De novo mutations across 1,465 diverse genomes reveal mutational insights and reductions in the Amish founder population

著者: Michael D. Kessler, Douglas P. Loesch, James A. Perry, Nancy L. Heard‐Costa, Daniel Taliun, Brian E. Cade, Heming Wang, Michelle Daya, John Ziniti, Soma Datta, Juan C. Celedón, Manuel E. Soto-Quirós, Lydiana Ávila, Scott T. Weiss, Kathleen C. Barnes, Susan Redline, Ramachandran S. Vasan, Andrew D. Johnson, Rasika A. Mathias, Ryan D. Hernandez, James G. Wilson, Deborah A. Nickerson, Gonçalo R. Abecasis, Sharon R. Browning, Sebastian Zöllner, Jeffrey R. O’Connell, Braxton D. Mitchell, TOPMed Population Genetics Working Group, Timothy D. O’Connor, Sanne E. Aalbers, Moustafa Abdalla, Omar Abdul‐Rahman, Gonçalo R. Abecasis, Avinash Abhyankar, Indra Adrianto, François Aguet, Rachel Akers, Rafet Al-Tobasei, Christine M. Albert, Micheala A. Aldred, Laura Almasy, Márcio Rodrigues de Almeida, Álvaro Alonso, Seth A. Ament, Elizabeth Ampleford, Ping An, Christopher D. Anderson, Charlotte Andersson, Pramod Anugu, Elizabeth L. Appelbaum, Kristin Ardlie, Dan Arking, Sebastian M. Armasu, Donna K. Arnett, Heather T Arruda, Marios Arvanitis, Allison E. Ashley‐Koch, Aneel A. Ashrani, Stella Aslibekyan, Tim Assimes, Elizabeth J. Atkinson, Paul L. Auer, Thomas R. Austin, Christy L. Avery, Julián Ávila-Pacheco, Paul Avillach, Abraham Aviv, Dimitrios Avramopoulos, Christie M. Ballantyne, Pallavi Balte, Michael J. Bamshad, Mike Bancks, John Barnard, Kathleen C. Barnes, R. Graham Barr, Emily Barron‐Casella, Traci M. Bartz, Lucas Barwick, Saonli Basu, Alexis Battle, Michaël Baumann, David Beame, Terri Beaty, Gerald J. Beck, Lewis C. Becker, Diane M. Becker, Rebecca Beer, Ferdouse Begum, Alexa Beiser, Amber L. Beitelshees, Emelia J. Benjamin, Takis Benos, Hanna Berk-Rauch, Zachary M Besich, Marcos Bezerra, Surya P. Bhatt, Wenjian Bi, Alexander G. Bick, Larry Bielak, Mary L. Biggs, Joshua C. Bis, Thomas W. Blackwell, John Blangero, Eugene Bleecker, Brandon M. Blobner, Toby Bloom, Elizabeth Blue, Corneliu Bodea, Mike Boehnke, Eric Boerwinkle, Sílvia Bonàs‐Guarch, Donald W. Bowden, Michael Bowers, Russell P. Bowler, Jan Bressler, Jennifer A. Brody, Ulrich Broeckel, Jai Broome, Matthew Brown, Michael Brown, Brian L. Browning, Sharon R. Browning, Joseph L. Bundy, Esteban G. Burchard, Robert D. Burk, Carlos D. Bustamante, Erin Buth, Javed Butler, Brian E. Cade, Jonathan Cardwell, Vincent J. Carey, Jenna C. Carlson, Cara L. Carty, Richard Casaburi, James F. Casella, Peter J. Castaldi, Mark Chaffin, Jin Choul Chai, Aravinda Chakravarti, Lavanya Challagundla, Nathalie Chami, Kei Hang, Katie Chan, I-Shou Chang, Christy Chang, Yi‐Cheng Chang, Sinéad B. Chapman, Daniel I. Chasman, Sameer Chavan Yii-Der, Ida Chen, Wei‐Min Chen, Zhanghua Chen, Han Chen, Fang Chen, Shu Hui Chen, Ming‐Huei Chen, Chen Ye, Susan