Analysis of 6,515 exomes reveals the recent origin of most human protein-coding variants (original) (raw)

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Data deposits

Filtered sets of annotated variants and their allele frequencies are available at (http://evs.gs.washington.edu/EVS/) and genotypes and phenotypes from a large subset of individuals are also available through dbGaP (http://www.ncbi.nlm.nih.gov/gap) using the following accession information: NHLBI GO-ESP: Women’s Health Initiative Exome Sequencing Project (WHI) – WHISP, WHISP_Subject_Phenotypes, pht002246.v2.p2, phs000281.v2.p2; NHLBI GO-ESP: Heart Cohorts Exome Sequencing Project (JHS), ESP_HeartGO_JHS_LDLandEOMI_Subject_Phenotypes, pht002539.v1.p1, phs000402.v1.p1; NHLBI GO-ESP: Heart Cohorts Exome Sequencing Project (FHS), HeartGO_FHS_LDLandEOMI_PhenotypeDataFile, pht002476.v1.p1, phs000401.v1.p1; NHLBI GO-ESP: Heart Cohorts Exome Sequencing Project (CHS), HeartGO_CHS_LDL_PhenotypeDataFile, pht002536.v1.p1, phs000400.v1.p1; NHLBI GO-ESP: Heart Cohorts Exome Sequencing Project (ARIC), ESP_ARIC_LDLandEOMI_Sample, pht002466.v1.p1, phs000398.v1.p1;NHLBIGO-ESP: Lung Cohorts Exome Sequencing Project (Cystic Fibrosis), ESP_LungGO_CF_PA_Culture_Data, pht002227.v1.p1, phs000254.v1.p1; NHLBI GO-ESP: Early-Onset Myocardial Infarction (Broad EOMI), ESP_Broad_EOMI_Subject_Phenotypes, pht001437.v1.p1, phs000279.v1.p1; NHLBI GO-ESP: Lung Cohorts Exome Sequencing Project (Pulmonary Arterial Hypertension), PAH_Subject_Phenotypes_Baseline_Measures, pht002277.v1.p1, phs000290.v1.p1; NHLBI GO-ESP: Lung Cohorts Exome Sequencing Project (Lung Health Study of Chronic Obstructive Pulmonary Disease), LHS_COPD_Subject_Phenotypes_Baseline_Measures, pht002272.v1.p1, phs000291.v1.p1.

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Acknowledgements

We acknowledge the support of the National Heart, Lung and Blood Institute (NHLBI), the contributions of the research institutions that participated in this study, the study investigators, field staff and study participants who created this resource for biomedical research, and the Population Genetics Project Team of the NHLBI. We thank J. Wilson and R. Do for critical feedback on the manuscript. Funding for the GO (Grand Opportunity) Exome Sequencing Project was provided by NHLBI grants RC2 HL-103010 (Heart GO), RC2 HL-102923 (Lung GO) and RC2 HL-102924 (WHISP). The exome sequencing was was supported by NHLBI grants RC2 HL-102925 (Broad GO) and RC2 HL-102926 (Seattle GO).

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Authors and Affiliations

1. Department of Genome Sciences, University of Washington, Seattle, 98195, Washington, USA
   Wenqing Fu, Timothy D. O’Connor, Mark J. Rieder, Jay Shendure, Deborah A. Nickerson, Michael J. Bamshad & Joshua M. Akey
2. Department of Biostatistics, University of Michigan, Ann Arbor, 48109, Michigan, USA
   Goo Jun, Hyun Min Kang & Goncalo Abecasis
3. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, 77030, Texas, USA
   Suzanne M. Leal
4. Broad Institute of MIT and Harvard, Cambridge, 02142, Massachusetts, USA
   Stacey Gabriel & David Altshuler
5. Department of Pediatrics, University of Washington, Seattle, 98195, Washington, USA
   Michael J. Bamshad
6. *Lists of participants and affiliations appear in the Supplementary Information,
   NHLBI Exome Sequencing Project

Authors

1. Wenqing Fu
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2. Timothy D. O’Connor
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3. Goo Jun
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4. Hyun Min Kang
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5. Goncalo Abecasis
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6. Suzanne M. Leal
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7. Stacey Gabriel
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8. Mark J. Rieder
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9. David Altshuler
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10. Jay Shendure
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11. Deborah A. Nickerson
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12. Michael J. Bamshad
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13. NHLBI Exome Sequencing Project
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14. Joshua M. Akey
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Contributions

W.F. and J.M.A. conceived the analyses. D.A.N., S.G., M.J.R. and D.A. oversaw data generation and quality control. G.J., H.M.K. and G.A. developed algorithms and identified SNVs from the sequencing data. W.F. carried out the majority of analyses with contributions from T.D.O. W.F., M.J.B., J.S. and J.M.A. analysed the data and wrote the manuscript with contributions from all authors. W.F., T.D.O., S.M.L., J.S., M.J.R., D.A.N., M.J.B. and J.M.A. are members of the Seattle Grand Opportunity (GO) group and G.J., H.M.K., G.A., S.G. and D.A. are members of the Broad GO group, which are both sub-groups of the NHLBI Exome Sequencing Project (ESP).

Corresponding authors

Correspondence toWenqing Fu or Joshua M. Akey.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Information

This file contains Supplementary Text and Data, Supplementary References, Supplementary Tables 1-4 and Supplementary Figures 1-15 (see Table of Contents for more details). (PDF 3066 kb)

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Fu, W., O’Connor, T., Jun, G. et al. Analysis of 6,515 exomes reveals the recent origin of most human protein-coding variants.Nature 493, 216–220 (2013). https://doi.org/10.1038/nature11690

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• Received: 13 July 2012
• Accepted: 19 October 2012
• Published: 28 November 2012
• Issue Date: 10 January 2013
• DOI: https://doi.org/10.1038/nature11690