Letters

  • Letter |

    Quantitative ChIP–seq analysis maps G-quadruplex (G4) DNA structures in breast cancer patient-derived tumor xenograft (PDTX) models. G4-based subtypes highlight additional tumor heterogeneity in the integrative cluster (IC) system.

    • Robert Hänsel-Hertsch
    • , Angela Simeone
    • , Abigail Shea
    • , Winnie W. I. Hui
    • , Katherine G. Zyner
    • , Giovanni Marsico
    • , Oscar M. Rueda
    • , Alejandra Bruna
    • , Alistair Martin
    • , Xiaoyun Zhang
    • , Santosh Adhikari
    • , David Tannahill
    • , Carlos Caldas
    •  & Shankar Balasubramanian
  • Letter |

    Nucleic acid processing by the cytoplasmic exonuclease TREX1 and cytosine editing by APOBEC3B drive chromothripsis and kataegis during telomere crisis.

    • John Maciejowski
    • , Aikaterini Chatzipli
    • , Alexandra Dananberg
    • , Kevan Chu
    • , Eleonore Toufektchan
    • , Leszek J. Klimczak
    • , Dmitry A. Gordenin
    • , Peter J. Campbell
    •  & Titia de Lange
  • Letter |

    Genome-wide analysis in 212,453 Japanese individuals identifies loci associated with 42 diseases. Comparative analysis with European populations identifies East Asian–specific associations.

    • Kazuyoshi Ishigaki
    • , Masato Akiyama
    • , Masahiro Kanai
    • , Atsushi Takahashi
    • , Eiryo Kawakami
    • , Hiroki Sugishita
    • , Saori Sakaue
    • , Nana Matoba
    • , Siew-Kee Low
    • , Yukinori Okada
    • , Chikashi Terao
    • , Tiffany Amariuta
    • , Steven Gazal
    • , Yuta Kochi
    • , Momoko Horikoshi
    • , Ken Suzuki
    • , Kaoru Ito
    • , Satoshi Koyama
    • , Kouichi Ozaki
    • , Shumpei Niida
    • , Yasushi Sakata
    • , Yasuhiko Sakata
    • , Takashi Kohno
    • , Kouya Shiraishi
    • , Yukihide Momozawa
    • , Makoto Hirata
    • , Koichi Matsuda
    • , Masashi Ikeda
    • , Nakao Iwata
    • , Shiro Ikegawa
    • , Ikuyo Kou
    • , Toshihiro Tanaka
    • , Hidewaki Nakagawa
    • , Akari Suzuki
    • , Tomomitsu Hirota
    • , Mayumi Tamari
    • , Kazuaki Chayama
    • , Daiki Miki
    • , Masaki Mori
    • , Satoshi Nagayama
    • , Yataro Daigo
    • , Yoshio Miki
    • , Toyomasa Katagiri
    • , Osamu Ogawa
    • , Wataru Obara
    • , Hidemi Ito
    • , Teruhiko Yoshida
    • , Issei Imoto
    • , Takashi Takahashi
    • , Chizu Tanikawa
    • , Takao Suzuki
    • , Nobuaki Sinozaki
    • , Shiro Minami
    • , Hiroki Yamaguchi
    • , Satoshi Asai
    • , Yasuo Takahashi
    • , Ken Yamaji
    • , Kazuhisa Takahashi
    • , Tomoaki Fujioka
    • , Ryo Takata
    • , Hideki Yanai
    • , Akihide Masumoto
    • , Yukihiro Koretsune
    • , Hiromu Kutsumi
    • , Masahiko Higashiyama
    • , Shigeo Murayama
    • , Naoko Minegishi
    • , Kichiya Suzuki
    • , Kozo Tanno
    • , Atsushi Shimizu
    • , Taiki Yamaji
    • , Motoki Iwasaki
    • , Norie Sawada
    • , Hirokazu Uemura
    • , Keitaro Tanaka
    • , Mariko Naito
    • , Makoto Sasaki
    • , Kenji Wakai
    • , Shoichiro Tsugane
    • , Masayuki Yamamoto
    • , Kazuhiko Yamamoto
    • , Yoshinori Murakami
    • , Yusuke Nakamura
    • , Soumya Raychaudhuri
    • , Johji Inazawa
    • , Toshimasa Yamauchi
    • , Takashi Kadowaki
    • , Michiaki Kubo
    •  & Yoichiro Kamatani
  • Letter |

    CTCF is dispensable for transdifferentiation of B cells into induced macrophages despite widespread loss of topologically associating domains. CTCF depletion impairs upregulation of inflammatory genes after endotoxin exposure by destabilizing promoter–enhancer interactions.

    • Grégoire Stik
    • , Enrique Vidal
    • , Mercedes Barrero
    • , Sergi Cuartero
    • , Maria Vila-Casadesús
    • , Julen Mendieta-Esteban
    • , Tian V. Tian
    • , Jinmi Choi
    • , Clara Berenguer
    • , Amaya Abad
    • , Beatrice Borsari
    • , François le Dily
    • , Patrick Cramer
    • , Marc A. Marti-Renom
    • , Ralph Stadhouders
    •  & Thomas Graf
  • Letter |

    Genome-wide analysis identifies 32 loci associated with breast cancer susceptibility, accounting for estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 status and tumor grade.