Cheng, Yen‐Feng Chiu, Michael Cho, Seung Hoan Choi, Zechen Chong, Jessica X. Chong, Ingrid E. Christophersen, Audrey Y. Chu, Shih‐Kai Chu, Lee‐Ming Chuang, Sung Chun, Jaeyoon Chung, Mina K. Chung, Ren‐Hua Chung, Mina Cintho, Ozahata Mete Civelek, Steven A. Claas, Robert Clark, Shoa L. Clarke, Melina Claussnitzer, Jean R. Clemenceau, Clary B. Clish, Sean Coady, Bradley P. Coe, John W. Cole, Suzy Comhair, Matthew P. Conomos, Brandon J. Coombes, Matthew G. Cordes, Laura Corlin, Elaine Cornell, Adolfo Correa, André Corvelo, Paul Courchesne, Laura Courtney, Carolyn Crandall, James D. Crapo, Damien C. Croteau‐Chonka, Pedro Cruz, L. Adrienne Cupples, Joanne E. Curran, Jeffrey L. Curtis, Brian Custer, Michael J. Cutler, Coleen Damcott, Scott M. Damrauer, Dawood Darbar, Sean P. David, Warwick Daw, Michelle Daya, Mariza de Andrade, Paul S. de Vries, Michael R. DeBaun, Christopher R. deFilippi, Ranjan Deka, Chris Delaney, Tracie DeLuca, Dawn L. DeMeo, Serkalem Demissie, Xutao Deng, Vimal K. Derebail, Pinkal Desai, Anita L. DeStefano, Scott E. Devine, Daniel DiCorpo, Carla Luana Dinardo, Jingzhong Ding, Jun Ding, Jasmin Divers, Avantika R. Diwadkar, Ron Do, HarshaVardhan Doddapaneni, Huawei Dong, Margaret Mengmeng Du, Qing Duan, Shannon Dugan‐Perez, Ravi Duggirala, Josée Dupuis, Jon Peter Durda, Susan K. Dutcher, Charles B. Eaton, Walter L. Eckalbar, Clara S. Ehrman, Evan E. Eichler, Lynette Ekunwe, Adel Boueiz, Jennifer R. Elhawary, Patrick T. Ellinor, Amanda Elliott, Connor A. Emdin, Leslie S. Emery, Mary J. Emond, Celeste Eng, Serpil C. Erzurum, Tõnu Esko, Luke M. Evans, Shaohua Fan, Fang Fang, Nauder Faraday, Charles R. Farber, David W. Fardo, Candace N. Farmer, Leanna Farnam, Diane Fatkin, Mary F. Feitosa, Adam L. Felsenfeld, Jean Feng, Mike Feolo, Lindsay Fernández‐Rhodes, Nicole M. Ferraro, Jorge Ferrer, Jessica L. Fetterman, Allison Fialkowski, Tasha E. Fingerlin, Annette L. Fitzpatrick, Jonathan M. Flanagan, Jason Flannick, Katherine Fleck, Matthew Flickinger, José C. Florez, James S. Floyd, Bernard Fongang, Marilyn G. Foreman, Myriam Fornage, Cassandra Foster, Caroline S. Fox, Ervin R. Fox, Nora Franceschini, Laurent C. Francioli, Alan J. Franklin, Chris Frazar, Amanda M. Fretts, Yi‐Ping Fu, Mao Fu, Stephanie M. Fullerton, Lucinda A. Fulton, Anna Furniss, Stacey Gabriel, Sarah A. Gagliano Taliun, Taliun Weiniu Gan, Santhi K. Ganesh, Andrea Ganna, Yan Gao, Melissa Garcia, Lori Garman, Michael Garrett, Melanie E. Garrett, N.C. Gassner, W. James Gauderman, Kyle J. Gaulton, Amadou Gaye, Sheila M. Gaynor, Brady Gaynor, Steven Gazal, Bruce D. Gelb, Xin Geng, Mark W. Geraci, Søren Germer, Robert E. Gerszten, Sina A. Gharib, Richard A. Gibbs, Lucas A. Gillenwater, Frank Gilliland, Mark T. Gladwin, David C. Glahn, Jennifer Godfrey, Ponce David Goff, Stephanie M. Gogarten, Rahul Gondalia, Da‐Wei Gong, Hector