Integrating common and rare genetic variation in diverse human populations

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

doi:10.1038/nature09298

Integrating common and rare genetic variation in diverse human populations

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

Original language	English
Pages (from-to)	52-58
Number of pages	7
Journal	Nature
Volume	467
Issue number	7311
DOIs	https://doi.org/10.1038/nature09298
Publication status	Published - 2 Sept 2010

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Altshuler, D., Gibbs, R., Peltonen, L., Dermitzakis, E., Schaffner, S., Yu, F., Bonnen, P., de Bakker, P., Deloukas, P., Gabriel, S., Gwilliam, R., Hunt, S., Inouye, M., Jia, X., Palotie, A., Parkin, M., Whittaker, P., Chang, K., Hawes, A., ... McEwen, J. (2010). Integrating common and rare genetic variation in diverse human populations. Nature, 467(7311), 52-58. https://doi.org/10.1038/nature09298

@article{08bba22282b24fb680a3765575fca512,

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#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.",

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

year = "2010",

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day = "2",

doi = "10.1038/nature09298",

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Altshuler, D, Gibbs, R, Peltonen, L, Dermitzakis, E, Schaffner, S, Yu, F, Bonnen, P, de Bakker, P, Deloukas, P, Gabriel, S, Gwilliam, R, Hunt, S, Inouye, M, Jia, X, Palotie, A, Parkin, M, Whittaker, P, Chang, K, Hawes, A, Lewis, L, Ren, Y, Wheeler, D, Muzny, D, Barnes, C, Darvishi, K, Hurles, M, Korn, J, Kristiansson, K, Lee, C, McCarroll, S, Nemesh, J, Keinan, A, Montgomery, S, Pollack, S, Price, A, Soranzo, N, Gonzaga-Jauregui, C, Antilla, V, Brodeur, W, Daly, M, Leslie, S, McVean, G, Moutsianas, L, Nguyen, H, Zhang, Q, Ghori, M, McGinnis, R, McLaren, W, Takeuchi, F, Grossman, S, Shlyakhter, I, Hostetter, E, Sabeti, P, Adebamowo, C, Foster, M, Gordon, D, Licinio, J, Manca, M, Marshall, P, Matsuda, I, Ngare, D, Wang, V, Reddy, D, Rotimi, C, Royal, C, Sharp, R, Zeng, C, Brooks, L & McEwen, J 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

TY - JOUR

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

AU - Altshuler, David

AU - Gibbs, Richard

AU - Peltonen, Leena

AU - Dermitzakis, Emmanouil

AU - Schaffner, Stephen

AU - Yu, Fuli

AU - Bonnen, Penelope

AU - de Bakker, Paul

AU - Deloukas, Panos

AU - Gabriel, Stacey

AU - Gwilliam, Rhian

AU - Hunt, Sarah

AU - Inouye, Michael

AU - Jia, Xiaoming

AU - Palotie, Aarno

AU - Parkin, Melissa

AU - Whittaker, Pamela

AU - Chang, Kyle

AU - Hawes, Alicia

AU - Lewis, Lora

AU - Ren, Yanru

AU - Wheeler, David

AU - Muzny, Donna

AU - Barnes, Chris

AU - Darvishi, Katayoon

AU - Hurles, Matthew

AU - Korn, Joshua

AU - Kristiansson, Kati

AU - Lee, Charles

AU - McCarroll, Steven

AU - Nemesh, James

AU - Keinan, Alon

AU - Montgomery, Stephen

AU - Pollack, Samuela

AU - Price, Alkes

AU - Soranzo, Nicole

AU - Gonzaga-Jauregui, Claudia

AU - Antilla, Verneri

AU - Brodeur, Wendy

AU - Daly, Mark

AU - Leslie, Stephen

AU - McVean, Gil

AU - Moutsianas, Loukas

AU - Nguyen, Huy

AU - Zhang, Qingrun

AU - Ghori, Mohammed

AU - McGinnis, Ralph

AU - McLaren, William

AU - Takeuchi, Fumihiko

AU - Grossman, Sharon

AU - Shlyakhter, Ilya

AU - Hostetter, Elizabeth

AU - Sabeti, Pardis

AU - Adebamowo, Clement

AU - Foster, Morris

AU - Gordon, Deborah

AU - Licinio, Julio

AU - Manca, Maria

AU - Marshall, Patricia

AU - Matsuda, Ichiro

AU - Ngare, Duncan

AU - Wang, Vivian

AU - Reddy, Deepa

AU - Rotimi, Charles

AU - Royal, Charmaine

AU - Sharp, Richard

AU - Zeng, Changqing

AU - Brooks, Lisa

AU - McEwen, Jean

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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U2 - 10.1038/nature09298

DO - 10.1038/nature09298

M3 - Article

SN - 0028-0836

VL - 467

SP - 52

EP - 58

JO - Nature

JF - Nature

IS - 7311

ER -

Integrating common and rare genetic variation in diverse human populations

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