    • Haoyu Zhang
    • , Thomas U. Ahearn
    • , Julie Lecarpentier
    • , Daniel Barnes
    • , Jonathan Beesley
    • , Guanghao Qi
    • , Xia Jiang
    • , Tracy A. O’Mara
    • , Ni Zhao
    • , Manjeet K. Bolla
    • , Alison M. Dunning
    • , Joe Dennis
    • , Qin Wang
    • , Zumuruda Abu Ful
    • , Kristiina Aittomäki
    • , Irene L. Andrulis
    • , Hoda Anton-Culver
    • , Volker Arndt
    • , Kristan J. Aronson
    • , Banu K. Arun
    • , Paul L. Auer
    • , Jacopo Azzollini
    • , Daniel Barrowdale
    • , Heiko Becher
    • , Matthias W. Beckmann
    • , Sabine Behrens
    • , Javier Benitez
    • , Marina Bermisheva
    • , Katarzyna Bialkowska
    • , Ana Blanco
    • , Carl Blomqvist
    • , Natalia V. Bogdanova
    • , Stig E. Bojesen
    • , Bernardo Bonanni
    • , Davide Bondavalli
    • , Ake Borg
    • , Hiltrud Brauch
    • , Hermann Brenner
    • , Ignacio Briceno
    • , Annegien Broeks
    • , Sara Y. Brucker
    • , Thomas Brüning
    • , Barbara Burwinkel
    • , Saundra S. Buys
    • , Helen Byers
    • , Trinidad Caldés
    • , Maria A. Caligo
    • , Mariarosaria Calvello
    • , Daniele Campa
    • , Jose E. Castelao
    • , Jenny Chang-Claude
    • , Stephen J. Chanock
    • , Melissa Christiaens
    • , Hans Christiansen
    • , Wendy K. Chung
    • , Kathleen B. M. Claes
    • , Christine L. Clarke
    • , Sten Cornelissen
    • , Fergus J. Couch
    • , Angela Cox
    • , Simon S. Cross
    • , Kamila Czene
    • , Mary B. Daly
    • , Peter Devilee
    • , Orland Diez
    • , Susan M. Domchek
    • , Thilo Dörk
    • , Miriam Dwek
    • , Diana M. Eccles
    • , Arif B. Ekici
    • , D. Gareth Evans
    • , Peter A. Fasching
    • , Jonine Figueroa
    • , Lenka Foretova
    • , Florentia Fostira
    • , Eitan Friedman
    • , Debra Frost
    • , Manuela Gago-Dominguez
    • , Susan M. Gapstur
    • , Judy Garber
    • , José A. García-Sáenz
    • , Mia M. Gaudet
    • , Simon A. Gayther
    • , Graham G. Giles
    • , Andrew K. Godwin
    • , Mark S. Goldberg
    • , David E. Goldgar
    • , Anna González-Neira
    • , Mark H. Greene
    • , Jacek Gronwald
    • , Pascal Guénel
    • , Lothar Häberle
    • , Eric Hahnen
    • , Christopher A. Haiman
    • , Christopher R. Hake
    • , Per Hall
    • , Ute Hamann
    • , Elaine F. Harkness
    • , Bernadette A. M. Heemskerk-Gerritsen
    • , Peter Hillemanns
    • , Frans B. L. Hogervorst
    • , Bernd Holleczek
    • , Antoinette Hollestelle
    • , Maartje J. Hooning
    • , Robert N. Hoover
    • , John L. Hopper
    • , Anthony Howell
    • , Hanna Huebner
    • , Peter J. Hulick
    • , Evgeny N. Imyanitov
    • , Claudine Isaacs
    • , Louise Izatt
    • , Agnes Jager
    • , Milena Jakimovska
    • , Anna Jakubowska
    • , Paul James
    • , Ramunas Janavicius
    • , Wolfgang Janni
    • , Esther M. John
    • , Michael E. Jones
    • , Audrey Jung
    • , Rudolf Kaaks
    • , Pooja Middha Kapoor
    • , Beth Y. Karlan
    • , Renske Keeman
    • , Sofia Khan
    • , Elza Khusnutdinova
    • , Cari M. Kitahara
    • , Yon-Dschun Ko
    • , Irene Konstantopoulou
    • , Linetta B. Koppert
    • , Stella Koutros
    • , Vessela N. Kristensen
    • , Anne-Vibeke Laenkholm
    • , Diether Lambrechts
    • , Susanna C. Larsson
    • , Pierre Laurent-Puig
    • , Conxi Lazaro
    • , Emilija Lazarova
    • , Flavio Lejbkowicz
    • , Goska Leslie
    • , Fabienne Lesueur
    • , Annika Lindblom
    • , Jolanta Lissowska
    • , Wing-Yee Lo
    • , Jennifer T. Loud
    • , Jan Lubinski
    • , Alicja Lukomska
    • , Robert J. MacInnis
    • , Arto Mannermaa
    • , Mehdi Manoochehri
    • , Siranoush Manoukian
    • , Sara Margolin
    • , Maria Elena Martinez
    • , Laura Matricardi
    • , Lesley McGuffog
    • , Catriona McLean
    • , Noura Mebirouk
    • , Alfons Meindl
    • , Usha Menon
    • , Austin Miller
    • , Elvira Mingazheva
    • , Marco Montagna
    • , Anna Marie Mulligan
    • , Claire Mulot
    • , Taru A. Muranen
    • , Katherine L. Nathanson
    • , Susan L. Neuhausen
    • , Heli Nevanlinna
    • , Patrick Neven
    • , William G. Newman
    • , Finn C. Nielsen
    • , Liene Nikitina-Zake
    • , Jesse Nodora
    • , Kenneth Offit
    • , Edith Olah
    • , Olufunmilayo I. Olopade
    • , Håkan Olsson
    • , Nick Orr
    • , Laura Papi
    • , Janos Papp
    • , Tjoung-Won Park-Simon
    • , Michael T. Parsons
    • , Bernard Peissel
    • , Ana Peixoto
    • , Beth Peshkin
    • , Paolo Peterlongo
    • , Julian Peto
    • , Kelly-Anne Phillips
    • , Marion Piedmonte
    • , Dijana Plaseska-Karanfilska
    • , Karolina Prajzendanc
    • , Ross Prentice
    • , Darya Prokofyeva
    • , Brigitte Rack
    • , Paolo Radice
    • , Susan J. Ramus
    • , Johanna Rantala
    • , Muhammad U. Rashid
    • , Gad Rennert
    • , Hedy S. Rennert
    • , Harvey A. Risch
    • , Atocha Romero
    • , Matti A. Rookus
    • , Matthias Rübner
    • , Thomas Rüdiger
    • , Emmanouil Saloustros
    • , Sarah Sampson
    • , Dale P. Sandler
    • , Elinor J. Sawyer
    • , Maren T. Scheuner
    • , Rita K. Schmutzler
    • , Andreas Schneeweiss
    • , Minouk J. Schoemaker
    • , Ben Schöttker
    • , Peter Schürmann
    • , Leigha Senter
    • , Priyanka Sharma
    • , Mark E. Sherman
    • , Xiao-Ou Shu
    • , Christian F. Singer
    • , Snezhana Smichkoska
    • , Penny Soucy
    • , Melissa C. Southey
    • , John J. Spinelli
    • , Jennifer Stone
    • , Dominique Stoppa-Lyonnet
    • , Anthony J. Swerdlow
    • , Csilla I. Szabo
    • , Rulla M. Tamimi
    • , William J. Tapper
    • , Jack A. Taylor
    • , Manuel R. Teixeira
    • , MaryBeth Terry
    • , Mads Thomassen
    • , Darcy L. Thull
    • , Marc Tischkowitz
    • , Amanda E. Toland
    • , Rob A. E. M. Tollenaar
    • , Ian Tomlinson
    • , Diana Torres
    • , Melissa A. Troester
    • , Thérèse Truong
    • , Nadine Tung
    • , Michael Untch
    • , Celine M. Vachon
    • , Ans M. W. van den Ouweland
    • , Lizet E. van der Kolk
    • , Elke M. van Veen
    • , Elizabeth J. vanRensburg
    • , Ana Vega
    • , Barbara Wappenschmidt
    • , Clarice R. Weinberg
    • , Jeffrey N. Weitzel
    • , Hans Wildiers
    • , Robert Winqvist
    • , Alicja Wolk
    • , Xiaohong R. Yang
    • , Drakoulis Yannoukakos
    • , Wei Zheng
    • , Kristin K. Zorn
    • , Roger L. Milne
    • , Peter Kraft
    • , Jacques Simard
    • , Paul D. P. Pharoah
    • , Kyriaki Michailidou
    • , Antonis C. Antoniou
    • , Marjanka K. Schmidt
    • , Georgia Chenevix-Trench
    • , Douglas F. Easton
    • , Nilanjan Chatterjee
    •  & Montserrat García-Closas
  • Letter |

    Cas9 expression induces DNA damage and activates the p53 pathway, and it can lead to the selection of cells with p53-inactivating mutations. Cas9 is less active in wild-type TP53 cell lines than in TP53-mutant cell lines.