M. González, Mark O. Goodarzi, Matthew Goodman, Victor R. Gordeuk, Harald H.H. Göring, Daniel J. Gottlieb, Jérôme Goudet, Misa Graff, Jan Graffelman, Sarah E. Graham, Penelope E. Graves, Sharon Graw, Nancy Green, Kelsey Grinde, Michael Griswold, Megan L. Grove, C. Charles Gu, Weihua Guan, Hongsheng Gui, Xiuqing Guo, Namrata Gupta, María Gutiérrez‐Arcelus, Mary E. Haas, Jeff Haessler, Yang Hai, Cassie Hajek, Håkon Håkonarson, Lauren Hale, Michael E. Hall, Ira M. Hall, Amelia Weber Hall, Anne Hamik, Bob Handsaker, Sarah C. Hanks, Matthew E.B. Hansen, Manjit Hanspal, Luning Hao, Ross C. Hardison, Bernhard Haring, Kelley Harris, Daniel Harris, Natalie R. Hasbani, David Haussler, Nicola L. Hawley, Lystra P. Hayden, Kathleen M. Hayden, Jiang He, Karen He, Nancy L. Heard‐Costa, Ben Heavner, Susan R. Heckbert, Julian Hecker, Ryan Hernandez, Megan Herndon, David Herrington, Craig P. Hersh, Bertha Hidalgo, Heather M. Highland, Blanca E. Himes, Joel N. Hirschhorn, Marie‐France Hivert, James E. Hixson, Brian D. Hobbs, Chani J. Hodonsky, Chancellor Hohensee, John E. Hokanson, Charles C. Hong, Martha Horike‐Pyne, Steve Horvath, Karin F. Hoth, Lifang Hou, Candace M Howard-Claudio, Tzu‐Hung Hsiao, Chao A. Hsiung, Wan-Ling Nicole Hsu, Lucy L. Hsu, Yi‐Hsiang Hsu, Xiaowei Hu, Yao Hu, Tianxiao Huan, Jie Huang, Tianyi Huang, Benjamin Hubert, Jennifer E. Huffman, Timothy M. Hughes, Tae Hyun Hwang, Shih‐Jen Hwang, Chii Min Hwu, Hyacinth Hyacinth, Hae Kyung Im, Marguerite R. Irvin, Carmen R. Isasi, Yuval Itan, Kruthika Iyer, Rebecca Jackson, Deepti Jain, Sidd Jaiswal, Seon-Kyeong Jang, Cashell E. Jaquish, Gail P. Jarvik, Thomas Jaworek, Paul R. Jensen, Min A. Jhun, Xueqiu Jian, Jicai Jiang, Yu Jiang, Roby Joehanes, Eric Johanson, Jill M. Johnsen, Craig Johnson, Andrew D. Johnson, Rich Johnston, Michelle Jones, Kimberly Jones, Jaehyun Joo, Daniel M. Jordan, Kizer Jorge, Aparacio Jose, Brian Joyce, Renae Judy, Goo Jun, Anne E. Justice, Priyadarshini Kachroo, Ravi Kalhan, Jonathan R. Kaltman, Rita R. Kalyani, Kanika Kanchan, Hyun Min Kang, Divy Kangeyan, Robert C. Kaplan, David Karasik, Sharon Kardia, Silva Kasela, Sekar Kathiresan, Daniel H. Katz, Katerina Kechris, Addison Keely, Richard Keitch, Spencer T. Kelley, Rachel S. Kelly, Tanika N. Kelly, Shannon Kelly, Eimear E. Kenny, Ali R. Keramati, Michael D. Kessler, Bryan Kestenbaum, Kevin L. Keys, Alyna Khan, Amit V. Khera, Minjung Kho, Muin J. Khoury, Douglas P. Kiel, Ryan Kim, Woori Kim, Wonji Kim, Eric H. Kim, Eileen King, Gregory L. Kinney, Frederick Kinyua, Kamanu Krzysztof Kiryluk, Steven J. Kittner, Derek Klarin, Małgorzata Klauzińska, Erica L. Kleinbrink, Robert Klemmer, Stacey Knight, Emma Knowles, Darae Ko, Barbara A. Konkle, Charles Kooperberg, Anna Köttgen, Christina Kourkoulis, Aldi T. Kraja, Brian G. Kral, Holly Kramer, William E. Kraus, Michael Krause, Stephanie