Integrating common and rare genetic variation in diverse human populations (original) (raw)
References
- International Human Genome Sequencing Consortium.. Initial sequencing and analysis of the human genome. Nature 409, 860–921 (2001)
- The Internation SNP Map Working Group.. A map of human genome sequence variation containing 1.42 million single nucleotide polymorphisms. Nature 409, 928–933 (2001)
- The International HapMap Consortium. A second generation human haplotype map of over 3.1 million SNPs. Nature 449, 851–861 (2007)
- Donnelly, P. Progress and challenges in genome-wide association studies in humans. Nature 456, 728–731 (2008)
CAS Google Scholar - Manolio, T. A. et al. Finding the missing heritability of complex diseases. Nature 461, 747–753 (2009)
CAS Google Scholar - Korn, J. M. et al. Integrated genotype calling and association analysis of SNPs, common copy number polymorphisms and rare CNVs. Nature Genet. 40, 1253–1260 (2008)
CAS Google Scholar - McCarroll, S. A. et al. Integrated detection and population-genetic analysis of SNPs and copy number variation. Nature Genet. 40, 1166–1174 (2008)
CAS Google Scholar - Barnes, C. et al. A robust statistical method for case-control association testing with copy number variation. Nature Genet. 40, 1245–1252 (2008)
CAS Google Scholar - Redon, R. et al. Global variation in copy number in the human genome. Nature 444, 444–454 (2006)
CAS Google Scholar - Conrad, D. F. et al. Origins and functional impact of copy number variation in the human genome. Nature 464, 704–712 (2010)
CAS Google Scholar - Teo, Y. Y. et al. A genotype calling algorithm for the Illumina BeadArray platform. Bioinformatics 23, 2741–2746 (2007)
CAS Google Scholar - The Internatinal HapMap Consortium. A haplotype map of the human genome. Nature 437, 1299–1320 (2005)
- Zhang, J. et al. SNPdetector: a software tool for sensitive and accurate SNP detection. PLOS Comput. Biol. 1 e53 10.1371/journal.pcbi.0010053 (2005)
CAS Google Scholar - Campbell, M. C. & Tishkoff, S. A. African genetic diversity: implications for human demographic history, modern human origins, and complex disease mapping. Annu. Rev. Genomics Hum. Genet. 9, 403–433 (2008)
CAS Google Scholar - Keinan, A., Mullikin, J. C., Patterson, N. & Reich, D. Measurement of the human allele frequency spectrum demonstrates greater genetic drift in East Asians than in Europeans. Nature Genet. 39, 1251–1255 (2007)
CAS Google Scholar - van Heel, D. A. et al. A genome-wide association study for celiac disease identifies risk variants in the region harboring IL2 and IL21. Nature Genet. 39, 827–829 (2007)
CAS Google Scholar - The Wellcome Trust Case Control Consortium. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 447, 661–678 (2007)
- Pe’er, I. et al. Biases and reconciliation in estimates of linkage disequilibrium in the human genome. Am. J. Hum. Genet. 78, 588–603 (2006)
Google Scholar - Grossman, S. R. et al. A composite of multiple signals distinguishes causal variants in regions of positive selection. Science 327, 883–886 (2010)
CAS Google Scholar - Sabeti, P. C. et al. Positive natural selection in the human lineage. Science 312, 1614–1620 (2006)
CAS Google Scholar - Lamason, R. L. et al. SLC24A5, a putative cation exchanger, affects pigmentation in zebrafish and humans. Science 310, 1782–1786 (2005)
CAS Google Scholar - Akey, J. M. Constructing genomic maps of positive selection in humans: where do we go from here? Genome Res. 19, 711–722 (2009)
CAS Google Scholar - Pickrell, J. K. et al. Signals of recent positive selection in a worldwide sample of human populations. Genome Res. 19, 826–837 (2009)
CAS Google Scholar - Carlson, C. S. et al. Genomic regions exhibiting positive selection identified from dense genotype data. Genome Res. 15, 1553–1565 (2005)