    • Oana M. Enache
    • , Veronica Rendo
    • , Mai Abdusamad
    • , Daniel Lam
    • , Desiree Davison
    • , Sangita Pal
    • , Naomi Currimjee
    • , Julian Hess
    • , Sasha Pantel
    • , Anwesha Nag
    • , Aaron R. Thorner
    • , John G. Doench
    • , Francisca Vazquez
    • , Rameen Beroukhim
    • , Todd R. Golub
    •  & Uri Ben-David
  • Letter |

    Genome-wide association analysis for morphological traits across 350 elite maize inbred lines in Chinese and US germplasm identifies loci and genomic regions representing the targets of selection during modern maize breeding.

    • Baobao Wang
    • , Zechuan Lin
    • , Xin Li
    • , Yongping Zhao
    • , Binbin Zhao
    • , Guangxia Wu
    • , Xiaojing Ma
    • , Hai Wang
    • , Yurong Xie
    • , Quanquan Li
    • , Guangshu Song
    • , Dexin Kong
    • , Zhigang Zheng
    • , Hongbin Wei
    • , Rongxin Shen
    • , Hong Wu
    • , Cuixia Chen
    • , Zhaodong Meng
    • , Tianyu Wang
    • , Yu Li
    • , Xinhai Li
    • , Yanhui Chen
    • , Jinsheng Lai
    • , Matthew B. Hufford
    • , Jeffrey Ross-Ibarra
    • , Hang He
    •  & Haiyang Wang
  • Letter |

    Single-cell analysis of mouse hematopoietic stem cells shows that mutations in DNA methylation genes change the frequencies of erythroid versus myelomonocytic progenitors, owing to differential CpG enrichment in transcription factor binding motifs.

    • Franco Izzo
    • , Stanley C. Lee
    • , Asaf Poran
    • , Ronan Chaligne
    • , Federico Gaiti
    • , Baptiste Gross
    • , Rekha R. Murali
    • , Sunil D. Deochand
    • , Chelston Ang
    • , Philippa Wyndham Jones
    • , Anna S. Nam
    • , Kyu-Tae Kim
    • , Steven Kothen-Hill
    • , Rafael C. Schulman
    • , Michelle Ki
    • , Priscillia Lhoumaud
    • , Jane A. Skok
    • , Aaron D. Viny
    • , Ross L. Levine
    • , Ephraim Kenigsberg
    • , Omar Abdel-Wahab
    •  & Dan A. Landau
  • Letter |

    Whole-exome sequencing of human brain metastases from lung adenocarcinoma uncovers new drivers by comparison of somatic alteration frequencies in brain metastasis cases to those in primary lung adenocarcinomas.

    • David J. H. Shih
    • , Naema Nayyar
    • , Ivanna Bihun
    • , Ibiayi Dagogo-Jack
    • , Corey M. Gill
    • , Elisa Aquilanti
    • , Mia Bertalan
    • , Alexander Kaplan
    • , Megan R. D’Andrea
    • , Ugonma Chukwueke
    • , Franziska Maria Ippen
    • , Christopher Alvarez-Breckenridge
    • , Nicholas D. Camarda
    • , Matthew Lastrapes
    • , Devin McCabe
    • , Ben Kuter
    • , Benjamin Kaufman
    • , Matthew R. Strickland
    • , Juan Carlos Martinez-Gutierrez
    • , Deepika Nagabhushan
    • , Magali De Sauvage
    • , Michael D. White
    • , Brandyn A. Castro
    • , Kaitlin Hoang
    • , Andrew Kaneb
    • , Emily D. Batchelor
    • , Sun Ha Paek
    • , Sun Hye Park
    • , Maria Martinez-Lage
    • , Anna S. Berghoff
    • , Parker Merrill
    • , Elizabeth R. Gerstner
    • , Tracy T. Batchelor
    • , Matthew P. Frosch
    • , Ryan P. Frazier
    • , Darrell R. Borger
    • , A. John Iafrate
    • , Bruce E. Johnson
    • , Sandro Santagata
    • , Matthias Preusser
    • , Daniel P. Cahill
    • , Scott L. Carter
    •  & Priscilla K. Brastianos
  • Letter |

    Deep mRNA sequencing at eight time points during memory CD4+ T cell activation identifies widespread dynamic allele-specific expression events that are enriched in HLA and other autoimmune disease loci.

    • Maria Gutierrez-Arcelus
    • , Yuriy Baglaenko
    • , Jatin Arora
    • , Susan Hannes
    • , Yang Luo
    • , Tiffany Amariuta
    • , Nikola Teslovich
    • , Deepak A. Rao
    • , Joerg Ermann
    • , A. Helena Jonsson
    • , Cristina Navarrete
    • , Stephen S. Rich
    • , Kent D. Taylor
    • , Jerome I. Rotter
    • , Peter K. Gregersen
    • , Tonu Esko
    • , Michael B. Brenner
    •  & Soumya Raychaudhuri
  • Letter |

    Experiments in developing human erythroid cells show that LIN28B controls hemoglobin switching by directly suppressing BCL11A translation, independently of its role in regulating let-7 microRNA biogenesis.

    • Anindita Basak
    • , Mathias Munschauer
    • , Caleb A. Lareau
    • , Kara E. Montbleau
    • , Jacob C. Ulirsch
    • , Christina R. Hartigan
    • , Monica Schenone
    • , John Lian
    • , Yaomei Wang
    • , Yumin Huang
    • , Xianfang Wu
    • , Lee Gehrke
    • , Charles M. Rice
    • , Xiuli An
    • , Helen A. Christou
    • , Narla Mohandas
    • , Steven A. Carr
    • , Jane-Jane Chen
    • , Stuart H. Orkin
    • , Eric S. Lander
    •  & Vijay G. Sankaran
  • Letter |

    Combined genomic and transcriptomic approaches identify the landscape of extrachromosomal circular DNA in neuroblastoma and reveal that extrachromosomal circular DNA is a major source of somatic rearrangements.