Krauter, Mohanraj Krishnan, Rajesh Kumar, Roy Kuraisa, Gulriz Kurban, Pui–Yan Kwok, Alain Laederach, Preeti Lakshman, Kumar Jacqueline Lane, John Lane, Christoph Lange, Ethan M. Lange, Leslie A. Lange, Tuuli Lappalainen, Caleb A. Lareau, Martin G. Larson, Katie Larsson, Edward Lau, Lenore Launer, Cathy C. Laurie, Cecelia Laurie, Marie Lauzon, Suzanne M. Leal, Meryl S. LeBoff, David J. Lederer, Wen‐Jane Lee, I‐Te Lee, Seunggeun Shawn Lee, Seung‐been Lee, Eunice Lee, Christina Lee, Jiwon Lee, Grace E. Lee, Dongwon Lee, Jonathon LeFaive, Rozenn N. Lemaître, Samantha Lent, Petra Lenzini, Aaron Leong, Guillaume Lettre, Albert M. Levin, David Levine, Dan Levy, Joshua P. Lewis, Yun Li, Huiqing Li, Xiaohui Li, Zilin Li, Xingnan Li, Xihao Li, Bingshan Li, Jingjing Liang, Elise Lim, Andrew H. Limper, Xihong Lin, Henry J. Lin, Honghuang Lin, D. Y. Lin, Bridget M. Lin, Amarise Little, Mengzhen Liu, Ching‐Ti Liu, Yongmei Liu, Yaowu Liu, Xiaoming Liu, Delong Liu, Dajiang J. Liu, Chunyu Liu, Q. Liu, Jingmin Liu, Simin Liu, Adam E. Locke, Douglas P. Loesch, Stephanie J. London, Michelle T. Long, Ryan J. Longchamps, W. T. Longstreth, Ruth J. F. Loos, Steven A. Lubitz, Kathryn L. Lunetta, Yang Luo, James Luo, Sharon M. Lutz, Yanlin Ma, Daniel G. MacArthur, Purnema Madahar, Anubha Mahajan, Michael C. Mahaney, J. G. Maher, Arch G. Mainous, Timothy D. Majarian, Angel C. Y. Mak, Rajeev Malhotra, Ani Manichaikul, Alisa K. Manning, JoAnn E. Manson, Sandro Marini, Lisa W. Martin, Fernando Martínez, Susan Mathai, Rasika A. Mathias, Susanne May, Richard Mayeux, Patrick F. McArdle, Steve McCarroll, Mark I. McCarthy, Merry‐Lynn McDonald, Barbara McDonough, Sean McFarland, Stephen T. McGarvey, Daniel McGoldrick, Daniel McGuire, Caitlin McHugh, Barbara McKnight, John C. McLenithan, David D. McManus, Tonya McSherry, Shannon L. Meeks, Hao Mei, James B. Meigs, Michael Mendelson, George A. Mensah, Josep M. Mercader, Tony R. Merriman, Geralyn Lambert‐Messerlian, Luisa Mestroni, Ginger Metcalf, Deborah A. Meyers, Karen H. Miga, Anna V. Mikhaylova, Julie Mikulla, Clint L. Miller, Yuan‐I Min, Mollie Minear, Ryan L. Minster, Biswapriya B. Misra, Braxton D. Mitchell, Gary F. Mitchell, Deborah Moeller, Sanghamitra Mohanty, Karen L. Mohlke, Jean Monlong, May E. Montasser, Courtney G. Montgomery, Stephen B. Montgomery, Jee‐Young Moon, Andrew E. Moran, Andrew P. Morris, Alanna C. Morrison, Arden Moscati, Thomas H. Mosley, Joanne M. Murabito, Solomon K. Musani, Shaila Musharoff, Rajeeva Musunuri, Donna M. Muzny, Stanford Mwasongwe, Josyf C. Mychaleckyj, Girish N. Nadkarni, Abhishek Nag, Rakhi P. Naik, Tetsushi Nakao, Hongmei Nan, Drew R. Nannini, Giuseppe Narzisi, Rami Nassir, Pradeep Natarajan, Anjali Nath, Matt Nayor, Benjamin M. Neale, Sergeï Nekhai, Cheryl Nelson, Sarah C. Nelson, Christopher Newton‐Cheh, Maggie Ng, Debby Ngo, Jennifer