Analysis of protein-coding genetic variation in 60,706 humans
Creators: name: Atzmon, 
name: Palotie, Aarno
name: Ripke, 
name: Rivas, Manuel A.
name: Won, Hong-Hee
name: Freimer, 
name: Lyon, 
name: Rodríguez-Guillén, 
name: Barr, 
name: Weisburd, Ben
name: Neale, Benjamin M.
name: Sklar, Pamela
name: Yu, Dongmei
name: Fontanillas, 
name: Riba, 
name: Samocha, Kaitlin E.
name: Kähler, 
name: Meigs, 
name: Tsuang, Ming T.
name: González-Villalpando, 
name: Lehman, 
name: Sandor, 
name: Daly, Mark J.
name: Hanis, 
name: Thomas, Brett P.
name: Groop, 
name: Cox, 
name: Mahajan, 
name: Bergen, 
name: Sladek, 
name: King, 
name: Gabriel, Stacey B.
name: Huerta-Chagoya, 
name: Abboud, 
name: Ware, James S.
name: Flannick, Jason
name: Kyriakou, 
name: Tiao, Grace
name: Chambert, 
name: McPherson, Ruth
name: Kathiresan, Sekar
name: Teslovich, 
name: Haiman, 
name: Ruderfer, Douglas M.
name: Hopewell, 
name: Scharf, Jeremiah M.
name: Sullivan, Patrick F.
name: Getz, Gad
name: Ordóñez-Sánchez, 
name: Orozco, Lorena
name: Jiménez-Morale, 
name: Frayling, 
name: Mercader, 
name: Zou, James
name: Boehnke, Michael
name: Rose, Samuel A.
name: Burtt, 
name: Stevens, Christine
name: Moonshine, Ami Levy
name: Najmi, 
name: Tusie-Luna, Maria T.
name: Glatt, Stephen J.
name: Duggirala, 
name: Morris, 
name: Ruano-Rubio, Valentin
name: Laakso, Markku
name: Ardissino, Diego
name: Bell, 
name: Mohlke, 
name: Marrugat, 
name: Rodríguez-Torres, 
name: Tukiainen, Taru
name: Mendoza-Caamal, 
name: Stenson, Peter D.
name: Tai, 
name: Spector, 
name: MacArthur, Daniel G.
name: Goel, 
name: Lek, Monkol
name: Saleheen, Danish
name: O'Donnell-Luria, Anne H.
name: Moran, 
name: Duncan, Laramie E.
name: Fernandez-Lopez, 
name: McCarthy, Mark I.
name: Cummings, Beryl B.
name: Banks, Eric
name: Danesh, John
name: Kirov, 
name: Budman, 
name: Do, Ron
name: Fennell, Timothy
name: Gupta, Namrata
name: Poplin, Ryan
name: Kurki, Mitja I.
name: Bowden, 
name: Abecasis, 
name: Soberón, 
name: DePristo, Mark
name: García-Ortiz, 
name: Lee, 
name: Zhao, Fengmei
name: Meitinger, 
name: González-Villalpando, 
name: Centeno-Cruz, 
name: Kosmicki, Jack A.
name: Purcell, Shaun M.
name: Jenkinson, 
name: Hultman, Christina M.
name: Donnelly, Stacey
name: Watkins, Hugh C.
name: Howrigan, Daniel
name: Tuomilehto, Jaakko
name: Grados, 
name: MacMahon, 
name: Walford, 
name: Cortes, 
name: Berghout, Joanne
name: Natarajan, Pradeep
name: Estrada, Karol
name: Park, 
name: Pauls, 
name: Njølstad, 
name: Arellano-Campos, 
name: Kiezun, Adam
name: Florez, Jose C.
name: Posthuma, 
name: McGovern, Dermot
name: Altshuler, David M.
name: Fuchsberger, 
name: Revilla-Monsalve, 
name: Cooper, David N.
name: Wilson, James G.
name: Deflaux, Nicole
name: Williams, 
name: Islas-Andrade, 
name: Coppola, 
name: Farrall, 
name: McVean, 
name: Birnbaum, Daniel P.
name: Gauthier, Laura
name: Karczewski, Konrad J.
name: Clarke, 
name: O'Donovan, 
name: Córdova, 
name: Aukrust, 
name: Seielstad, 
name: Jalilzadeh, 
name: Kooner, 
name: Fromer, Menachem
name: Minikel, Eric V.
name: Goldstein, Jackie
name: Collins, 
name: Aguilar-Salinas, 
name: Henderson, 
name: Jacobs, 
name: McCarroll, Steven
name: Hattersley, 
name: Magnusson, 
name: Pierce-Hoffman, Emma
name: Gómez-Vázquez, 
name: Wilkens, 
name: Moreno-Macías, 
name: Mathews, 
name: Elosua, Roberto
name: Martínez-Hernández, 
name: Hill, Andrew J.
name: Blangero, 
name: Peloso, Gina M.
name: Shakir, Khalid
name: Owen, 
name: Bjørkhaug, 
name: Chambers, 
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2016

description: Large-scale reference data sets of human genetic variation are critical for the medical and functional interpretation of DNA sequence changes. We describe the aggregation and analysis of high-quality exome (protein-coding region) sequence data for 60,706 individuals of diverse ethnicities generated as part of the Exome Aggregation Consortium (ExAC). This catalogue of human genetic diversity contains an average of one variant every eight bases of the exome, and provides direct evidence for the presence of widespread mutational recurrence. We have used this catalogue to calculate objective metrics of pathogenicity for sequence variants, and to identify genes subject to strong selection against various classes of mutation; identifying 3,230 genes with near-complete depletion of truncating variants with 72% having no currently established human disease phenotype. Finally, we demonstrate 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.