    • Richard P. Koche
    • , Elias Rodriguez-Fos
    • , Konstantin Helmsauer
    • , Martin Burkert
    • , Ian C. MacArthur
    • , Jesper Maag
    • , Rocio Chamorro
    • , Natalia Munoz-Perez
    • , Montserrat Puiggròs
    • , Heathcliff Dorado Garcia
    • , Yi Bei
    • , Claudia Röefzaad
    • , Victor Bardinet
    • , Annabell Szymansky
    • , Annika Winkler
    • , Theresa Thole
    • , Natalie Timme
    • , Katharina Kasack
    • , Steffen Fuchs
    • , Filippos Klironomos
    • , Nina Thiessen
    • , Eric Blanc
    • , Karin Schmelz
    • , Annette Künkele
    • , Patrick Hundsdörfer
    • , Carolina Rosswog
    • , Jessica Theissen
    • , Dieter Beule
    • , Hedwig Deubzer
    • , Sascha Sauer
    • , Joern Toedling
    • , Matthias Fischer
    • , Falk Hertwig
    • , Roland F. Schwarz
    • , Angelika Eggert
    • , David Torrents
    • , Johannes H. Schulte
    •  & Anton G. Henssen
  • Letter |

    Mutations in ADAMTS19 lead to progressive heart valve disease in humans. Analysis of mice lacking Adamts19 highlights the role of a Wnt–Adamts19–Klf2 axis in proper valve function.

    • Florian Wünnemann
    • , Asaf Ta-Shma
    • , Christoph Preuss
    • , Severine Leclerc
    • , Patrick Piet van Vliet
    • , Andrea Oneglia
    • , Maryse Thibeault
    • , Emily Nordquist
    • , Joy Lincoln
    • , Franka Scharfenberg
    • , Christoph Becker-Pauly
    • , Philipp Hofmann
    • , Kirstin Hoff
    • , Enrique Audain
    • , Hans-Heiner Kramer
    • , Wojciech Makalowski
    • , Amiram Nir
    • , Sebastian S. Gerety
    • , Matthew Hurles
    • , Johanna Comes
    • , Anne Fournier
    • , Hanna Osinska
    • , Jeffrey Robins
    • , Michel Pucéat
    • , Harry C. Dietz
    • , Andrew S. McCallion
    • , Gregor Andelfinger
    • , Bart L. Loeys
    • , Lut Van Laer
    • , Per Eriksson
    • , Salah A. Mohamed
    • , Luc Mertens
    • , Anders Franco-Cereceda
    • , Seema Mital
    • , Orly Elpeleg
    • , Marc-Phillip Hitz
    •  & Gregor Andelfinger
  • Letter |

    N6-methyladenosine (m6A) is prevalent at RNA:DNA hybrids in human pluripotent stem cells. The m6A reader YTHDF2 interacts with R-loop-enriched loci in dividing cells, and YTHDF2 loss leads to increased R-loop levels and accumulation of γH2AX.

    • Abdulkadir Abakir
    • , Tom C. Giles
    • , Agnese Cristini
    • , Jeremy M. Foster
    • , Nan Dai
    • , Marta Starczak
    • , Alejandro Rubio-Roldan
    • , Miaomiao Li
    • , Maria Eleftheriou
    • , James Crutchley
    • , Luke Flatt
    • , Lorraine Young
    • , Daniel J. Gaffney
    • , Chris Denning
    • , Bjørn Dalhus
    • , Richard D. Emes
    • , Daniel Gackowski
    • , Ivan R. Corrêa Jr
    • , Jose L. Garcia-Perez
    • , Arne Klungland
    • , Natalia Gromak
    •  & Alexey Ruzov
  • Letter |

    Combining CRISPRi-FlowFISH to perturb enhancers with an activity-by-contact model to predict complex connections allows systematic mapping of enhancer–gene connections in a given cell type, on the basis of chromatin-state measurements.

    • Charles P. Fulco
    • , Joseph Nasser
    • , Thouis R. Jones
    • , Glen Munson
    • , Drew T. Bergman
    • , Vidya Subramanian
    • , Sharon R. Grossman
    • , Rockwell Anyoha
    • , Benjamin R. Doughty
    • , Tejal A. Patwardhan
    • , Tung H. Nguyen
    • , Michael Kane
    • , Elizabeth M. Perez
    • , Neva C. Durand
    • , Caleb A. Lareau
    • , Elena K. Stamenova
    • , Erez Lieberman Aiden
    • , Eric S. Lander
    •  & Jesse M. Engreitz
  • Letter |

    Genome-wide analysis of venous thromboembolism identifies 22 new risk loci and facilitates construction of a polygenic risk score. Comparison to arterial vascular disease highlights shared pathophysiology and potential therapeutic strategies.

    • Derek Klarin
    • , Emma Busenkell
    • , Renae Judy
    • , Julie Lynch
    • , Michael Levin
    • , Jeffery Haessler
    • , Krishna Aragam
    • , Mark Chaffin
    • , Mary Haas
    • , Sara Lindström
    • , Themistocles L. Assimes
    • , Jie Huang
    • , Kyung Min Lee
    • , Qing Shao
    • , Jennifer E. Huffman
    • , Christopher Kabrhel
    • , Yunfeng Huang
    • , Yan V. Sun
    • , Marijana Vujkovic
    • , Danish Saleheen
    • , Donald R. Miller
    • , Peter Reaven
    • , Scott DuVall
    • , William E. Boden
    • , Saiju Pyarajan
    • , Alex P. Reiner
    • , David-Alexandre Trégouët
    • , Peter Henke
    • , Charles Kooperberg
    • , J. Michael Gaziano
    • , John Concato
    • , Daniel J. Rader
    • , Kelly Cho
    • , Kyong-Mi Chang
    • , Peter W. F. Wilson
    • , Nicholas L. Smith
    • , Christopher J. O’Donnell
    • , Philip S. Tsao
    • , Sekar Kathiresan
    • , Andrea Obi
    • , Scott M. Damrauer
    •  & Pradeep Natarajan
  • Letter |

    Genome-wide analyses identify variants near HDAC9 associated with abdominal aortic calcification and other cardiovascular phenotypes. Functional work shows that HDAC9 promotes an osteogenic vascular smooth muscle cell phenotype, enhancing calcification and reducing contractility.