CAS Google Scholar - Gu, J. et al. A genome scan for positive selection in thoroughbred horses. PLoS ONE 4 e5767 10.1371/journal.pone.0005767 (2009)
CAS Google Scholar - Li, Y. & Abecasis, G. R. Mach 1.0: rapid haplotype reconstruction and missing genotype inference. Am. J. Hum. Genet. S79, 2290 (2006)
Google Scholar - Colella, S. et al. QuantiSNP: an Objective Bayes Hidden-Markov Model to detect and accurately map copy number variation using SNP genotyping data. Nucleic Acids Res. 35, 2013–2025 (2007)
CAS Google Scholar
Acknowledgements
We dedicate this work to Leena Peltonen for her vital leadership role in this study, and in memory of a valued friend and colleague. We thank E. Boerwinkle and R. Durbin for critical reading of the manuscript. We thank the USA National Institutes of Health, the National Human Genome Research Institute, the National Institute on Deafness and Other Communication Disorders and the Wellcome Trust for supporting the majority of this work. Funding was also provided by the Louis-Jeantet Foundation and the NCCR ‘Frontiers in Genetics’ (Swiss National Science Foundation). We thank the people from the following communities who were generous in donating their blood samples to be studied in this project: the Yoruba in Ibadan, Nigeria; the Maasai in Kinyawa, Kenya; the Luhya in Webuye, Kenya; the Han Chinese in Beijing, China; the Japanese in Tokyo, Japan; the Chinese in metropolitan Denver, Colorado; the Gujarati Indians in Houston, Texas; the Toscani in Italia; the community of African ancestry in the southwestern USA; and the community of Mexican ancestry in Los Angeles, California. We also thank the people in the Utah Centre d’Etude du Polymorphisme Humain community who allowed the samples they donated earlier to be used for the project. The authors acknowledge use of DNA from the 1958 British birth cohort collection, funded by the UK Medical Research Council grant G0000934 and the Wellcome Trust grant 068545/Z/02. The Illumina 550K genotype data for the 1958 British birth cohort samples were made available by the Sanger Institute. For the 1958 British birth cohort Affymetrix 500K genotype data, we thank the Wellcome Trust Case Control Consortium (http://www.wtccc.org.uk), which was funded by Wellcome Trust award 076113.
Author information
Author notes
- Leena Peltonen, Leena Peltonen and Leena Peltonen: ‡Deceased.
Authors and Affiliations
- Broad Institute, 7 Cambridge Center, Cambridge, Massachusetts 02138, USA.,
David M. Altshuler, David M. Altshuler, Stephen F. Schaffner, David M. Altshuler, Paul I. W. de Bakker (Co-leader), Stacey B. Gabriel, Xiaoming Jia, Melissa Parkin (Co-leader), Joshua M. Korn, Steven A. McCarroll (Co-leader), James Nemesh, Samuela Pollack, Wendy Brodeur, Huy Nguyen, Stephen F. Schaffner (Leader), Samuela Pollack, Stephen F. Schaffner (Co-leader) & Ilya Shlyakhter - Department of Molecular and Human Genetics, Baylor College of Medicine, Human Genome Sequencing Center, One Baylor Plaza, Houston, Texas 77030, USA.,
Richard A. Gibbs, Richard A. Gibbs, Fuli Yu, Penelope E. Bonnen, Richard A. Gibbs, Fuli Yu (Leader), Kyle Chang, Alicia Hawes, Lora R. Lewis, Yanru Ren, David Wheeler, Richard A. Gibbs, Donna Marie Muzny, Penelope E. Bonnen, Richard A. Gibbs, Claudia Gonzaga-Jauregui & Fuli Yu (Leader) - Department of Genetic Medicine and Development, University of Geneva, Medical School, Faculty of Medicine, Geneva 1211, Switzerland.,
Emmanouil Dermitzakis, Emmanouil Dermitzakis, Emmanouil Dermitzakis & Stephen B. Montgomery - Division of Genetics, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.,
Paul I. W. de Bakker (Co-leader) - Department of Human Genetics, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge CB10 1HH, UK.,
