Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Analysis of protein-coding genetic variation in 60,706 humans

Exome Aggregation Consortium, Monkol Lek, Konrad J Karczewski, Eric V Minikel, Kaitlin E Samocha, Eric Banks, Timothy Fennell, Anne H O’Donnell-Luria, James S Ware, Andrew J Hill, Beryl B Cummings, Taru Tukiainen, Daniel P Birnbaum, Jack A Kosmicki, Laramie Duncan, Karol Estrada, Fengmei Zhao, James Zou, Emma Pierce-Hoffman, David N Cooper, Mark DePristo, Ron Do, Jason Flannick, Menachem Fromer, Laura Gauthier, Jackie Goldstein, Namrata Gupta, Daniel Howrigan, Adam Kiezun, Mitja I Kurki, Ami Levy Moonshine, Pradeep Natarajan, Lorena Orozco, Gina M Peloso, Ryan Poplin, Manuel A Rivas, Valentin Ruano-Rubio, Douglas M Ruderfer, Khalid Shakir, Peter D Stenson, Christine Stevens, Brett P Thomas, Grace Tiao, Maria T Tusie-Luna, Ben Weisburd, Hong-Hee Won, Dongmei Yu, David M Altshuler, Diego Ardissino, Michael Boehnke, John Danesh, Roberto Elosua, Jose C Florez, Stacey B Gabriel, Gad Getz, Christina M Hultman, Sekar Kathiresan, Markku Laakso, Steven McCarroll, Mark I McCarthy, Dermot McGovern, Ruth McPherson, Benjamin M Neale, Aarno Palotie, Shaun M Purcell, Danish Saleheen, Jeremiah Scharf, Pamela Sklar, Patrick F Sullivan, Jaakko Tuomilehto, Hugh C Watkins, James G Wilson, Mark J Daly, Daniel G MacArthur
doi: https://doi.org/10.1101/030338
1Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA
Monkol Lek
1Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA
2Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA
3School of Paediatrics and Child Health, University of Sydney, Sydney, NSW, Australia
4Institute for Neuroscience and Muscle Research, Childrens Hospital at Westmead, Sydney, NSW, Australia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Konrad J Karczewski
1Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA
2Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Eric V Minikel
1Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA
2Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA
5Program in Biological and Biomedical Sciences, Harvard Medical School, Boston, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kaitlin E Samocha
1Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA
2Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA
6Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA
5Program in Biological and Biomedical Sciences, Harvard Medical School, Boston, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Eric Banks
2Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Timothy Fennell
2Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Anne H O’Donnell-Luria
1Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA
2Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA
7Division of Genetics and Genomics, Boston Children’s Hospital, Boston, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
James S Ware
2Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA
8Department of Genetics, Harvard Medical School, Boston, MA, USA
9National Heart and Lung Institute, Imperial College London, London, UK
10NIHR Royal Brompton Cardiovascular Biomedical Research Unit, Royal Brompton Hospital, London, UK
11MRC Clinical Sciences Centre, Imperial College London, London, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Andrew J Hill
1Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA
2Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA
12Genome Sciences, University of Washington, Seattle, WA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Beryl B Cummings
1Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA
2Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA
5Program in Biological and Biomedical Sciences, Harvard Medical School, Boston, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Taru Tukiainen
1Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA
2Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Daniel P Birnbaum
2Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jack A Kosmicki
1Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA
2Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA
6Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA
13Program in Bioinformatics and Integrative Genomics, Harvard Medical School, Boston, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Laramie Duncan
1Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA
2Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Karol Estrada
1Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA
2Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Fengmei Zhao
1Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA
2Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
James Zou
2Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Emma Pierce-Hoffman
1Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA
2Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
David N Cooper
14Institute of Medical Genetics, Cardiff University, Cardiff, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mark DePristo
15Broad Institute of MIT and Harvard, Cambridge, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ron Do
16Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA
17Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
18The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
19The Center for Statistical Genetics, Icahn School of Medicine at Mount Sinai, New York, NY, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jason Flannick
2Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA
20Department of Molecular Biology, Massachusetts General Hospital, Boston, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Menachem Fromer
1Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA
6Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA
21Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA
16Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA
17Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Laura Gauthier
15Broad Institute of MIT and Harvard, Cambridge, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jackie Goldstein
1Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA
2Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA
6Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Namrata Gupta
2Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Daniel Howrigan
1Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA
2Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA
6Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Adam Kiezun
15Broad Institute of MIT and Harvard, Cambridge, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mitja I Kurki
2Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA
22Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ami Levy Moonshine
