Integrating common and rare genetic variation in diverse human populations

David M. Altshuler, Richard A. Gibbs, Leena Peltonen, Stephen F. Schaffner, Fuli Yu, Emmanouil Dermitzakis, Penelope E. Bonnen, Paul I W De Bakker, Panos Deloukas, Stacey B. Gabriel, Rhian Gwilliam, Sarah Hunt, Michael Inouye, Xiaoming Jia, Palotie Aarno Palotie, Melissa Parkin, Pamela Whittaker, Kyle Chang, Alicia Hawes, Lora R. Lewis & 50 others Yanru Ren, David Wheeler, Donna Marie Muzny, Chris Barnes, Katayoon Darvishi, Matthew Hurles, Joshua M. Korn, Kati Kristiansson, Charles Lee, Steven A. McCarroll, James Nemesh, Alon Keinan, Stephen B. Montgomery, Pollack Samuela Pollack, Alkes L. Price, Nicole Soranzo, Claudia Gonzaga-Jauregui, Verneri Anttila, Wendy Brodeur, Mark J. Daly, Stephen Leslie, Gil McVean, Loukas Moutsianas, Huy Nguyen, Qingrun Zhang, Mohammed J R Ghori, Ralph McGinnis, William McLaren, Samuela Pollack, Fumihiko Takeuchi, Sharon R. Grossman, Ilya Shlyakhter, Elizabeth B. Hostetter, Pardis C. Sabeti, Clement A. Adebamowo, Morris W. Foster, Deborah R. Gordon, Julio Licinio, Maria Cristina Manca, Patricia A. Marshall, Ichiro Matsuda, Duncan Ngare, Vivian Ota Wang, Deepa Reddy, Charles N. Rotimi, Charmaine D. Royal, Richard R. Sharp, Changqing Zeng, D. B. Brooks, Jean E. McEwen

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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#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.

LanguageEnglish
Pages52-58
Number of pages7
JournalNature
Volume467
Issue number7311
DOIs
Publication statusPublished - 2 Sep 2010

ASJC Scopus subject areas

  • General

Cite this

Altshuler, D. M., Gibbs, R. A., Peltonen, L., Schaffner, S. F., Yu, F., Dermitzakis, E., ... McEwen, J. E. (2010). Integrating common and rare genetic variation in diverse human populations. Nature, 467(7311), 52-58. https://doi.org/10.1038/nature09298
Altshuler, David M. ; Gibbs, Richard A. ; Peltonen, Leena ; Schaffner, Stephen F. ; Yu, Fuli ; Dermitzakis, Emmanouil ; Bonnen, Penelope E. ; De Bakker, Paul I W ; Deloukas, Panos ; Gabriel, Stacey B. ; Gwilliam, Rhian ; Hunt, Sarah ; Inouye, Michael ; Jia, Xiaoming ; Aarno Palotie, Palotie ; Parkin, Melissa ; Whittaker, Pamela ; Chang, Kyle ; Hawes, Alicia ; Lewis, Lora R. ; Ren, Yanru ; Wheeler, David ; Muzny, Donna Marie ; Barnes, Chris ; Darvishi, Katayoon ; Hurles, Matthew ; Korn, Joshua M. ; Kristiansson, Kati ; Lee, Charles ; McCarroll, Steven A. ; Nemesh, James ; Keinan, Alon ; Montgomery, Stephen B. ; Samuela Pollack, Pollack ; Price, Alkes L. ; Soranzo, Nicole ; Gonzaga-Jauregui, Claudia ; Anttila, Verneri ; Brodeur, Wendy ; Daly, Mark J. ; Leslie, Stephen ; McVean, Gil ; Moutsianas, Loukas ; Nguyen, Huy ; Zhang, Qingrun ; Ghori, Mohammed J R ; McGinnis, Ralph ; McLaren, William ; Pollack, Samuela ; Takeuchi, Fumihiko ; Grossman, Sharon R. ; Shlyakhter, Ilya ; Hostetter, Elizabeth B. ; Sabeti, Pardis C. ; Adebamowo, Clement A. ; Foster, Morris W. ; Gordon, Deborah R. ; Licinio, Julio ; Manca, Maria Cristina ; Marshall, Patricia A. ; Matsuda, Ichiro ; Ngare, Duncan ; Wang, Vivian Ota ; Reddy, Deepa ; Rotimi, Charles N. ; Royal, Charmaine D. ; Sharp, Richard R. ; Zeng, Changqing ; Brooks, D. B. ; McEwen, Jean E. / Integrating common and rare genetic variation in diverse human populations. In: Nature. 2010 ; Vol. 467, No. 7311. pp. 52-58.
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Altshuler, DM, Gibbs, RA, Peltonen, L, Schaffner, SF, Yu, F, Dermitzakis, E, Bonnen, PE, De Bakker, PIW, Deloukas, P, Gabriel, SB, Gwilliam, R, Hunt, S, Inouye, M, Jia, X, Aarno Palotie, P, Parkin, M, Whittaker, P, Chang, K, Hawes, A, Lewis, LR, Ren, Y, Wheeler, D, Muzny, DM, Barnes, C, Darvishi, K, Hurles, M, Korn, JM, Kristiansson, K, Lee, C, McCarroll, SA, Nemesh, J, Keinan, A, Montgomery, SB, Samuela Pollack, P, Price, AL, Soranzo, N, Gonzaga-Jauregui, C, Anttila, V, Brodeur, W, Daly, MJ, Leslie, S, McVean, G, Moutsianas, L, Nguyen, H, Zhang, Q, Ghori, MJR, McGinnis, R, McLaren, W, Pollack, S, Takeuchi, F, Grossman, SR, Shlyakhter, I, Hostetter, EB, Sabeti, PC, Adebamowo, CA, Foster, MW, Gordon, DR, Licinio, J, Manca, MC, Marshall, PA, Matsuda, I, Ngare, D, Wang, VO, Reddy, D, Rotimi, CN, Royal, CD, Sharp, RR, Zeng, C, Brooks, DB & McEwen, JE 2010, 'Integrating common and rare genetic variation in diverse human populations', Nature, vol. 467, no. 7311, pp. 52-58. https://doi.org/10.1038/nature09298