Panos Deloukas (Co-leader), Rhian Gwilliam, Sarah Hunt, Michael Inouye (Co-leader), Aarno Palotie, Pamela Whittaker, Chris Barnes, Matthew Hurles (Co-leader), Kati Kristiansson, Nicole Soranzo, Verneri Anttila, Qingrun Zhang, Mohammed J. R. Ghori, Ralph McGinnis (Co-leader), William McLaren & Fumihiko Takeuchi - Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Haartmaninkatu 8, 00290 Helsinki, Finland.,
Aarno Palotie & Verneri Anttila - Department of Medical Genetics, University of Helsinki and University Central Hospital, Haartmaninkatu 8, 00290 Helsinki, Finland.,
Aarno Palotie & Verneri Anttila - Department of Pathology, Harvard Medical School, Brigham and Women’s Hospital, Boston, Massachusetts 02115, USA.,
Katayoon Darvishi & Charles Lee - Department of Biological Statistics and Computational Biology, Cornell University, 102A Weill Hall, Ithaca, New York 14853, USA.,
Alon Keinan (Leader) & Alon Keinan - Departments of Epidemiology and Biostatistics, Harvard School of Public Health, 665 Huntington Avenue, Building 2 Room 211, Boston, Massachusetts 02115, USA.,
Alkes L. Price, Alkes L. Price & Alkes L. Price (Co-leader) - Massachusetts General Hospital, Center for Human Genetic Research, Simches Research Center, 185 Cambridge Street, Boston, Massachusetts 02114, USA.,
Mark J. Daly - Department of Statistics, University of Oxford, 1 South Parks Road, Oxford OX1 3TG, UK.,
Stephen Leslie, Gil McVean & Loukas Moutsianas - Department of Organismic and Evolutionary Biology, Harvard University, Center for Systems Biology, 52 Oxford Street, Room 469, Cambridge, Massachusetts 02215, USA.,
Sharon R. Grossman, Elizabeth B. Hostetter & Pardis C. Sabeti (Leader) - Department of Epidemiology and Preventative Medicine, University of Maryland School of Medicine, N406 Institute of Human Virology, 725 West Lombard Street, Baltimore, Maryland 21201, USA.,
Clement A. Adebamowo - Department of Anthropology, University of Oklahoma, 455 West Lindsey Room 505C, Norman, Oklahoma 73019, USA.,
Morris W. Foster - Department of Anthropology, University of California, San Francisco, History and Social Medicine, 3333 California Street Suite 485, San Francisco, 94143-0850, California, USA
Deborah R. Gordon - The Australian National University, John Curtin School of Medical Research, Garran Road, Building 131, Canberra, ACT2603, Australia.,
Julio Licinio - Institute for Oncological Study and Prevention, 50139, Florence, Italy
Maria Cristina Manca - Department of Bioethics, Case Western Reserve University, School of Medicine TA200, 10900 Euclid Avenue, Cleveland, Ohio 44106-4976, USA.,
Patricia A. Marshall - Health Sciences University of Hokkaido, 1757 Kanazawa, Tobetsu-cho, Ishikari-gun, Hokkaido 061-0293, Japan.,
Ichiro Matsuda - Department of Population and Family Health, Moi University, PO Box 4606, Eldoret 30100, Kenya.,
Duncan Ngare - National Human Genome Research Institute, National Institutes of Health, 5635 Fishers Lane Suite 3039, Bethesda, Maryland 20892, USA.,
Vivian Ota Wang - Department of Anthropology, University of Houston at Clear Lake, 2700 Bay Area Boulevard, PO Box 295, Houston, Texas 77058-1098, USA.,
Deepa Reddy - National Human Genome Research Institute, Center for Research on Genomics and Global Health, 12 South Drive, MSC 5635, Building 12A, Room 4047, Bethesda, Maryland 20892-5635, USA.,
Charles N. Rotimi - Duke University, Institute for Genome Sciences and Policy, 450 Research Drive, PO Box 91009, LSRC B-Wing, Room 320B, Durham, North Carolina 27708, USA.,
Charmaine D. Royal - Department of Bioethics, The Cleveland Clinic, 9500 Euclid Avenue JJ60, Cleveland, Ohio 44124, USA.,
Richard R. Sharp - Beijing Institute of Genomics, Chinese Academy of Science, Beijing Airport Industrial Zone B-6, Beijing 101300, China.,
