title: Integrating common and rare genetic variation in diverse human populations.
abstract: Despite great progress in identifying genetic variants that influence human disease, most inherited risk remains unexplained. A more complete understanding requires genome-wide studies that fully examine less common alleles in populations with a wide range of ancestry. To inform the design and interpretation of such studies, we genotyped 1.6 million common single nucleotide polymorphisms (SNPs) in 1,184 reference individuals from 11 global populations, and sequenced ten 100-kilobase regions in 692 of these individuals. This integrated data set of common and rare alleles, called 'HapMap 3', includes both SNPs and copy number polymorphisms (CNPs). We characterized population-specific differences among low-frequency variants, measured the improvement in imputation accuracy afforded by the larger reference panel, especially in imputing SNPs with a minor allele frequency of <or=5%, and demonstrated the feasibility of imputing newly discovered CNPs and SNPs. This expanded public resource of genome variants in global populations supports deeper interrogation of genomic variation and its role in human disease, and serves as a step towards a high-resolution map of the landscape of human genetic variation.
authors.affiliation: Broad Institute, 7 Cambridge Center, Cambridge, Massachusetts 02138, USA. altshuler@molbio.mgh.harvard.edu
authors.forename: David M
authors.initials: DM
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authors.forename: Richard A
authors.initials: RA
authors.lastname: Gibbs
authors.forename: Leena
authors.initials: L
authors.lastname: Peltonen
authors.forename: David M
authors.initials: DM
authors.lastname: Altshuler
authors.forename: Richard A
authors.initials: RA
authors.lastname: Gibbs
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authors.initials: L
authors.lastname: Peltonen
authors.forename: Emmanouil
authors.initials: E
authors.lastname: Dermitzakis
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Schaffner
authors.forename: Fuli
authors.initials: F
authors.lastname: Yu
authors.forename: Leena
authors.initials: L
authors.lastname: Peltonen
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authors.initials: E
authors.lastname: Dermitzakis
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authors.initials: PE
authors.lastname: Bonnen
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authors.initials: DM
authors.lastname: Altshuler
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authors.initials: RA
authors.lastname: Gibbs
authors.forename: Paul I W
authors.initials: PI
authors.lastname: de Bakker
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authors.initials: P
authors.lastname: Deloukas
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authors.lastname: Gwilliam
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authors.initials: S
authors.lastname: Hunt
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authors.initials: M
authors.lastname: Inouye
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authors.lastname: Jia
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authors.initials: A
authors.lastname: Palotie
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authors.initials: M
authors.lastname: Parkin
authors.forename: Pamela
authors.initials: P
authors.lastname: Whittaker
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authors.initials: F
authors.lastname: Yu
authors.forename: Kyle
authors.initials: K
authors.lastname: Chang
authors.forename: Alicia
authors.initials: A
authors.lastname: Hawes
authors.forename: Lora R
authors.initials: LR
authors.lastname: Lewis
authors.forename: Yanru
authors.initials: Y
authors.lastname: Ren
authors.forename: David
authors.initials: D
authors.lastname: Wheeler
authors.forename: Richard A
authors.initials: RA
authors.lastname: Gibbs
authors.forename: Donna Marie
authors.initials: DM
authors.lastname: Muzny
authors.forename: Chris
authors.initials: C
authors.lastname: Barnes
authors.forename: Katayoon
authors.initials: K
authors.lastname: Darvishi
authors.forename: Matthew
authors.initials: M
authors.lastname: Hurles
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Korn
authors.forename: Kati
authors.initials: K
authors.lastname: Kristiansson
authors.forename: Charles
authors.initials: C
authors.lastname: Lee
authors.forename: Steven A
authors.initials: SA
authors.lastname: McCarrol
authors.forename: James
authors.initials: J
authors.lastname: Nemesh
authors.forename: Emmanouil
authors.initials: E
authors.lastname: Dermitzakis
authors.forename: Alon
authors.initials: A
authors.lastname: Keinan
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Montgomery
authors.forename: Samuela
authors.initials: S
authors.lastname: Pollack
authors.forename: Alkes L
authors.initials: AL
authors.lastname: Price
authors.forename: Nicole
authors.initials: N
authors.lastname: Soranzo
authors.forename: Penelope E
authors.initials: PE
authors.lastname: Bonnen
authors.forename: Richard A
authors.initials: RA
authors.lastname: Gibbs
authors.forename: Claudia
authors.initials: C