    • Rajeev Malhotra
    • , Andreas C. Mauer
    • , Christian L. Lino Cardenas
    • , Xiuqing Guo
    • , Jie Yao
    • , Xiaoling Zhang
    • , Florian Wunderer
    • , Albert V. Smith
    • , Quenna Wong
    • , Sonali Pechlivanis
    • , Shih-Jen Hwang
    • , Judy Wang
    • , Lingyi Lu
    • , Christopher J. Nicholson
    • , Georgia Shelton
    • , Mary D. Buswell
    • , Hanna J. Barnes
    • , Haakon H. Sigurslid
    • , Charles Slocum
    • , Caitlin O’ Rourke
    • , David K. Rhee
    • , Aranya Bagchi
    • , Sagar U. Nigwekar
    • , Emmanuel S. Buys
    • , Catherine Y. Campbell
    • , Tamara Harris
    • , Matthew Budoff
    • , Michael H. Criqui
    • , Jerome I. Rotter
    • , Andrew D. Johnson
    • , Ci Song
    • , Nora Franceschini
    • , Stephanie Debette
    • , Udo Hoffmann
    • , Hagen Kälsch
    • , Markus M. Nöthen
    • , Sigurdur Sigurdsson
    • , Barry I. Freedman
    • , Donald W. Bowden
    • , Karl-Heinz Jöckel
    • , Susanne Moebus
    • , Raimund Erbel
    • , Mary F. Feitosa
    • , Vilmundur Gudnason
    • , George Thanassoulis
    • , Warren M. Zapol
    • , Mark E. Lindsay
    • , Donald B. Bloch
    • , Wendy S. Post
    •  & Christopher J. O’Donnell
  • Letter |

    Mapping long-range chromatin interactions in 27 human cell/tissue types identifies candidate target genes of 70,329 putative regulatory elements. Further analysis suggests potential regulatory function for 27,325 noncoding variants associated with 2,117 traits and diseases.

    • Inkyung Jung
    • , Anthony Schmitt
    • , Yarui Diao
    • , Andrew J. Lee
    • , Tristin Liu
    • , Dongchan Yang
    • , Catherine Tan
    • , Junghyun Eom
    • , Marilynn Chan
    • , Sora Chee
    • , Zachary Chiang
    • , Changyoun Kim
    • , Eliezer Masliah
    • , Cathy L. Barr
    • , Bin Li
    • , Samantha Kuan
    • , Dongsup Kim
    •  & Bing Ren
  • Letter |

    Genomic analysis of 906 Clostridium difficile strains shows that this enteropathogen is undergoing speciation, which is linked to the selection of genes involved in sporulation and in the metabolism of simple dietary sugars.

    • Nitin Kumar
    • , Hilary P. Browne
    • , Elisa Viciani
    • , Samuel C. Forster
    • , Simon Clare
    • , Katherine Harcourt
    • , Mark D. Stares
    • , Gordon Dougan
    • , Derek J. Fairley
    • , Paul Roberts
    • , Munir Pirmohamed
    • , Martha R. J. Clokie
    • , Mie Birgitte Frid Jensen
    • , Katherine R. Hargreaves
    • , Margaret Ip
    • , Lothar H. Wieler
    • , Christian Seyboldt
    • , Torbjörn Norén
    • , Thomas V. Riley
    • , Ed J. Kuijper
    • , Brendan W. Wren
    •  & Trevor D. Lawley
  • Letter |

    A mutation in RAS oncogene family-like 3 (RABL3) is discovered in a family with multiple cases of pancreatic cancer. Zebrafish modeling and biochemical approaches suggest that truncated RABL3 elevates KRAS activity via accelerated prenylation.

    • Sahar Nissim
    • , Ignaty Leshchiner
    • , Joseph D. Mancias
    • , Matthew B. Greenblatt
    • , Ophélia Maertens
    • , Christopher A. Cassa
    • , Jill A. Rosenfeld
    • , Andrew G. Cox
    • , John Hedgepeth
    • , Julia I. Wucherpfennig
    • , Andrew J. Kim
    • , Jake E. Henderson
    • , Patrick Gonyo
    • , Anthony Brandt
    • , Ellen Lorimer
    • , Bethany Unger
    • , Jeremy W. Prokop
    • , Jerry R. Heidel
    • , Xiao-Xu Wang
    • , Chinedu I. Ukaegbu
    • , Benjamin C. Jennings
    • , Joao A. Paulo
    • , Sebastian Gableske
    • , Carol A. Fierke
    • , Gad Getz
    • , Shamil R. Sunyaev
    • , J. Wade Harper
    • , Karen Cichowski
    • , Alec C. Kimmelman
    • , Yariv Houvras
    • , Sapna Syngal
    • , Carol Williams
    •  & Wolfram Goessling
  • Letter |

    Long-read sequencing identifies a GGC repeat expansion in NOTCH2NLC that is associated with neuronal intranuclear inclusion disease, a progressive neurodegenerative disorder. The expansion results in abnormal anti-sense transcripts that could contribute to disease pathogenesis.

    • Jun Sone
    • , Satomi Mitsuhashi
    • , Atsushi Fujita
    • , Takeshi Mizuguchi
    • , Kohei Hamanaka
    • , Keiko Mori
    • , Haruki Koike
    • , Akihiro Hashiguchi
    • , Hiroshi Takashima
    • , Hiroshi Sugiyama
    • , Yutaka Kohno
    • , Yoshihisa Takiyama
    • , Kengo Maeda
    • , Hiroshi Doi
    • , Shigeru Koyano
    • , Hideyuki Takeuchi
    • , Michi Kawamoto
    • , Nobuo Kohara
    • , Tetsuo Ando
    • , Toshiaki Ieda
    • , Yasushi Kita
    • , Norito Kokubun
    • , Yoshio Tsuboi
    • , Kazutaka Katoh
    • , Yoshihiro Kino
    • , Masahisa Katsuno
    • , Yasushi Iwasaki
    • , Mari Yoshida
    • , Fumiaki Tanaka
    • , Ikuo K. Suzuki
    • , Martin C. Frith
    • , Naomichi Matsumoto
    •  & Gen Sobue
  • Letter |

    Genome-wide analyses identify eight independent loci associated with anorexia nervosa. Genetic correlations implicate both psychiatric and metabolic components in the etiology of this disorder, even after adjusting for the effects of common variants associated with body mass index.