Nguyen, Lan Nguyễn, Deborah A. Nickerson, Jovia L. Nierenberg, Kari E. North, Seyed Mehdi Nouraie, Adam M. Novak, Diane J. Nugent, Paul Nyquist, Jeff O'Connell, Tim O’Connor, Brian A. O’Connor, George O'connor, Christopher J. O’Donnell, Christopher D. O’Sullivan, Heather M. Ochs‐Balcom, Elizabeth C. Oelsner, Young S. Oh, Sam S. Oh, Michael Olivier, Nicholas J. Ollberding, Nels C. Olson, Jean L. Olson, Victor E. Ortega, Kevin Osborn, Jim Ostell, Jacqueline M. Otto, Grier P. Page, David T. Paik, Nicholette Palmer, Akhil Pampana, Anita Pandit, James S. Pankow, Nathan Pankratz, George Papanicolaou, YoSon Park, Margaret M. Parker, Afshin Parsa, Jay Patel, Sanjay Patel, Aniruddh P. Patel, Benedict Paten, Candace Patterson, Gina M. Peloso, Juan Manuel, Peralta Alexandre, Pereira Marco Perez, James A. Perry, Ulrike Peters, Patricia A. Peyser, Nathan Pezant, Sam Phillips, Lawrence S. Phillips, Steve Pipe, James P. Pirruccello, Achilleas Pitsillides, Craig Pohl, Linda M. Polfus, Toni I. Pollin, Bianca Porneala, Wendy S. Post, Julia Powers Becker, Katherine Pratte, M Preethi, Boorgula Michael Preuss, Alkes Price, Jonathan K. Pritchard, Anna E. Prizment, Dmitry Prokopenko, Mike Province, Bruce M. Psaty, Shaun Purcell, Jennifer Anne Purnell, Sandra Purves, Pankaj Qasba, Qibin Qi, Huijun Qian, Yong Qian, Dandi Qiao, Zhaohui Qin, Hui‐Qi Qu, Corbin Quick, Daniel J. Rader, Nicholas Rafaels, Leslie J. Raffel, Laura M. Raffield, Dan Raftery, Sridharan Raghavan, M.F. Ragland, D. C. Rao, Laura J. Rasmussen‐Torvik, Deepa Rastogi, Aakrosh Ratan, Debashree Ray, Soumya Raychaudhuri, Susan Redline, Robert M. Reed, Elizabeth A. Regan, Amy Denise Reily, Alex P. Reiner, Kathryn M. Rexrode, Jessica A. Rhodes, Kenneth Rice, Stephen S. Rich, Michiel Rienstra, Lauren Lee Rinke, Nicolas Robine, Cassianne Robinson‐Cohen, Angela Rock, Dan M. Roden, Benjamin Steven Andrew, Thomas Rodriguez, Annabelle Rodríguez, Kathryn Roll, Jonathan Rosand, Carolina Roselli, Yohei Rosen, Samantha L. Rosenthal, Jerome I. Rotter, Ingo Ruczinski, Michael Rueschman, Alexander P. Runko, Emily M. Russell, Pamela Russell, Sarah Ruuska, Kathleen A. Ryan, Éster Cerdeira Sabino, Aniko Sabo, Nancy L. Saccone, Vandana Sachdev, Shivani Sahni, Phuwanat Sakornsakolpat, Danish Saleheen, Rany M. Salem, William Salerno, Shabnam Salimi, Juan Salomón-Andonie, Steven L. Salzberg, Jason L. Sanders, Kevin Sandow, Vijay G. Sankaran, Chloé Sarnowski, Claudia L. Satizábal, Gretchen Saunders, Richa Saxena, Gerard D. Schellenberg, Armin Schoech, Jenny Schoenberg, Charlene Schramm, Daniel R. Schrider, Karen Schwander, Chip Schwartz, David A. Schwartz, Marvin I. Schwarz, Frank C. Sciurba, Jonathan G. Seidman, Christine E. Seidman, Elizabeth Selvin, Minseok Seo, Vladimir B. Seplyarskiy, Sudha Seshadri, Amanda A. Seyerle, Aladdin H. Shadyab, Sanjiv J. Shah, Palak Shah, Amitabh