Integrating common and rare genetic variation in diverse human populations.
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.
Broad Institute, 7 Cambridge Center, Cambridge, Massachusetts 02138, USA. altshuler@molbio.mgh.harvard.edu
Altshuler
David M
DM
Gibbs
Richard A
RA
Peltonen
Leena
L
Altshuler
David M
DM
Gibbs
Richard A
RA
Peltonen
Leena
L
Dermitzakis
Emmanouil
E
Schaffner
Stephen F
SF
Yu
Fuli
F
Peltonen
Leena
L
Dermitzakis
Emmanouil
E
Bonnen
Penelope E
PE
Altshuler
David M
DM
Gibbs
Richard A
RA
de Bakker
Paul I W
PI
Deloukas
Panos
P
Gabriel
Stacey B
SB
Gwilliam
Rhian
R
Hunt
Sarah
S
Inouye
Michael
M
Jia
Xiaoming
X
Palotie
Aarno
A
Parkin
Melissa
M
Whittaker
Pamela
P
Yu
Fuli
F
Chang
Kyle
K
Hawes
Alicia
A
Lewis
Lora R
LR
Ren
Yanru
Y
Wheeler
David
D
Gibbs
Richard A
RA
Muzny
Donna Marie
DM
Barnes
Chris
C
Darvishi
Katayoon
K
Hurles
Matthew
M
Korn
Joshua M
JM
Kristiansson
Kati
K
Lee
Charles
C
McCarrol
Steven A
SA
Nemesh
James
J
Dermitzakis
Emmanouil
E
Keinan
Alon
A
Montgomery
Stephen B
SB
Pollack
Samuela
S
Price
Alkes L
AL
Soranzo
Nicole
N
Bonnen
Penelope E
PE
Gibbs
Richard A
RA
Gonzaga-Jauregui
Claudia
C
Keinan
Alon
A
Price
Alkes L
AL
Yu
Fuli
F
Anttila
Verneri
V
Brodeur
Wendy
W
Daly
Mark J
MJ
Leslie
Stephen
S
McVean
Gil
G
Moutsianas
Loukas
L
Nguyen
Huy
H
Schaffner
Stephen F
SF
Zhang
Qingrun
Q
Ghori
Mohammed J R
MJ
McGinnis
Ralph
R
McLaren
William
W
Pollack
Samuela
S
Price
Alkes L
AL
Schaffner
Stephen F
SF
Takeuchi
Fumihiko
F
Grossman
Sharon R
SR
Shlyakhter
Ilya
I
Hostetter
Elizabeth B
EB
Sabeti
Pardis C
PC
Adebamowo
Clement A
CA
Foster
Morris W
MW
Gordon
Deborah R
DR
Licinio
Julio
J
Manca
Maria Cristina
MC
Marshall
Patricia A
PA
Matsuda
Ichiro
I
Ngare
Duncan
D
Wang
Vivian Ota
VO
Reddy
Deepa
D
Rotimi
Charles N
CN
Royal
Charmaine D
CD
Sharp
Richard R
RR
Zeng
Changqing
C
Brooks
Lisa D
LD
McEwen
Jean E
JE
D056915:DNA Copy Number Variations; D015894:Genome, Human; D016045:Human Genome Project; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D044382:Population Groups / Q000235:genetics*
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