    • Hunna J. Watson
    • , Zeynep Yilmaz
    • , Laura M. Thornton
    • , Christopher Hübel
    • , Jonathan R. I. Coleman
    • , Héléna A. Gaspar
    • , Julien Bryois
    • , Anke Hinney
    • , Virpi M. Leppä
    • , Manuel Mattheisen
    • , Sarah E. Medland
    • , Stephan Ripke
    • , Shuyang Yao
    • , Paola Giusti-Rodríguez
    • , Ken B. Hanscombe
    • , Kirstin L. Purves
    • , Roger A. H. Adan
    • , Lars Alfredsson
    • , Tetsuya Ando
    • , Ole A. Andreassen
    • , Jessica H. Baker
    • , Wade H. Berrettini
    • , Ilka Boehm
    • , Claudette Boni
    • , Vesna Boraska Perica
    • , Katharina Buehren
    • , Roland Burghardt
    • , Matteo Cassina
    • , Sven Cichon
    • , Maurizio Clementi
    • , Roger D. Cone
    • , Philippe Courtet
    • , Scott Crow
    • , James J. Crowley
    • , Unna N. Danner
    • , Oliver S. P. Davis
    • , Martina de Zwaan
    • , George Dedoussis
    • , Daniela Degortes
    • , Janiece E. DeSocio
    • , Danielle M. Dick
    • , Dimitris Dikeos
    • , Christian Dina
    • , Monika Dmitrzak-Weglarz
    • , Elisa Docampo
    • , Laramie E. Duncan
    • , Karin Egberts
    • , Stefan Ehrlich
    • , Geòrgia Escaramís
    • , Tõnu Esko
    • , Xavier Estivill
    • , Anne Farmer
    • , Angela Favaro
    • , Fernando Fernández-Aranda
    • , Manfred M. Fichter
    • , Krista Fischer
    • , Manuel Föcker
    • , Lenka Foretova
    • , Andreas J. Forstner
    • , Monica Forzan
    • , Christopher S. Franklin
    • , Steven Gallinger
    • , Ina Giegling
    • , Johanna Giuranna
    • , Fragiskos Gonidakis
    • , Philip Gorwood
    • , Monica Gratacos Mayora
    • , Sébastien Guillaume
    • , Yiran Guo
    • , Hakon Hakonarson
    • , Konstantinos Hatzikotoulas
    • , Joanna Hauser
    • , Johannes Hebebrand
    • , Sietske G. Helder
    • , Stefan Herms
    • , Beate Herpertz-Dahlmann
    • , Wolfgang Herzog
    • , Laura M. Huckins
    • , James I. Hudson
    • , Hartmut Imgart
    • , Hidetoshi Inoko
    • , Vladimir Janout
    • , Susana Jiménez-Murcia
    • , Antonio Julià
    • , Gursharan Kalsi
    • , Deborah Kaminská
    • , Jaakko Kaprio
    • , Leila Karhunen
    • , Andreas Karwautz
    • , Martien J. H. Kas
    • , James L. Kennedy
    • , Anna Keski-Rahkonen
    • , Kirsty Kiezebrink
    • , Youl-Ri Kim
    • , Lars Klareskog
    • , Kelly L. Klump
    • , Gun Peggy S. Knudsen
    • , Maria C. La Via
    • , Stephanie Le Hellard
    • , Robert D. Levitan
    • , Dong Li
    • , Lisa Lilenfeld
    • , Bochao Danae Lin
    • , Jolanta Lissowska
    • , Jurjen Luykx
    • , Pierre J. Magistretti
    • , Mario Maj
    • , Katrin Mannik
    • , Sara Marsal
    • , Christian R. Marshall
    • , Morten Mattingsdal
    • , Sara McDevitt
    • , Peter McGuffin
    • , Andres Metspalu
    • , Ingrid Meulenbelt
    • , Nadia Micali
    • , Karen Mitchell
    • , Alessio Maria Monteleone
    • , Palmiero Monteleone
    • , Melissa A. Munn-Chernoff
    • , Benedetta Nacmias
    • , Marie Navratilova
    • , Ioanna Ntalla
    • , Julie K. O’Toole
    • , Roel A. Ophoff
    • , Leonid Padyukov
    • , Aarno Palotie
    • , Jacques Pantel
    • , Hana Papezova
    • , Dalila Pinto
    • , Raquel Rabionet
    • , Anu Raevuori
    • , Nicolas Ramoz
    • , Ted Reichborn-Kjennerud
    • , Valdo Ricca
    • , Samuli Ripatti
    • , Franziska Ritschel
    • , Marion Roberts
    • , Alessandro Rotondo
    • , Dan Rujescu
    • , Filip Rybakowski
    • , Paolo Santonastaso
    • , André Scherag
    • , Stephen W. Scherer
    • , Ulrike Schmidt
    • , Nicholas J. Schork
    • , Alexandra Schosser
    • , Jochen Seitz
    • , Lenka Slachtova
    • , P. Eline Slagboom
    • , Margarita C. T. Slof-Op ‘t Landt
    • , Agnieszka Slopien
    • , Sandro Sorbi
    • , Beata Świątkowska
    • , Jin P. Szatkiewicz
    • , Ioanna Tachmazidou
    • , Elena Tenconi
    • , Alfonso Tortorella
    • , Federica Tozzi
    • , Janet Treasure
    • , Artemis Tsitsika
    • , Marta Tyszkiewicz-Nwafor
    • , Konstantinos Tziouvas
    • , Annemarie A. van Elburg
    • , Eric F. van Furth
    • , Gudrun Wagner
    • , Esther Walton
    • , Elisabeth Widen
    • , Eleftheria Zeggini
    • , Stephanie Zerwas
    • , Stephan Zipfel
    • , Andrew W. Bergen
    • , Joseph M. Boden
    • , Harry Brandt
    • , Steven Crawford
    • , Katherine A. Halmi
    • , L. John Horwood
    • , Craig Johnson
    • , Allan S. Kaplan
    • , Walter H. Kaye
    • , James E. Mitchell
    • , Catherine M. Olsen
    • , John F. Pearson
    • , Nancy L. Pedersen
    • , Michael Strober
    • , Thomas Werge
    • , David C. Whiteman
    • , D. Blake Woodside
    • , Garret D. Stuber
    • , Scott Gordon
    • , Jakob Grove
    • , Anjali K. Henders
    • , Anders Juréus
    • , Katherine M. Kirk
    • , Janne T. Larsen
    • , Richard Parker
    • , Liselotte Petersen
    • , Jennifer Jordan
    • , Martin Kennedy
    • , Grant W. Montgomery
    • , Tracey D. Wade
    • , Andreas Birgegård
    • , Paul Lichtenstein
    • , Claes Norring
    • , Mikael Landén
    • , Nicholas G. Martin
    • , Preben Bo Mortensen
    • , Patrick F. Sullivan
    • , Gerome Breen
    •  & Cynthia M. Bulik
  • Letter |

    A genetics-led translational approach integrating functional genomic predictors, knowledge of network connectivity and immune ontologies defines the drug target prioritization landscape for 30 immune traits at the gene and pathway level.

