Inherited genetic variation has a critical but as yet largely uncharacterized role in human disease. Here we report a public database of common variation in the human genome: more than one million single nucleotide polymorphisms (SNPs) for which accurate and complete genotypes have been obtained in 269 DNA samples from four populations, including ten 500-kilobase regions in which essentially all information about common DNA variation has been extracted. These data document the generality of recombination hotspots, a block-like structure of linkage disequilibrium and low haplotype diversity, leading to substantial correlations of SNPs with many of their neighbours. We show how the HapMap resource can guide the design and analysis of genetic association studies, shed light on structural variation and recombination, and identify loci that may have been subject to natural selection during human evolution.
Bibliographical noteFunding Information:
Acknowledgements We thank many people who contributed to this project: J. Beck, C. Beiswanger, D. Coppock, A. Leach, J. Mintzer and L. Toji (Coriell Institute for Medical Research) for transforming the Yoruba, Japanese and Han Chinese samples, distributing the DNA and cell lines, storing the samples for use in future research, and producing the community newsletters and reports; J. Greenberg and R. Anderson (NIH National Institute of General Medical Sciences) for providing funding and support for cell line transformation and storage in the NIGMS Human Genetic Cell Repository at the Coriell Institute; T. Dibling, T. Ishikura, S. Kanazawa, S. Mizusawa and S. Saito (SNP Research Center, RIKEN) for help with genotyping; C. Hind and A. Moghadam for technical support in genotyping and all members of the subcloning and sequencing teams at the Wellcome Trust Sanger Institute; X. Ke (Wellcome Trust Centre for Human Genetics at the University of Oxford) for help with data analysis; Oxford E-Science Centre for provision of high-performance computing resources; H. Chen, W. Chen, L. Deng, Y. Dong, C. Fu, L. Gao, H. Geng, J. Geng, M. He, H. Li, H. Li, S. Li, X. Li, B. Liu, Z. Liu, F. Lu, F. Lu, G. Lu, C. Luo, X. Wang, Z. Wang, C. Ye and X. Yu (Beijing Genomics Institute) for help with genotyping and sample collection; X. Feng, Y. Li, J. Ren and X. Zhou (Beijing Normal University) for help with sample collection; J. Fan, W. Gu, W. Guan, S. Hu, H. Jiang, R. Lei, Y. Lin, Z. Niu, B. Wang, L. Yang, W. Yang, Y. Wang, Z. Wang, S. Xu, W. Yan, H. Yang, W. Yuan, C. Zhang, J. Zhang, K. Zhang and G. Zhao (Chinese National Human Genome Center at Shanghai) for help with genotyping; P. Fong, C. Lai, C. Lau, T. Leung, L. Luk and W. Tong (University of Hong Kong, Genome Research Centre) for help with genotyping; C. Pang (Chinese University of Hong Kong) for help with genotyping; K. Ding, B. Qiang, J. Zhang, X. Zhang and K. Zhou (Chinese National Human Genome Center at Beijing) for help with genotyping; Q. Fu, S. Ghose, X. Lu, D. Nelson, A. Perez, S. Poole, R. Vega and H. Yonath (Baylor College of Medicine); C. Bruckner, T. Brundage, S. Chow, O. Iartchouk, M. Jain, M. Moorhead and K. Tran (ParAllele Bioscience Inc.); N. Addleman, J. Atilano, T. Chan, C. Chu, C. Ha, T. Nguyen, M. Minton and A. Phong (UCSF) for help with genotyping, and D. Lind (UCSF) for help with quality control and experimental design; R. Donaldson and S. Duan (Washington University) for help with genotyping, and J. Rice and N. Saccone (Washington University) for help with experimental design; J. Wigginton (University of Michigan) for help with implementing and testing QA/QC software; A. Clark, B. Keats, R. Myers, D. Nickerson and A. Williamson for providing advice to NIH; J. Melone, M. Weiss and E. DeHaut-Combs (NHGRI) for help with project management; M. Gray for organizing phone calls and meetings; D. Leja for help with figures; the Yoruba people of Ibadan, Nigeria, the people of Tokyo, Japan, and the community at Beijing Normal University, who participated in public consultations and community engagements; the people in these communities who were generous in donating their blood samples; and the people in the Utah CEPH community who allowed the samples they donated earlier to be used for the Project. We also thank A. Clark, E. Lander, C. Langley and R. Lifton for comments on earlier drafts of the manuscript. This work was supported by the Japanese Ministry of Education, Culture, Sports, Science, and Technology, the Wellcome Trust, Nuffield Trust, Wolfson Foundation, UK EPSRC, Genome Canada, Génome Québec, the Chinese Academy of Sciences, the Ministry of Science and Technology of the People’s Republic of China, the National Natural Science Foundation of China, the Hong Kong Innovation and Technology Commission, the University Grants Committee of Hong Kong, the SNP Consortium, the US National Institutes of Health (FIC, NCI, NCRR, NEI, NHGRI, NIA, NIAAA, NIAID, NIAMS, NIBIB, NIDA, NIDCD, NIDCR, NIDDK, NIEHS, NIGMS, NIMH, NINDS, NLM, OD), the W.M. Keck Foundation, and the Delores Dore Eccles Foundation.