15Broad Institute of MIT and Harvard, Cambridge, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Pradeep Natarajan
2Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA
23Harvard Medical School, Boston, MA, USA
24Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USA
25Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Lorena Orozco
26Immunogenomics and Metabolic Disease Laboratory, Instituto Nacional de Medicina Genomica, Mexico City, Mexico
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Gina M Peloso
2Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA
24Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USA
25Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ryan Poplin
15Broad Institute of MIT and Harvard, Cambridge, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Manuel A Rivas
2Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Valentin Ruano-Rubio
15Broad Institute of MIT and Harvard, Cambridge, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Douglas M Ruderfer
21Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA
16Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA
17Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Khalid Shakir
15Broad Institute of MIT and Harvard, Cambridge, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Peter D Stenson
14Institute of Medical Genetics, Cardiff University, Cardiff, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Christine Stevens
2Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Brett P Thomas
1Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA
2Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Grace Tiao
15Broad Institute of MIT and Harvard, Cambridge, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Maria T Tusie-Luna
27Department of Endocrinology and Metabolism, Instituto Nacional de Ciencias Medicas y Nutricion, Mexico City, Mexico
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ben Weisburd
2Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hong-Hee Won
2Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA
23Harvard Medical School, Boston, MA, USA
24Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USA
25Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Dongmei Yu
22Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston, MA, USA
28Department of Neurology, Brigham and Women’s Hospital, Boston, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
David M Altshuler
2Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA
29Vertex Pharmaceuticals, Boston, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Diego Ardissino
30Department of Cardiology, University Hospital, Parma, Italy
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Michael Boehnke
31Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
John Danesh
32Department of Public Health and Primary Care, Strangeways Research Laboratory, Cambridge, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Roberto Elosua
33Cardiovascular Epidemiology and Genetics, Hospital del Mar Medical Research Institute, Barcelona, Spain
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jose C Florez
2Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA
23Harvard Medical School, Boston, MA, USA
24Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Stacey B Gabriel
2Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Gad Getz
15Broad Institute of MIT and Harvard, Cambridge, MA, USA
23Harvard Medical School, Boston, MA, USA
34Department of Pathology and Cancer Center, Massachusetts General Hospital, Boston, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Christina M Hultman
35Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sekar Kathiresan
2Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA
23Harvard Medical School, Boston, MA, USA
24Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USA
25Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Markku Laakso
36Department of Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Steven McCarroll
6Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA
8Department of Genetics, Harvard Medical School, Boston, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mark I McCarthy
37Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK
38Oxford Centre for Diabetes,Endocrinology and Metabolism, University of Oxford, Oxford, UK
39Oxford NIHR Biomedical Research Centre, Oxford University Hospitals Foundation Trust, Oxford, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Dermot McGovern
40Inflammatory Bowel Disease and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ruth McPherson
41Atherogenomics Laboratory, University of Ottawa Heart Institute, Ottawa, ON, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Benjamin M Neale
1Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA
2Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA
6Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Aarno Palotie
42Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Shaun M Purcell
21Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA
16Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA
17Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Danish Saleheen
43Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA
44Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA
45Center for Non-Communicable Diseases, Karachi, Pakistan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jeremiah Scharf
22Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston, MA, USA
28Department of Neurology, Brigham and Women’s Hospital, Boston, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Pamela Sklar
21Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA
16Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA
17Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
46Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
47Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Patrick F Sullivan
48Department of Genetics, University of North Carolina, Chapel Hill, NC, USA
49Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jaakko Tuomilehto
50Department of Public Health, University of Helsinki, Helsinki, Finland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hugh C Watkins
51Radcliffe Department of Medicine, University of Oxford, Oxford, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
James G Wilson
52Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mark J Daly
1Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA
2Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA
6Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Daniel G MacArthur
1Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA
2Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