    • Hai Fang
    • , Georg Beckmann
    • , Chas Bountra
    • , Paul Bowness
    • , Nicola Burgess-Brown
    • , Liz Carpenter
    • , Liye Chen
    • , David Damerell
    • , Ursula Egner
    • , Hai Fang
    • , Ryo Fujii
    • , Trevor Howe
    • , Per-Johan Jakobsson
    • , Andreas Katopodis
    • , Julian C. Knight
    • , Brian D. Marsden
    • , Julie De Martino
    • , Gstaiger Matthias
    • , Gilean McVean
    • , Anke Mueller-Fahrnow
    • , Anders Mälarstig
    • , Chris A. O’Callaghan
    • , Nils Ostermann
    • , Jesus R. Paez-cortez
    • , Pieter J. Peeters
    • , Florian Prinz
    • , Patricia Soulard
    • , Michael Sundström
    • , Chiori Yabuki
    • , Jaromir Vlach
    • , Hans De Wolf
    • , Bogdan Knezevic
    • , Katie L. Burnham
    • , Julie Osgood
    • , Anna Sanniti
    • , Alicia Lledó Lara
    • , Silva Kasela
    • , Stephane De Cesco
    • , Jörg K. Wegner
    • , Lahiru Handunnetthi
    • , Fiona E. McCann
    • , Liye Chen
    • , Takuya Sekine
    • , Paul E. Brennan
    • , Brian D. Marsden
    • , David Damerell
    • , Chris A. O’Callaghan
    • , Chas Bountra
    • , Paul Bowness
    • , Yvonne Sundström
    • , Lili Milani
    • , Louise Berg
    • , Hinrich W. Göhlmann
    • , Pieter J. Peeters
    • , Benjamin P. Fairfax
    • , Michael Sundström
    •  & Julian C. Knight
  • Letter |

    Analysis of whole-exome sequencing data from 2,343 individuals with autism spectrum disorder compared to 5,852 unaffected individuals demonstrates an excess of biallelic, autosomal mutations for both loss-of-function and damaging missense variants.

    • Ryan N. Doan
    • , Elaine T. Lim
    • , Silvia De Rubeis
    • , Catalina Betancur
    • , David J. Cutler
    • , Andreas G. Chiocchetti
    • , Lynne M. Overman
    • , Aubrie Soucy
    • , Susanne Goetze
    • , Christine M. Freitag
    • , Mark J. Daly
    • , Christopher A. Walsh
    • , Joseph D. Buxbaum
    •  & Timothy W. Yu
  • Letter |

    Genetic studies using map-based cloning, gene editing, RNA interference, haplotyping and association analyses identify a deletion in TaHRC as a key determinant of Fhb1-mediated resistance to Fusarium head blight in wheat.

    • Zhenqi Su
    • , Amy Bernardo
    • , Bin Tian
    • , Hui Chen
    • , Shan Wang
    • , Hongxiang Ma
    • , Shibin Cai
    • , Dongtao Liu
    • , Dadong Zhang
    • , Tao Li
    • , Harold Trick
    • , Paul St. Amand
    • , Jianming Yu
    • , Zengyan Zhang
    •  & Guihua Bai
  • Letter |

    Genetic mapping and functional studies show that mutation of a histidine-rich calcium-binding-protein gene at the Fhb1 locus confers resistance to Fusarium head blight in wheat. Notably, transgenic plants expressing the R allele show enhanced resistance to infection.

    • Guoqiang Li
    • , Jiyang Zhou
    • , Haiyan Jia
    • , Zhongxia Gao
    • , Min Fan
    • , Yanjun Luo
    • , Panting Zhao
    • , Shulin Xue
    • , Na Li
    • , Yang Yuan
    • , Shengwei Ma
    • , Zhongxin Kong
    • , Li Jia
    • , Xia An
    • , Ge Jiang
    • , Wenxing Liu
    • , Wenjin Cao
    • , Rongrong Zhang
    • , Jicai Fan
    • , Xiaowu Xu
    • , Yanfang Liu
    • , Qianqian Kong
    • , Shouhang Zheng
    • , Yao Wang
    • , Bin Qin
    • , Shouyang Cao
    • , Yunxiao Ding
    • , Jinxing Shi
    • , Haisheng Yan
    • , Xin Wang
    • , Congfu Ran
    •  & Zhengqiang Ma
  • Letter |

    Phosphorylation of histone H3.3 at serine 31 by CHK1 is shown to stimulate activity of the acetyltransferase p300 in trans. Depletion of histone H3.3 in embryonic stem cells reduces enhancer acetylation during differentiation.

    • Sara Martire
    • , Aishwarya A. Gogate
    • , Amanda Whitmill
    • , Amanuel Tafessu
    • , Jennifer Nguyen
    • , Yu-Ching Teng
    • , Melodi Tastemel
    •  & Laura A. Banaszynski
  • Letter |

    The authors present a new genomic prediction method for maize germplasm evaluation under genotype × environment interaction, in which genotype × environment interaction of grain yield components is modeled as genotypic sensitivity to environmental drivers.

    • Emilie J. Millet
    • , Willem Kruijer
    • , Aude Coupel-Ledru
    • , Santiago Alvarez Prado
    • , Llorenç Cabrera-Bosquet
    • , Sébastien Lacube
    • , Alain Charcosset
    • , Claude Welcker
    • , Fred van Eeuwijk
    •  & François Tardieu
  • Letter |

    A study of a stem cell receptor–ligand signaling module across tomato, maize and Arabidopsis identifies different genetic mechanisms of compensation that contribute to homeostasis.

    • Daniel Rodriguez-Leal
    • , Cao Xu
    • , Choon-Tak Kwon
    • , Cara Soyars
    • , Edgar Demesa-Arevalo
    • , Jarrett Man
    • , Lei Liu
    • , Zachary H. Lemmon
    • , Daniel S. Jones
    • , Joyce Van Eck
    • , David P. Jackson
    • , Madelaine E. Bartlett
    • , Zachary L. Nimchuk
    •  & Zachary B. Lippman
  • Letter |

    The authors show that the transcription factors HNF4A and HNF4G regulate the transcriptome of the intestinal epithelium. HNF4 factors cooperate with BMP/SMAD signaling to promote enterocyte identity.

    • Lei Chen
    • , Natalie H. Toke
    • , Shirley Luo
    • , Roshan P. Vasoya
    • , Robert L. Fullem
    • , Aditya Parthasarathy
    • , Ansu O. Perekatt
    •  & Michael P. Verzi
  • Letter |

    A pan-cancer analysis identifies 129 transposable-element-driven promoter-activation events involving 106 oncogenes. At the AluJb-LIN28B locus, deletion of the transposable element eliminates oncogene expression.

    • Hyo Sik Jang
    • , Nakul M. Shah
    • , Alan Y. Du
    • , Zea Z. Dailey
    • , Erica C. Pehrsson
    • , Paula M. Godoy
    • , David Zhang
    • , Daofeng Li
    • , Xiaoyun Xing
    • , Sungsu Kim
    • , David O’Donnell
    • , Jeffrey I. Gordon
    •  & Ting Wang
  • Letter |

    Generation of a library of 62,389 mapped insertion mutants for the unicellular alga Chlamydomonas reinhardtii enables screening for genes required for photosynthesis and the identification of 303 candidate genes.

    • Xiaobo Li
    • , Weronika Patena
    • , Friedrich Fauser
    • , Robert E. Jinkerson
    • , Shai Saroussi
    • , Moritz T. Meyer
    • , Nina Ivanova
    • , Jacob M. Robertson
    • , Rebecca Yue
    • , Ru Zhang
    • , Josep Vilarrasa-Blasi
    • , Tyler M. Wittkopp
    • , Silvia Ramundo
    • , Sean R. Blum
    • , Audrey Goh
    • , Matthew Laudon
    • , Tharan Srikumar
    • , Paul A. Lefebvre
    • , Arthur R. Grossman
    •  & Martin C. Jonikas
  • Letter |

    This study uses SMARCA2/4-mutant variants to define catalytic activity–dependent and catalytic activity–independent contributions of the ATPase module to the targeting of BAF and PBAF complexes genome-wide.