Integrating common and rare genetic variation in diverse human populations. / Altshuler, David M.; Gibbs, Richard A.; Peltonen, Leena; Schaffner, Stephen F.; Yu, Fuli; Dermitzakis, Emmanouil; Bonnen, Penelope E.; De Bakker, Paul I W; Deloukas, Panos; Gabriel, Stacey B.; Gwilliam, Rhian; Hunt, Sarah; Inouye, Michael; Jia, Xiaoming; Aarno Palotie, Palotie; Parkin, Melissa; Whittaker, Pamela; Chang, Kyle; Hawes, Alicia; Lewis, Lora R.; Ren, Yanru; Wheeler, David; Muzny, Donna Marie; Barnes, Chris; Darvishi, Katayoon; Hurles, Matthew; Korn, Joshua M.; Kristiansson, Kati; Lee, Charles; McCarroll, Steven A.; Nemesh, James; Keinan, Alon; Montgomery, Stephen B.; Samuela Pollack, Pollack; Price, Alkes L.; Soranzo, Nicole; Gonzaga-Jauregui, Claudia; Anttila, Verneri; Brodeur, Wendy; Daly, Mark J.; Leslie, Stephen; McVean, Gil; Moutsianas, Loukas; Nguyen, Huy; Zhang, Qingrun; Ghori, Mohammed J R; McGinnis, Ralph; McLaren, William; Pollack, Samuela; Takeuchi, Fumihiko; Grossman, Sharon R.; Shlyakhter, Ilya; Hostetter, Elizabeth B.; Sabeti, Pardis C.; Adebamowo, Clement A.; Foster, Morris W.; Gordon, Deborah R.; Licinio, Julio; Manca, Maria Cristina; Marshall, Patricia A.; Matsuda, Ichiro; Ngare, Duncan; Wang, Vivian Ota; Reddy, Deepa; Rotimi, Charles N.; Royal, Charmaine D.; Sharp, Richard R.; Zeng, Changqing; Brooks, D. B.; McEwen, Jean E.

In: Nature, Vol. 467, No. 7311, 02.09.2010, p. 52-58.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Integrating common and rare genetic variation in diverse human populations

AU - Altshuler, David M.

AU - Gibbs, Richard A.

AU - Peltonen, Leena

AU - Schaffner, Stephen F.

AU - Yu, Fuli

AU - Dermitzakis, Emmanouil

AU - Bonnen, Penelope E.

AU - De Bakker, Paul I W

AU - Deloukas, Panos

AU - Gabriel, Stacey B.

AU - Gwilliam, Rhian

AU - Hunt, Sarah

AU - Inouye, Michael

AU - Jia, Xiaoming

AU - Aarno Palotie, Palotie

AU - Parkin, Melissa

AU - Whittaker, Pamela

AU - Chang, Kyle

AU - Hawes, Alicia

AU - Lewis, Lora R.

AU - Ren, Yanru

AU - Wheeler, David

AU - Muzny, Donna Marie

AU - Barnes, Chris

AU - Darvishi, Katayoon

AU - Hurles, Matthew

AU - Korn, Joshua M.

AU - Kristiansson, Kati

AU - Lee, Charles

AU - McCarroll, Steven A.

AU - Nemesh, James

AU - Keinan, Alon

AU - Montgomery, Stephen B.

AU - Samuela Pollack, Pollack

AU - Price, Alkes L.

AU - Soranzo, Nicole

AU - Gonzaga-Jauregui, Claudia

AU - Anttila, Verneri

AU - Brodeur, Wendy

AU - Daly, Mark J.

AU - Leslie, Stephen

AU - McVean, Gil

AU - Moutsianas, Loukas

AU - Nguyen, Huy

AU - Zhang, Qingrun

AU - Ghori, Mohammed J R

AU - McGinnis, Ralph

AU - McLaren, William

AU - Pollack, Samuela

AU - Takeuchi, Fumihiko

AU - Grossman, Sharon R.

AU - Shlyakhter, Ilya

AU - Hostetter, Elizabeth B.

AU - Sabeti, Pardis C.

AU - Adebamowo, Clement A.

AU - Foster, Morris W.

AU - Gordon, Deborah R.

AU - Licinio, Julio

AU - Manca, Maria Cristina

AU - Marshall, Patricia A.

AU - Matsuda, Ichiro

AU - Ngare, Duncan

AU - Wang, Vivian Ota

AU - Reddy, Deepa

AU - Rotimi, Charles N.

AU - Royal, Charmaine D.

AU - Sharp, Richard R.

AU - Zeng, Changqing

AU - Brooks, D. B.

AU - McEwen, Jean E.

PY - 2010/9/2

Y1 - 2010/9/2

N2 - 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#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.

AB - 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#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.

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Altshuler DM, Gibbs RA, Peltonen L, Schaffner SF, Yu F, Dermitzakis E et al. Integrating common and rare genetic variation in diverse human populations. Nature. 2010 Sep 2;467(7311):52-58. https://doi.org/10.1038/nature09298