Summary

Large-scale reference data sets of human genetic variation are critical for the medical and functional interpretation of DNA sequence changes. Here we describe the aggregation and analysis of high-quality exome (protein-coding region) sequence data for 60,706 individuals of diverse ethnicities. The resulting catalogue of human genetic diversity has unprecedented resolution, with an average of one variant every eight bases of coding sequence and the presence of widespread mutational recurrence. The deep catalogue of variation provided by the Exome Aggregation Consortium (ExAC) can be used to calculate objective metrics of pathogenicity for sequence variants, and to identify genes subject to strong selection against various classes of mutation; we identify 3,230 genes with near-complete depletion of truncating variants, 79% of which have no currently established human disease phenotype. Finally, we show that these data can be used for the efficient filtering of candidate disease-causing variants, and for the discovery of human “knockout” variants in protein-coding genes.

Footnotes

  • ↵# List of collaborators to appear in Supplementary

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-ND 4.0 International license.
Back to top
PreviousNext
Posted October 30, 2015.
Download PDF

Supplementary Material

Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Analysis of protein-coding genetic variation in 60,706 humans
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Analysis of protein-coding genetic variation in 60,706 humans
Exome Aggregation Consortium, Monkol Lek, Konrad J Karczewski, Eric V Minikel, Kaitlin E Samocha, Eric Banks, Timothy Fennell, Anne H O’Donnell-Luria, James S Ware, Andrew J Hill, Beryl B Cummings, Taru Tukiainen, Daniel P Birnbaum, Jack A Kosmicki, Laramie Duncan, Karol Estrada, Fengmei Zhao, James Zou, Emma Pierce-Hoffman, David N Cooper, Mark DePristo, Ron Do, Jason Flannick, Menachem Fromer, Laura Gauthier, Jackie Goldstein, Namrata Gupta, Daniel Howrigan, Adam Kiezun, Mitja I Kurki, Ami Levy Moonshine, Pradeep Natarajan, Lorena Orozco, Gina M Peloso, Ryan Poplin, Manuel A Rivas, Valentin Ruano-Rubio, Douglas M Ruderfer, Khalid Shakir, Peter D Stenson, Christine Stevens, Brett P Thomas, Grace Tiao, Maria T Tusie-Luna, Ben Weisburd, Hong-Hee Won, Dongmei Yu, David M Altshuler, Diego Ardissino, Michael Boehnke, John Danesh, Roberto Elosua, Jose C Florez, Stacey B Gabriel, Gad Getz, Christina M Hultman, Sekar Kathiresan, Markku Laakso, Steven McCarroll, Mark I McCarthy, Dermot McGovern, Ruth McPherson, Benjamin M Neale, Aarno Palotie, Shaun M Purcell, Danish Saleheen, Jeremiah Scharf, Pamela Sklar, Patrick F Sullivan, Jaakko Tuomilehto, Hugh C Watkins, James G Wilson, Mark J Daly, Daniel G MacArthur
bioRxiv 030338; doi: https://doi.org/10.1101/030338
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
Analysis of protein-coding genetic variation in 60,706 humans
Exome Aggregation Consortium, Monkol Lek, Konrad J Karczewski, Eric V Minikel, Kaitlin E Samocha, Eric Banks, Timothy Fennell, Anne H O’Donnell-Luria, James S Ware, Andrew J Hill, Beryl B Cummings, Taru Tukiainen, Daniel P Birnbaum, Jack A Kosmicki, Laramie Duncan, Karol Estrada, Fengmei Zhao, James Zou, Emma Pierce-Hoffman, David N Cooper, Mark DePristo, Ron Do, Jason Flannick, Menachem Fromer, Laura Gauthier, Jackie Goldstein, Namrata Gupta, Daniel Howrigan, Adam Kiezun, Mitja I Kurki, Ami Levy Moonshine, Pradeep Natarajan, Lorena Orozco, Gina M Peloso, Ryan Poplin, Manuel A Rivas, Valentin Ruano-Rubio, Douglas M Ruderfer, Khalid Shakir, Peter D Stenson, Christine Stevens, Brett P Thomas, Grace Tiao, Maria T Tusie-Luna, Ben Weisburd, Hong-Hee Won, Dongmei Yu, David M Altshuler, Diego Ardissino, Michael Boehnke, John Danesh, Roberto Elosua, Jose C Florez, Stacey B Gabriel, Gad Getz, Christina M Hultman, Sekar Kathiresan, Markku Laakso, Steven McCarroll, Mark I McCarthy, Dermot McGovern, Ruth McPherson, Benjamin M Neale, Aarno Palotie, Shaun M Purcell, Danish Saleheen, Jeremiah Scharf, Pamela Sklar, Patrick F Sullivan, Jaakko Tuomilehto, Hugh C Watkins, James G Wilson, Mark J Daly, Daniel G MacArthur
bioRxiv 030338; doi: https://doi.org/10.1101/030338

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Genomics
Subject Areas
All Articles
  • Animal Behavior and Cognition (4113)
  • Biochemistry (8815)
  • Bioengineering (6518)
  • Bioinformatics (23460)
  • Biophysics (11789)
  • Cancer Biology (9207)
  • Cell Biology (13322)
  • Clinical Trials (138)
  • Developmental Biology (7436)
  • Ecology (11409)
  • Epidemiology (2066)
  • Evolutionary Biology (15150)
  • Genetics (10436)
  • Genomics (14043)
  • Immunology (9171)
  • Microbiology (22153)
  • Molecular Biology (8812)
  • Neuroscience (47567)
  • Paleontology (350)
  • Pathology (1428)
  • Pharmacology and Toxicology (2491)
  • Physiology (3730)
  • Plant Biology (8079)
  • Scientific Communication and Education (1437)
  • Synthetic Biology (2221)
  • Systems Biology (6037)
  • Zoology (1253)