Sharma, Jessica R. Shaw, Vivien Sheehan, Christopher Sheldahl, Stephanie L. Sherman, Steve Sherry, Amol C. Shetty, Wayne Hui-Heng Sheu, Kevin V. Shianna, Daichi Shimbo, M. Benjamin Shoemaker, Phyliss Sholinsky, Meghan I. Short, Lorraine Silsbee, Brian Silver, Edwin K. Silverman, Jeannette Simino, Noah Simon, Mortiz Sinner, N M Sinnott, Armstrong Colleen Sitlani, Robert Sladek, Patrick Sleiman, Craig Smail, Gustav Smith, Jennifer A. Smith, Benjamin Smith, Nicholas L. Smith, J. G. Smith, Albert V. Smith, Sylvia Smoller, Søren Snitker, Beverly Snively, M Snyder, Tamar Sofer, Mashaal Sohail, Sophie Sokolow, Karen Soldano, Wei Song, Nona Sotoodehnia, Melissa Spear, David Spies, Simon D. Spivack, C.N. Spracklen, Pothur R. Srinivas, Vinodh Srinivasasainagendra, Deepak Srivastava, David Steinberg, Debra F. Stern, Adrienne M. Stilp, Adam Stine, Nathan O. Stitziel, Elizabeth A. Streeten, Anne Sturcke, Jessica Lasky‐Su, Patrick Sullivan, Arvis Sulovari, Pavel Sumazin, Carly C. Ginter Summarell, Ryan Sun, Xiao Sun, Han Kevin Sun, Aishwarya Sundaresan, Yun Ju Sung, Shamil Sunyaev, Ida Surakka, Takeki Suzuki, Mary Sweet, Mindy D Szeto, Zachary Szpiech, Adam A. Szpiro, Carole Sztalryd, Daniel Taliun, Hua Tang, Weihong Tang, Margaret A. Taub, Kent D. Taylor, Robert E. Taylor, Matthew R.G. Taylor, Simeon I. Taylor, James G. Taylor, Bamidele O. Tayo, Marilyn J. Telen, James G. Terry, E. A. Thompson, Alastair Thomson, Timothy A. Thornton, Bharat Thyagarajan, Adrienne Tin, Lesley F. Tinker, David Tirschwell, Sarah A. Tishkoff, Hemant Tiwari, Deirdre K. Tobias, Dominic M. H. Tong, Raúl Torres, Russell P. Tracy, Martin Tristani‐Firouzi, Magan Trottier, Michael Y. Tsai, Connie W. Tsao, Dhananjay Vaidya, David Van Den Berg, Mark Van Oene, Peter VandeHaar, Lisa B. VanWagner, Jose D. Vargas, Ramachandran S. Vasan, Marie Verbanck, Karine A. Viaud, Martinez Peter Visscher, A Wright von, Holle Scott Vrieze, Michael Wagner, Jason Waligorski, Tarik Walker, Robert B. Wallace, Avram Walts, Emily S. Wan, Zhe Wang, Tao Wang, Fei Fei Wang, Biqi Wang, Penglong Wang, Yanbing Wang, Fan Wang, Heming Wang, Karol Watson, Daniel E. Weeks, Kate Wehr, Gina S. Wei, Joshua S. Weinstock, Bruce Weir Scott, W. Wen, Lu‐Chen Weng, Stéphane Wenric, Ellen M. Werner, Jennifer Wessel, Marsha M. Wheeler, Marquitta J. White, Wendy White, Peter White, Nedra Whitehead, Kerri L. Wiggins, Cristen J. Willer, Charles A.C. Williams, Kayleen Williams, Lawrence K. Williams, Scott M. 