authors.lastname: Gonzaga-Jauregui
authors.forename: Alon
authors.initials: A
authors.lastname: Keinan
authors.forename: Alkes L
authors.initials: AL
authors.lastname: Price
authors.forename: Fuli
authors.initials: F
authors.lastname: Yu
authors.forename: Verneri
authors.initials: V
authors.lastname: Anttila
authors.forename: Wendy
authors.initials: W
authors.lastname: Brodeur
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Daly
authors.forename: Stephen
authors.initials: S
authors.lastname: Leslie
authors.forename: Gil
authors.initials: G
authors.lastname: McVean
authors.forename: Loukas
authors.initials: L
authors.lastname: Moutsianas
authors.forename: Huy
authors.initials: H
authors.lastname: Nguyen
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Schaffner
authors.forename: Qingrun
authors.initials: Q
authors.lastname: Zhang
authors.forename: Mohammed J R
authors.initials: MJ
authors.lastname: Ghori
authors.forename: Ralph
authors.initials: R
authors.lastname: McGinnis
authors.forename: William
authors.initials: W
authors.lastname: McLaren
authors.forename: Samuela
authors.initials: S
authors.lastname: Pollack
authors.forename: Alkes L
authors.initials: AL
authors.lastname: Price
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Schaffner
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Takeuchi
authors.forename: Sharon R
authors.initials: SR
authors.lastname: Grossman
authors.forename: Ilya
authors.initials: I
authors.lastname: Shlyakhter
authors.forename: Elizabeth B
authors.initials: EB
authors.lastname: Hostetter
authors.forename: Pardis C
authors.initials: PC
authors.lastname: Sabeti
authors.forename: Clement A
authors.initials: CA
authors.lastname: Adebamowo
authors.forename: Morris W
authors.initials: MW
authors.lastname: Foster
authors.forename: Deborah R
authors.initials: DR
authors.lastname: Gordon
authors.forename: Julio
authors.initials: J
authors.lastname: Licinio
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Manca
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Marshall
authors.forename: Ichiro
authors.initials: I
authors.lastname: Matsuda
authors.forename: Duncan
authors.initials: D
authors.lastname: Ngare
authors.forename: Vivian Ota
authors.initials: VO
authors.lastname: Wang
authors.forename: Deepa
authors.initials: D
authors.lastname: Reddy
authors.forename: Charles N
authors.initials: CN
authors.lastname: Rotimi
authors.forename: Charmaine D
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authors.lastname: Royal
authors.forename: Richard R
authors.initials: RR
authors.lastname: Sharp
authors.forename: Changqing
authors.initials: C
authors.lastname: Zeng
authors.forename: Lisa D
authors.initials: LD
authors.lastname: Brooks
authors.forename: Jean E
authors.initials: JE
authors.lastname: McEwen
mesh_terms: D056915:DNA Copy Number Variations; D015894:Genome, Human; D016045:Human Genome Project; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D044382:Population Groups / Q000235:genetics*
references.citation: Science. 2005 Dec 16;310(5755):1782-6
references.pmid: 16357253
references.citation: Nat Genet. 2008 Oct;40(10):1166-74
references.pmid: 18776908
references.citation: Nature. 2010 Apr 1;464(7289):704-12
references.pmid: 19812545
references.citation: Nat Genet. 2007 Oct;39(10):1251-5
references.pmid: 17828266
references.citation: Nat Genet. 2008 Oct;40(10):1245-52
references.pmid: 18776912
references.citation: Genome Res. 2009 May;19(5):711-22
references.pmid: 19411596
references.citation: Nature. 2008 Dec 11;456(7223):728-31
references.pmid: 19079049
references.citation: Bioinformatics. 2007 Oct 15;23(20):2741-6
references.pmid: 17846035
references.citation: Nature. 2001 Feb 15;409(6822):860-921
references.pmid: 11237011
references.citation: Nature. 2009 Oct 8;461(7265):747-53
references.pmid: 19812666
references.citation: Nat Genet. 2007 Jul;39(7):827-9
references.pmid: 17558408
references.citation: Nat Genet. 2008 Oct;40(10):1253-60
references.pmid: 18776909
references.citation: PLoS One. 2009 Jun 02;4(6):e5767
references.pmid: 19503617
references.citation: Nucleic Acids Res. 2007;35(6):2013-25
references.pmid: 17341461
references.citation: Annu Rev Genomics Hum Genet. 2008;9:403-33
references.pmid: 18593304
references.citation: Genome Res. 2009 May;19(5):826-37
references.pmid: 19307593
references.citation: Nature. 2005 Oct 27;437(7063):1299-320
references.pmid: 16255080
references.citation: Science. 2006 Jun 16;312(5780):1614-20
references.pmid: 16778047
references.citation: Nature. 2001 Feb 15;409(6822):928-33
references.pmid: 11237013
references.citation: Science. 2010 Feb 12;327(5967):883-6
references.pmid: 20056855
references.citation: Nature. 2007 Jun 7;447(7145):661-78
references.pmid: 17554300
references.citation: Nature. 2007 Oct 18;449(7164):851-61
references.pmid: 17943122
references.citation: Genome Res. 2005 Nov;15(11):1553-65
references.pmid: 16251465
references.citation: PLoS Comput Biol. 2005 Oct;1(5):e53
references.pmid: 16261194
references.citation: Nature. 2006 Nov 23;444(7118):444-54
references.pmid: 17122850
references.citation: Am J Hum Genet. 2006 Apr;78(4):588-603
references.pmid: 16532390