De novo mutations across 1,465 diverse genomes reveal mutational insights and reductions in the Amish founder population
Authors: Kessler Michael D. , Loesch Douglas P. , Perry James A. , Heard-Costa Nancy L. , Taliun Daniel , Cade Brian E. , Wang Heming , Daya Michelle , Ziniti John , Datta Soma , Celedón Juan C. , Soto-Quiros Manuel E. , Avila Lydiana , Weiss Scott T. , Barnes Kathleen , Redline Susan S. , Vasan Ramachandran S. , Johnson Andrew D. , Mathias Rasika A. , Hernandez Ryan , Wilson James G. , Nickerson Deborah A. , Abecasis Goncalo , Browning Sharon R. , Zöllner Sebastian , O’Connell Jeffrey R. , Mitchell Braxton D. ,   National Heart, Lung, and Blood Institute Trans-Omics for Precision Medicine (TOPMed) Consortium,   TOPMed Population Genetics Working Group, O’Connor Timothy D. , Aalbers Sanne , Abdalla Moustafa , Abdul-Rahman Omar , Abecasis Gonçalo , Abhyankar Avinash , Adrianto Indra , Aguet Francois , Akers Rachel , Al-Tobasei Rafet , Albert Christine , Aldred Micheala , Almasy Laura , Almeida Marcio , Alonso Alvaro , Ament Seth , Ampleford Elizabeth , An Ping , Anderson Christopher D. , Andersson Charlotte , Anugu Pramod , Appelbaum Elizabeth , Ardlie Kristin , Arking Dan , Armasu Sebastian M. , Arnett Donna K , Arruda Heather , Arvanitis Marios , Ashley-Koch Allison , Ashrani Aneel , Aslibekyan Stella , Assimes Tim , Atkinson Elizabeth , Auer Paul , Austin Thomas R. , Avery Christy , Avila-Pacheco Julian , Avillach Paul , Aviv Abraham , Avramopoulos Dimitrios , Ballantyne Christie , Balte Pallavi , Bamshad Michael , Bancks Mike , Barnard John , Barnes Kathleen , Barr R. Graham , Barron-Casella Emily , Bartz Traci , Barwick Lucas , Basu Saonli , Battle Alexis , Baumann Michael , Beame David , Beaty Terri , Beck Gerald , Becker Lewis , Becker Diane , Beer Rebecca , Begum Ferdouse , Beiser Alexa , Beitelshees Amber , Benjamin Emelia , Benos Takis , Berk-Rauch Hanna , Besich Zachary M , Bezerra Marcos , Bhatt Surya , Bi Wenjian , Bick Alexander , Bielak Larry , Biggs Mary Lou , Bis Joshua , Blackwell Thomas , Blangero John , Bleecker Eugene , Blobner Brandon , Bloom Toby , Blue Elizabeth , Bodea Corneliu , Boehnke Mike , Boerwinkle Eric , Bonas Silvia , Bowden Donald W. , Bowers Michael , Bowler Russell , Bressler Jan , Brody Jennifer , Broeckel Ulrich , Broome Jai , Brown Matthew , Brown Michael , Browning Brian , Browning Sharon , Bundy Joseph , Burchard Esteban , Burk Robert , Bustamante Carlos , Buth Erin , Butler Javed , Cade Brian , Cardwell Jonathan , Carey Vincent , Carlson Jenna , Carty Cara , Casaburi Richard , Casella James , Castaldi Peter , Chaffin Mark , Chai Jin Choul , Chakravarti Aravinda , Challagundla Lavanya , Chami Nathalie , Hang Kei , Chan Katie , Chang I-Shou , Chang Christy , Chang Yi-Cheng , Chapman Sinead , Chasman Daniel , Yii-Der Sameer Chavan , Chen Ida , Chen Wei-Min , Chen Zhanghua , Chen Han , Chen Fang , Chen Shu Hui , Chen Ming-Huei , Chen Ye , Cheng Susan , Chiu Yen-Feng , Cho Michael , Choi Seung Hoan , Chong Zechen , Chong Jessica , Christophersen Ingrid Elisabeth , Chu Audrey , Chu Shih-Kai , Chuang Lee-Ming , Chun Sung , Chung Jaeyoon , Chung Mina , Chung Ren-Hua , Cintho Mina , Civelek Ozahata Mete , Claas Steven , Clark Robert , Clarke Shoa , Claussnitzer Melina , Clemenceau Jean Rene , Clish Clary , Coady Sean , Coe Bradley , Cole John , Comhair Suzy , Conomos Matthew , Coombes Brandon , Cordes Matthew , Corlin Laura , Cornell Elaine , Correa Adolfo , Corvelo André , Courchesne Paul , Courtney Laura , Crandall Carolyn , Crapo James , Croteau-Chonka Damien , Cruz Pedro , Cupples L. Adrienne , Curran Joanne , Curtis Jeffrey , Custer Brian , Cutler Michael , Damcott Coleen , Damrauer Scott , Darbar Dawood , David Sean , Daw Warwick , Daya Michelle , de Andrade Mariza , de Vries Paul , DeBaun Michael , Defilippi Christopher , Deka Ranjan , Delaney Chris , DeLuca Tracie , DeMeo Dawn , Demissie Serkalem , Deng Xutao , Derebail Vimal , Desai Pinkal , DeStefano Anita , Devine Scott , DiCorpo Daniel , Dinardo Carla , Ding Jingzhong , Ding Jun , Divers Jasmin , Diwadkar Avantika , Do Ron , Doddapaneni Harsha , Dong Huawei , Du Margaret Mengmeng , Duan Qing , Dugan-Perez Shannon , Duggirala Ravi , Dupuis Josee , Durda Jon Peter , Dutcher Susan , Eaton Charles , Eckalbar Walter , Ehrman Clara , Eichler Evan , Ekunwe Lynette , El Boueiz Adel , Elhawary Jennifer , Ellinor Patrick , Elliott Amanda , Emdin Connor , Emery Leslie , Emond Mary , Eng Celeste , Erzurum Serpil , Esko Tonu , Evans Luke , Fan Shaohua , Fang Fang , Faraday Nauder , Farber Charles , Fardo David , Farmer Candace , Farnam Leanna , Fatkin Diane , Feitosa Mary , Felsenfeld Adam , Feng Jean , Feolo Mike , Fernandez-Rhodes Lindsay , Ferraro Nicole , Ferrer Jorge , Fetterman Jessica , Fialkowski Allison , Fingerlin Tasha , Fitzpatrick Annette , Flanagan Jonathan Michael , Flannick Jason , Fleck Katherine , Flickinger Matthew , Florez Jose , Floyd James , Fongang Bernard , Foreman Marilyn , Fornage Myriam , Foster Cassandra , Fox Caroline , Fox Ervin , Franceschini Nora , Francioli Laurent , Franklin Alan , Frazar Chris , Fretts Amanda , Fu Yi-Ping , Fu Mao , Fullerton Stephanie M. , Fulton Lucinda , Furniss Anna , Gabriel Stacey , Gagliano Sarah , Gan Taliun Weiniu , Ganesh Santhi , Ganna Andrea , Gao Yan , Garcia Melissa , Garman Lori , Garrett Michael , Garrett Melanie , Gassner Nadine , Gauderman William James , Gaulton Kyle , Gaye Amadou , Gaynor Sheila , Gaynor Brady , Gazal Steven , Gelb Bruce , Geng Xin , Geraci Mark , Germer Soren , Gerszten Robert , Gharib Sina , Gibbs Richard , Gillenwater Lucas , Gilliland Frank , Gladwin Mark , Glahn David , Godfrey Jennifer , Goff Ponce David , Gogarten Stephanie , Gondalia Rahul , Gong Da-Wei , Gonzalez Hector , Goodarzi Mark , Goodman Matthew , Gordeuk Victor , Goring Harald , Gottlieb Daniel , Goudet Jérôme , Graff Misa , Graffelman Jan , Graham Sarah , Graves Penelope , Graw Sharon , Green Nancy , Grinde Kelsey , Griswold Michael , Grove Megan , Gu C. Charles , Guan Weihua , Gui Hongsheng , Guo Xiuqing , Gupta Namrata , Gutierrez-Arcelus Maria , Haas Mary , Haessler Jeff , Hai Yang , Hajek Cassie , Hakonarson Hakon , Hale Lauren , Hall Michael , Hall Ira , Hall Amelia Weber , Hamik Anne , Handsaker Bob , Hanks Sarah , Hansen Matthew , Hanspal Manjit , Hao Luning , Hardison Ross , Haring Bernhard , Harris Kelley , Harris Daniel , Hasbani Natalie , Haussler David , Hawley Nicola , Hayden