genom Malaties Complexes, Barcelona, Spain

[17] Uppsala Univ, Dept Med Sci, Uppsala, Sweden

[18] Ctr Rech Cordeliers, INSERM, U872, Paris, France

[19] INSERM, U557, Bobigny, France

[20] Unite Rech Epidemiol Nutr, Bobigny, France

[21] Inst Occupat Med, Dept Epidemiol, Lodz, Poland

[22] Inst Carcinogenesis, Canc Res Ctr, Moscow, Russia

[23] Fdn Jean Dausset CEPH, INSERM, U794, Paris, France

[24] GlaxoSmithKline Inc, King Of Prussia, PA USA

来源：

EUROPEAN JOURNAL OF HUMAN GENETICS | 2008年 / 16卷 / 12期

基金：

英国惠康基金; 瑞典研究理事会;

关键词：

PCA; GWAS; European; population; association; structure;

D O I：

10.1038/ejhg.2008.210

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

An investigation into fine-scale European population structure was carried out using high-density genetic variation on nearly 6000 individuals originating from across Europe. The individuals were collected as control samples and were genotyped with more than 300 000 SNPs in genome-wide association studies using the Illumina Infinium platform. A major East-West gradient from Russian (Moscow) samples to Spanish samples was identified as the first principal component (PC) of the genetic diversity. The second PC identified a North-South gradient from Norway and Sweden to Romania and Spain. Variation of frequencies at markers in three separate genomic regions, surrounding LCT, HLA and HERC2, were strongly associated with this gradient. The next 18 PCs also accounted for a significant proportion of genetic diversity observed in the sample. We present a method to predict the ethnic origin of samples by comparing the sample genotypes with those from a reference set of samples of known origin. These predictions can be performed using just summary information on the known samples, and individual genotype data are not required. We discuss issues raised by these data and analyses for association studies including the matching of case-only cohorts to appropriate pre-collected control samples for genome-wide association studies.

引用

页码：1413 / 1429

页数：17

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