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Regional missense constraint improves variant deleteriousness prediction

Kaitlin E. Samocha, Jack A. Kosmicki, Konrad J. Karczewski, Anne H. O’Donnell-Luria, Emma Pierce-Hoffman, Daniel G. MacArthur, Benjamin M. Neale, Mark J. Daly
doi: https://doi.org/10.1101/148353
Kaitlin E. Samocha
1Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
2Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
3Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
4Program in Genetics and Genomics, Biological and Biomedical Sciences, Harvard Medical School, Boston, Massachusetts, USA.
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Jack A. Kosmicki
1Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
2Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
3Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
5Program in Bioinformatics and Integrative Genomics, Harvard University, Cambridge, Massachusetts, USA.
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Konrad J. Karczewski
1Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
2Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
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Anne H. O’Donnell-Luria
1Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
2Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
6Division of Genetics and Genomics, Boston Children’s Hospital, Boston, Massachusetts, USA.
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Emma Pierce-Hoffman
1Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
2Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
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Daniel G. MacArthur
1Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
2Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
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Benjamin M. Neale
1Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
2Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
3Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
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Mark J. Daly
1Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
2Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
3Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
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  • For correspondence: mjdaly@atgu.mgh.harvard.edu
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Article Information

doi 
https://doi.org/10.1101/148353
History 
  • June 12, 2017.
Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.

Author Information

  1. Kaitlin E. Samocha1,2,3,4,
  2. Jack A. Kosmicki1,2,3,5,
  3. Konrad J. Karczewski1,2,
  4. Anne H. O’Donnell-Luria1,2,6,
  5. Emma Pierce-Hoffman1,2,
  6. Daniel G. MacArthur1,2,
  7. Benjamin M. Neale1,2,3 and
  8. Mark J. Daly1,2,3,*
  1. 1Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
  2. 2Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
  3. 3Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
  4. 4Program in Genetics and Genomics, Biological and Biomedical Sciences, Harvard Medical School, Boston, Massachusetts, USA.
  5. 5Program in Bioinformatics and Integrative Genomics, Harvard University, Cambridge, Massachusetts, USA.
  6. 6Division of Genetics and Genomics, Boston Children’s Hospital, Boston, Massachusetts, USA.
  1. ↵* Correspondence to: mjdaly{at}atgu.mgh.harvard.edu
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Posted June 12, 2017.
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Regional missense constraint improves variant deleteriousness prediction
Kaitlin E. Samocha, Jack A. Kosmicki, Konrad J. Karczewski, Anne H. O’Donnell-Luria, Emma Pierce-Hoffman, Daniel G. MacArthur, Benjamin M. Neale, Mark J. Daly
bioRxiv 148353; doi: https://doi.org/10.1101/148353
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Regional missense constraint improves variant deleteriousness prediction
Kaitlin E. Samocha, Jack A. Kosmicki, Konrad J. Karczewski, Anne H. O’Donnell-Luria, Emma Pierce-Hoffman, Daniel G. MacArthur, Benjamin M. Neale, Mark J. Daly
bioRxiv 148353; doi: https://doi.org/10.1101/148353

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