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Zody, Sebastian Zoellner, Barry Zorman, David Beame, Michael Bowers, Sharon R. Browning, Lavanya Challagundla, Matthew P. Conomos, Michelle Daya, Mariza de Andrade, Ranjan Deka, Ron Do, Leslie S. Emery, Laurent C. Francioli, Yan Gao, Steven Gazal, Stephanie M. Gogarten, María Gutiérrez‐Arcelus, Ira M. Hall, Daniel Harris, Kelley Harris, Kevin Hartman, Ryan Hernandez, Chani J. Hodonsky, Kruthika Iyer, Deepti Jain, Jicai Jiang, Andrew D. Johnson, Rich Johnston, Daniel M. Jordan, Anne E. Justice, Hyun Min Kang, Addison Keely, Tanika N. Kelly, Michael D. Kessler, Cathy C. Laurie, Xiaoming Liu, Douglas P. Loesch, Yang Luo, Daniel G. MacArthur, Ani Manichaikul, Rasika A. Mathias, Caitlin McHugh, Julie Mikulla, Ryan L. Minster, Josyf C. Mychaleckyj, Rami Nassir, Sarah C. Nelson, Deborah A. Nickerson, Jeff O'Connell, Tim O’Connor, Grier P. Page, George Papanicolaou, Alkes Price, Dmitry Prokopenko, Jennifer Anne Purnell, Soumya Raychaudhuri, Jerome I. Rotter, Armin Schoech, Daniel R. Schrider, Vladimir B. Seplyarskiy, Amol C. Shetty, Tamar Sofer, Mashaal Sohail, Wei Song, Nona Sotoodehnia, Melissa Spear, Patrick Sullivan, Shamil Sunyaev, Zachary Szpiech, Hua Tang, Kent D. Taylor, Timothy A. Thornton, Hemant Tiwari, Dominic M. H. Tong, Raúl Torres, Dhananjay Vaidya, Marie Verbanck, Kate Wehr, Bruce S. Weir, Stéphane Wenric, Quenna Wong, Lisa R. Yanek, Qiong Yang, Degui Zhi, Michael C. Zody, Sebastian Zoellner - Proceedings of the National Academy of Sciences, PNAS 2020 被引用: 112

De novo mutations (DNMs), or mutations that appear in an individual despite not being seen in their parents, are an important source of genetic variation whose impact is relevant to studies of human evolution, genetics, and disease. Utilizing high-coverage whole-genome sequencing data as part of the Trans-Omics for Precision Medicine (TOPMed) Program, we called 93,325 single-nucleotide DNMs across 1,465 trios from an array of diverse human populations, and used them to directly estimate and analyze DNM counts, rates, and spectra. We find a significant positive correlation between local recombination rate and local DNM rate, and that DNM rate explains a substantial portion (8.98 to 34.92%, depending on the model) of the genome-wide variation in population-level genetic variation from 41K unrelated TOPMed samples. Genome-wide heterozygosity does correlate with DNM rate, but only explains <1% of variation. While we are underpowered to see small differences, we do not find significant differences in DNM rate between individuals of European, African, and Latino ancestry, nor across ancestrally distinct segments within admixed individuals. However, we did find significantly fewer DNMs in Amish individuals, even when compared with other Europeans, and even after accounting for parental age and sequencing center. Specifically, we found significant reductions in the number of C→A and T→C mutations in the Amish, which seem to underpin their overall reduction in DNMs. Finally, we calculated near-zero estimates of narrow sense heritability ( h 2 ), which suggest that variation in DNM rate is significantly shaped by nonadditive genetic effects and the environment.