Changqing Zeng - National Human Genome Research Institute, National Institutes of Health, 5635 Fishers Lane Suite 4076, Bethesda, Maryland 20892, USA ,
Lisa D. Brooks & Jean E. McEwen
Consortia
The International HapMap 3 Consortium
Principal investigators
- David M. Altshuler
- , Richard A. Gibbs
- & Leena Peltonen
Project coordination leaders
- David M. Altshuler
- , Richard A. Gibbs
- , Leena Peltonen
- & Emmanouil Dermitzakis
Manuscript writing group
- Stephen F. Schaffner
- , Fuli Yu
- , Leena Peltonen
- , Emmanouil Dermitzakis
- , Penelope E. Bonnen
- , David M. Altshuler
- , Richard A. Gibbs
Genotyping and QC
* Paul I. W. de Bakker (Co-leader) * , Panos Deloukas (Co-leader) * , Stacey B. Gabriel * , Rhian Gwilliam * , Sarah Hunt * , Michael Inouye (Co-leader) * , Xiaoming Jia * , Aarno Palotie * , Melissa Parkin (Co-leader) * & Pamela Whittaker
ENCODE 3 sequencing and SNP discovery
* Fuli Yu (Leader) * , Kyle Chang * , Alicia Hawes * , Lora R. Lewis * , Yanru Ren * , David Wheeler * , Richard A. Gibbs * & Donna Marie Muzny
Copy number variation typing and analysis
* Chris Barnes * , Katayoon Darvishi * , Matthew Hurles (Co-leader) * , Joshua M. Korn * , Kati Kristiansson * , Charles Lee * , Steven A. McCarroll (Co-leader) * & James Nemesh
Population analysis
* Emmanouil Dermitzakis * , Alon Keinan (Leader) * , Stephen B. Montgomery * , Samuela Pollack * , Alkes L. Price * & Nicole Soranzo
Low frequency variation analysis
* Penelope E. Bonnen * , Richard A. Gibbs * , Claudia Gonzaga-Jauregui * , Alon Keinan * , Alkes L. Price * & Fuli Yu (Leader)
Linkage disequilibrium and haplotype sharing analysis
* Verneri Anttila * , Wendy Brodeur * , Mark J. Daly * , Stephen Leslie * , Gil McVean * , Loukas Moutsianas * , Huy Nguyen * , Stephen F. Schaffner (Leader) * & Qingrun Zhang
Imputation
* Mohammed J. R. Ghori * , Ralph McGinnis (Co-leader) * , William McLaren * , Samuela Pollack * , Alkes L. Price (Co-leader) * , Stephen F. Schaffner (Co-leader) * & Fumihiko Takeuchi
Natural selection
* Sharon R. Grossman * , Ilya Shlyakhter * , Elizabeth B. Hostetter * & Pardis C. Sabeti (Leader)
Community engagement and sample collection groups
* 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
Scientific management
* Lisa D. Brooks * & Jean E. McEwen
Corresponding authors
Correspondence toDavid M. Altshuler, Richard A. Gibbs, David M. Altshuler, Richard A. Gibbs, David M. Altshuler, Richard A. Gibbs, Richard A. Gibbs or Richard A. Gibbs.
Ethics declarations
Competing interests
The author declare no competing financial interests.
Additional information
The HapMap 3/ENCODE 3 data set has been deposited at http://www.hapmap.org. The sequence traces of ENCODE 3 can be accessed at http://www.ncbi.nlm.nih.gov/Traces/trace.cgi by submitting the query:species_code5“HOMO SAPIENS” and CENTER_NAME 5 “BCM” and CENTER_PROJECT 5 “RHIAY”.
A list of participants and their affiliations appears at the end of the paper
Supplementary information
Supplementary Information
This file contains Supplementary Information comprising Introduction, Large Scale Genotyping, Rare Allele Calling Bias, Deep PCR Sequencing, Copy Number Polymorphism (CNP) Analysis, Population Analyses, Recurrent SNPs and Haplotype sharing (see Contents page for full details). It also includes Supplementary Tables 1-11, Supplementary Figures 1-9 with legends and additional references. (PDF 1111 kb)
PowerPoint slides
Rights and permissions
About this article
Cite this article
The International HapMap 3 Consortium. Integrating common and rare genetic variation in diverse human populations.Nature 467, 52–58 (2010). https://doi.org/10.1038/nature09298
- Received: 10 November 2009
- Accepted: 21 June 2010
- Issue Date: 02 September 2010
- DOI: https://doi.org/10.1038/nature09298