Lystra , Hayden Kathleen , He Jiang , He Karen , Heard-Costa Nancy , Heavner Ben , Heckbert Susan , Hecker Julian , Hernandez Ryan , Herndon Megan , Herrington David , Hersh Craig , Hidalgo Bertha , Highland Heather , Himes Blanca , Hirschhorn Joel , Hivert Marie-France , Hixson James , Hobbs Brian , Hodonsky Chani , Hohensee Chancellor , Hokanson John , Hong Charles , Horike-Pyne Martha , Horvath Steve , Hoth Karin , Hou Lifang , Howard-Claudio Candace M. , Hsiao Tzu-Hung , Hsiung Chao (Agnes) , Hsu Wan-Ling Nicole , Hsu Lucy , Hsu Yi-Hsiang , Hu Xiaowei , Hu Yao , Huan Tianxiao , Huang Jie , Huang Tianyi , Hubert Benjamin , Huffman Jennifer , Hughes Timothy , Hwang Tae Hyun , Hwang Shih-Jen , Hwu Chii Min , Hyacinth Hyacinth , Im Hae Kyung , Irvin Marguerite Ryan , Isasi Carmen , Itan Yuval , Iyer Kruthika Raman , Jackson Rebecca , Jain Deepti , Jaiswal Sidd , Jang Seonkyeong , Jaquish Cashell , Jarvik Gail , Jaworek Thomas , Jensen Paul , Jhun Min A , Jian Xueqiu , Jiang Jicai , Jiang Yu , Joehanes Roby , Johanson Eric , Johnsen Jill , Johnson Craig , Johnson Andrew , Johnston Rich , Jones Michelle , Jones Kimberly , Joo Jaehyun , Jordan Daniel , Jorge Kizer , Jose Aparacio , Joyce Brian , Judy Renae , Jun Goo , Justice Anne , Kachroo Priyadarshini , Kalhan Ravi , Kaltman Jonathan , Kalyani Rita , Kanchan Kanika , Kang Hyun Min , Kangeyan Divy , Kaplan Robert , Karasik David , Kardia Sharon , Kasela Silva , Kathiresan Sekar , Katz Daniel H , Kechris Katerina , Keely Addison , Keitch Richard , Kelley Spencer , Kelly Rachel S. , Kelly Tanika , Kelly Shannon , Kenny Eimear , Keramati Ali , Kessler Michael , Kestenbaum Bryan , Keys Kevin , Khan Alyna , Khera Amit , Kho Minjung , Khoury Muin , Kiel Douglas , Kim Ryan , Kim Woori , Kim Wonji , Kim Eric , King Eileen , Kinney Greg , Kinyua Frederick , Kiryluk Kamanu Krzysztof , Kittner Steven , Klarin Derek , Klauzinska Malgorzata , Kleinbrink Erica , Klemmer Robert , Knight Stacey , Knowles Emma , Ko Darae , Konkle Barbara , Kooperberg Charles , Kottgen Anna , Kourkoulis Christina , Kraja Aldi , Kral Brian , Kramer Holly , Kraus William , Krause Michael , Krauter Stephanie , Krishnan Mohanraj , Kumar Rajesh , Kuraisa Roy , Kurban Gulriz , Kwok Pui-Yan , Laederach Alain , Lakshman Preeti , Lane Kumar Jacqueline , Lane John , Lange Christoph , Lange Ethan , Lange Leslie , Lappalainen Tuuli , Lareau Caleb , Larson Martin , Larsson Katie , Lau Edward , Launer Lenore , Laurie Cathy , Laurie Cecelia , Lauzon Marie , Leal Suzanne , LeBoff Meryl , Lederer David , Lee Wen-Jane , Lee I-Te , Lee Seunggeun Shawn , Lee Seung-been Steven , Lee Eunice , Lee Christina , Lee Jiwon , Lee Grace , Lee Dongwon , LeFaive Jonathon , Lemaitre Rozenn , Lent Samantha , Lenzini Petra , Leong Aaron , Lettre Guillaume , Levin Albert , Levine David , Levy Dan , Lewis Joshua , Li Yun , Li Huiqing , Li Xiaohui , Li Zilin , Li Xingnan , Li Xihao , Li Bingshan , Liang Jingjing , Lim Elise , Limper Andrew , Lin Xihong , Lin Henry , Lin Honghuang , Lin Danyu , Lin Bridget Mengshan , Little Amarise , Liu Mengzhen , Liu Ching-Ti , Liu Yongmei , Liu Yaowu , Liu Xiaoming , Liu Delong , Liu Dajiang , Liu Chunyu , Liu Qing , Liu Jingmin , Liu Simin , Locke Adam , Loesch Douglas , London Stephanie , Long Michelle , Longchamps Ryan , Longstreth Will , Loos Ruth , Lubitz Steven , Lunetta Kathryn , Luo Yang , Luo James , Lutz Sharon , Ma Yanlin , MacArthur Daniel , Madahar Purnema , Mahajan Anubha , Mahaney Michael , Maher Joe , Mainous Arch (Chip) , Majarian Timothy , Mak Angel CY , Malhotra Rajeev , Manichaikul Ani , Manning Alisa , Manson JoAnn , Marini Sandro , Martin Lisa , Martinez Fernando , Mathai Susan , Mathias Rasika , May Susanne , Mayeux Richard , McArdle Patrick , McCarroll Steve , McCarthy Mark , McDonald Merry-Lynn , McDonough Barbara , McFarland Sean , McGarvey Stephen , McGoldrick Daniel , McGuire Daniel , McHugh Caitlin , McKnight Barbara , McLenithan John , McManus David , McSherry Tonya , Meeks Shannon , Mei Hao , Meigs James , Mendelson Michael , Mensah George , Mercader Josep , Merriman Tony , Messerlian Geralyn , Mestroni Luisa , Metcalf Ginger , Meyers Deborah A , Miga Karen , Mikhaylova Anna , Mikulla Julie , Miller Clint , Min Nancy , Minear Mollie , Minster Ryan L , Misra Biswapriya , Mitchell Braxton D. , Mitchell Gary F. , Moeller Deborah , Mohanty Sanghamitra , Mohlke Karen , Monlong Jean , Montasser May E. , Montgomery Courtney , Montgomery Stephen , Moon Jee-Young , Moran Andrew , Morris Andrew , Morrison Alanna C , Moscati Arden , Mosley Thomas , Murabito Joanne , Musani Solomon , Musharoff Shaila , Musunuri Rajeeva Lochan , Muzny Donna , Mwasongwe Stanford , Mychaleckyj Josyf C , Nadkarni Girish , Nag Abhishek , Naik Rakhi , Nakao Tetsushi , Nan Hongmei , Nannini Drew , Narzisi Giuseppe , Nassir Rami , Natarajan Pradeep , Nath Anjali , Nayor Matt , Neale Benjamin , Nekhai Sergei , Nelson Cheryl , Nelson Sarah C. , Newton-Cheh Christopher , Ng Maggie , Ngo Debby , Nguyen Jennifer , Nguyen Lan , Nickerson Deborah , Nierenberg Jovia , North Kari , Nouraie Seyed Mehdi , Novak Adam , Nugent Diane , Nyquist Paul , O'Connell Jeff , O'Connor Tim , O'Connor Brian , O'Connor George , O'Donnell Christopher , O'Sullivan Christopher , Ochs-Balcom Heather , Oelsner Elizabeth , Oh Young S. , Oh Sam , Olivier Michael , Ollberding Nicholas , Olson Nels , Olson Jean L. , Ortega Victor , Osborn Kevin , Ostell Jim , Otto Jacqueline , Page Grier , Paik David , Palmer Nicholette , Pampana Akhil , Pandit Anita , Pankow James , Pankratz Nathan , Papanicolaou George , Park Yoson , Parker Margaret , Parsa Afshin , Patel Jay , Patel Sanjay , Patel Aniruddh , Paten Benedict , Patterson Candace , Peloso Gina , Manuel Juan , Alexandre Peralta , Perez Pereira Marco , Perry James , Peters Ulrike , Peyser Patricia , Pezant Nathan , Phillips Sam , Phillips Lawrence S , Pipe Steve , Pirruccello James , Pitsillides Achilleas , Pohl Craig , Polfus Linda , Pollin Toni , Porneala Bianca , Post Wendy , Becker Julia Powers , Pratte Katherine , Preethi Meher , Preuss Boorgula Michael , Price Alkes , Pritchard Jonathan , Prizment Anna , Prokopenko Dmitry , Province Mike , Psaty Bruce , Purcell Shaun , Purnell Jennifer Anne , Purves Sandra , Qasba Pankaj , Qi Qibin , Qian Huijun , Qian Yong , Qiao Dandi , Qin Zhaohui , Qu Huiqi , Quick Corbin , Rader Daniel , Rafaels Nicholas , Raffel Leslie , Raffield Laura , Raftery Dan , Raghavan Sridharan , Ragland Margaret F. , Rao D.C. , Rasmussen-Torvik Laura , Rastogi Deepa , Ratan Aakrosh , Ray Debashree , Raychaudhuri Soumya , Redline Susan , Reed Robert , Regan Elizabeth , Reily Amy D. , Reiner Alex , Rexrode Kathryn , Rhodes Jessica , Rice Ken , Rich Stephen , Rienstra Michiel , Rinke Lauren Lee , Robine Nicolas , Robinson-Cohen Cassianne , Rock Angela , Roden Dan , Andrew Benjamin , Rodriguez Thomas , Rodriguez Annabelle , Roll Kathryn (Kaye) , Rosand Jonathan , Roselli Carolina , Rosen Yohei , Rosenthal Samantha , Rotter Jerome , Ruczinski Ingo , Rueschman Michael , Runko Alexander , Russell Emily , Russell Pamela , Ruuska Sarah , Ryan Kathleen , Sabino Ester Cerdeira , Sabo Aniko , Saccone Nancy , Sachdev Vandana , Sahni Shivani , Sakornsakolpat Phuwanat , Saleheen Danish , Salem Rany , Salerno William , Salimi Shabnam , Salomon-Andonie Juan , Salzberg Steven , Sanders Jason L. , Sandow Kevin , Sankaran Vijay , Sarnowski Chloé , Satizabal Claudia , Saunders Gretchen , Saxena Richa , Schellenberg Gerard , Schoech Armin , Schoenberg Jenny , Schramm Charlene , Schrider Daniel , Schwander Karen , Schwartz Chip , Schwartz David , Schwarz Marvin , Sciurba Frank , Seidman Jonathan , Seidman Christine , Selvin Elizabeth , Seo Minseok , Seplyarskiy Vladimir , Seshadri Sudha , Seyerle Amanda , Shadyab Aladdin , Shah Sanjiv , Shah Palak , Sharma Amitabh , Shaw Jessica R , Sheehan Vivien , Sheldahl Christopher John , Sherman Stephanie , Sherry Steve , Shetty Amol , Sheu Wayne Hui-Heng , Shianna Kevin , Shimbo Daichi , Shoemaker M. Benjamin , Sholinsky Phyliss , Short Meghan I , Silsbee Lorraine , Silver Brian , Silverman Edwin , Simino Jeannette , Simon Noah , Sinner Mortiz , Sinnott Nasa , Sitlani Armstrong Colleen , Sladek Robert , Sleiman Patrick , Smail Craig , Smith Gustav , Smith Jennifer , Smith Benjamin , Smith Nicholas , Smith Josh , Smith Albert Vernon , Smoller Sylvia , Snitker Soren , Snively Beverly , Snyder Michael , Sofer Tamar , Sohail Mashaal , Sokolow Sophie , Soldano Karen , Song Wei , Sotoodehnia Nona , Spear Melissa , Spies David , Spivack Simon , Spracklen Cassie , Srinivas Pothur , Srinivasasainagendra Vinodh , Srivastava Deepak , Steinberg David , Stern Debra , Stilp Adrienne , Stine Adam , Stitziel Nathan , Streeten Elizabeth , Sturcke Anne , Su Jessica Lasky , Sullivan Patrick , Sulovari Arvis , Sumazin Pavel , Summarell Carly , Sun Ryan , Sun Xiao , Sun Han Kevin , Sundaresan Aishwarya , Sung Yun Ju , Sunyaev Shamil R , Surakka Ida , Suzuki Takeki , Sweet Mary , Szeto Mindy , Szpiech Zachary , Szpiro Adam , Sztalryd Carole , Taliun Daniel , Tang Hua , Tang Weihong , Taub Margaret , Taylor Kent D. , Taylor Robert E , Taylor Matthew , Taylor Simeon , Taylor James G. , VI Bamidele Tayo , Telen Marilyn , Terry James Gregory , Thompson Elizabeth , Thomson Alastair , Thornton Timothy A. , Thyagarajan Bharat , Tin Adrienne , Tinker Lesley , Tirschwell David , Tishkoff Sarah , Tiwari Hemant , Tobias Deirdre , Tong Dominic , Torres Raul , Tracy Russell , Tristani Martin , Trottier Magan , Tsai Michael , Tsao Connie , Vaidya Dhananjay , Van Den Berg David , Van Oene Mark , VandeHaar Peter , VanWagner Lisa , Vargas Jose , Vasan Ramachandran S. , Verbanck Marie , Viaud Karine A. , Visscher Martinez Peter , Von Ann , Vrieze Holle Scott , Wagner Michael , Waligorski Jason , Walker Tarik , Wallace Robert , Walts Avram , Wan Emily , Wang Zhe , Wang Tao , Wang Fei Fei , Wang Biqi Becky , Wang Penglong , Wang Yanbing , Wang Fan , Wang Heming , Watson Karol , Weeks Daniel E. , Wehr Kate , Wei Gina , Weinstock Joshua , Scott Bruce Weir , Wen Weiss Fayuan , Weng Lu-Chen , Wenric Stephane , Werner Ellen , Wessel Jennifer , Wheeler Marsha , White Marquitta , White Wendy , White Peter , Whitehead Nedra , Wiggins Kerri , Willer Cristen , Williams Charles , Williams Kayleen , Williams L. Keoki , Williams Scott , Williams-Nguyen Jessica , Wilson James , Wilson Carla , Wing Mary Kate , Winters Karen , Wojczynski Mary , Wolford Brooke , Wong Quenna , Wu Peitao , Wu Joseph , Wu Ann , Xia Lluvia , Xiao Chunlin , Xiao Shujie , Xu Hanfei , Xu Weiling , Xu Shujing , Xu Huichun , Yanek Lisa , Yang Yu-Chung , Yang Chaojie , Yang Qiong , Yang Ivana , Yano Yuichiro , Yao Jie , Yaschenko Eugene , Yau Michelle , Yin Xianyong , Yoneyama Sachiko , Young Bessie , Young Hannah , Young Kristin , Young Tracey , Young Kendra , Youngblood Marston , Yu Bing , Yu Chaoyu , Zaghloul Norann , Zalokar-Newton Mira , Zare Habil , Zein Joe , Zekavat Maryam , Man Zhang Grace , Zhang Wei , Zhang Xiaoyu , Zhang Ying , Zhang Jerry , Zhang Xinruo , Zhang Jingwen , Zhang Xu , Zhang Yingze , Zhao Snow Xueyan , Zhao Lue Ping , Zhao Xutong , Zhao Wei , Zheng Yinan , Zheng Xiuwen , Zhi Degui , Zhou Hufeng , Zhou Lisheng , Zhou Xiang , Zhou Yunyun , Zhu Luke , Zhu Xiaofeng , Zody Michael , Zoellner Sebastian , Zorman Barry , Beame David , Bowers Michael , Browning Sharon , Challagundla Lavanya , Conomos Matthew , Daya Michelle , de Andrade Mariza , Deka Ranjan , Do Ron , Emery Leslie , Francioli Laurent , Gao Yan , Gazal Steven , Gogarten Stephanie , Gutierrez-Arcelus Maria , Hall Ira , Harris Daniel , Harris Kelley , Hartman Kevin , Hernandez Ryan , Hodonsky Chani , Iyer Kruthika Raman , Jain Deepti , Jiang Jicai , Johnson Andrew , Johnston Rich , Jordan Daniel , Justice Anne , Kang Hyun Min , Keely Addison , Kelly Tanika , Kessler Michael , Laurie Cathy , Liu Xiaoming , Loesch Douglas , Luo Yang , MacArthur Daniel , Manichaikul Ani , Mathias Rasika , McHugh Caitlin , Mikulla Julie , Minster Ryan L , Mychaleckyj Josyf C , Nassir Rami , Nelson Sarah C. , Nickerson Deborah , O'Connell Jeff , O'Connor Tim , Page Grier , Papanicolaou George , Price Alkes , Prokopenko Dmitry , Purnell Jennifer Anne , Raychaudhuri Soumya , Rotter Jerome , Schoech Armin , Schrider Daniel , Seplyarskiy Vladimir , Shetty Amol , Sofer Tamar , Sohail Mashaal , Song Wei , Sotoodehnia Nona , Spear Melissa , Sullivan Patrick , Sunyaev Shamil R , Szpiech Zachary , Tang Hua , Taylor Kent D. , Thornton Timothy A. , Tiwari Hemant , Tong Dominic , Torres Raul , Vaidya Dhananjay , Verbanck Marie , Wehr Kate , Weir Bruce , Wenric Stephane , Wong Quenna , Yanek Lisa , Yang Qiong , Zhi Degui , Zody Michael , Zoellner Sebastian 
Published: January 2020

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 (h2), which suggest that variation in DNM rate is significantly shaped by nonadditive genetic effects and the environment.