    • Joshua Pan
    • , Zachary M. McKenzie
    • , Andrew R. D’Avino
    • , Nazar Mashtalir
    • , Caleb A. Lareau
    • , Roodolph St. Pierre
    • , Lu Wang
    • , Ali Shilatifard
    •  & Cigall Kadoch
  • Letter |

    Genome-wide association analyses identify 57 loci associated with insomnia symptoms and provide evidence of shared genetic architecture between insomnia and cardiometabolic, behavioral, psychiatric and reproductive traits.

    • Jacqueline M. Lane
    • , Samuel E. Jones
    • , Hassan S. Dashti
    • , Andrew R. Wood
    • , Krishna G. Aragam
    • , Vincent T. van Hees
    • , Linn B. Strand
    • , Bendik S. Winsvold
    • , Heming Wang
    • , Jack Bowden
    • , Yanwei Song
    • , Krunal Patel
    • , Simon G. Anderson
    • , Robin N. Beaumont
    • , David A. Bechtold
    • , Brian E. Cade
    • , Mary Haas
    • , Sekar Kathiresan
    • , Max A. Little
    • , Annemarie I. Luik
    • , Andrew S. Loudon
    • , Shaun Purcell
    • , Rebecca C. Richmond
    • , Frank A. J. L. Scheer
    • , Barbara Schormair
    • , Jessica Tyrrell
    • , John W. Winkelman
    • , Juliane Winkelmann
    • , Amy E. Martinsen
    • , Anne H. Skogholt
    • , Ben Brumpton
    • , Bendik S. Winsvold
    • , Børge Sivertsen
    • , Cristen J. Willer
    • , Daniela Bragantini
    • , Håvard Kallestad
    • , Imre Janszky
    • , Ismail C. Guzey
    • , John-Anker Zwart
    • , Jonas B. Nielsen
    • , Kristian B. Nilsen
    • , Kristian Hveem
    • , Lars Fritsche
    • , Linda M. Pedersen
    • , Linn B. Strand
    • , Maiken E. Gabrielsen
    • , Marianne B. Johnsen
    • , Marie U. Lie
    • , Morten Engstrøm
    • , Trond Sand
    • , Wei Zhou
    • , Kristian Hveem
    • , Chen Zhao
    • , Jonas B. Nielsen
    • , Cristen J. Willer
    • , Susan Redline
    • , Kai Spiegelhalder
    • , Simon D. Kyle
    • , David W. Ray
    • , John-Anker Zwart
    • , Ben Brumpton
    • , Timothy M. Frayling
    • , Deborah A. Lawlor
    • , Martin K. Rutter
    • , Michael N. Weedon
    •  & Richa Saxena
  • Letter |

    Mendelian randomization analyses using genotyping data, gut metagenomic sequence and fecal short-chain-fatty-acid levels from 952 individuals combined with GWAS data show evidence of a causal effect of the gut microbiome on metabolic traits.

    • Serena Sanna
    • , Natalie R. van Zuydam
    • , Anubha Mahajan
    • , Alexander Kurilshikov
    • , Arnau Vich Vila
    • , Urmo Võsa
    • , Zlatan Mujagic
    • , Ad A. M. Masclee
    • , Daisy M. A. E. Jonkers
    • , Marije Oosting
    • , Leo A. B. Joosten
    • , Mihai G. Netea
    • , Lude Franke
    • , Alexandra Zhernakova
    • , Jingyuan Fu
    • , Cisca Wijmenga
    •  & Mark I. McCarthy
  • Letter |

    The authors transcriptionally profiled postmortem retinas from 453 age-related macular degeneration (AMD) cases and controls. Integration of AMD GWAS with eQTL analysis and TWAS identified several AMD-associated genes.

    • Rinki Ratnapriya
    • , Olukayode A. Sosina
    • , Margaret R. Starostik
    • , Madeline Kwicklis
    • , Rebecca J. Kapphahn
    • , Lars G. Fritsche
    • , Ashley Walton
    • , Marios Arvanitis
    • , Linn Gieser
    • , Alexandra Pietraszkiewicz
    • , Sandra R. Montezuma
    • , Emily Y. Chew
    • , Alexis Battle
    • , Gonçalo R. Abecasis
    • , Deborah A. Ferrington
    • , Nilanjan Chatterjee
    •  & Anand Swaroop
  • Letter |

    Genome-wide association analyses identify 28 new susceptibility loci for type 2 diabetes in the Japanese population. Transethnic comparisons highlight the key role of beta cell dysfunction in type 2 diabetes across different ancestry groups.

    • Ken Suzuki
    • , Masato Akiyama
    • , Kazuyoshi Ishigaki
    • , Masahiro Kanai
    • , Jun Hosoe
    • , Nobuhiro Shojima
    • , Atsushi Hozawa
    • , Aya Kadota
    • , Kiyonori Kuriki
    • , Mariko Naito
    • , Kozo Tanno
    • , Yasushi Ishigaki
    • , Makoto Hirata
    • , Koichi Matsuda
    • , Nakao Iwata
    • , Masashi Ikeda
    • , Norie Sawada
    • , Taiki Yamaji
    • , Motoki Iwasaki
    • , Shiro Ikegawa
    • , Shiro Maeda
    • , Yoshinori Murakami
    • , Kenji Wakai
    • , Shoichiro Tsugane
    • , Makoto Sasaki
    • , Masayuki Yamamoto
    • , Yukinori Okada
    • , Michiaki Kubo
    • , Yoichiro Kamatani
    • , Momoko Horikoshi
    • , Toshimasa Yamauchi
    •  & Takashi Kadowaki
  • Letter |

    Genome-wide meta-analysis of UK Biobank and arcOGEN (77,052 cases and 378,169 controls) identifies 52 new osteoarthritis risk loci. Integrated eQTL colocalization, fine-mapping, and rare-disease data identify putative effector genes for osteoarthritis.

    • Ioanna Tachmazidou
    • , Konstantinos Hatzikotoulas
    • , Lorraine Southam
    • , Jorge Esparza-Gordillo
    • , Valeriia Haberland
    • , Jie Zheng
    • , Toby Johnson
    • , Mine Koprulu
    • , Eleni Zengini
    • , Julia Steinberg
    • , Jeremy M. Wilkinson
    • , Sahir Bhatnagar
    • , Joshua D. Hoffman
    • , Natalie Buchan
    • , Dániel Süveges
    • , Laura Yerges-Armstrong
    • , George Davey Smith
    • , Tom R. Gaunt
    • , Robert A. Scott
    • , Linda C. McCarthy
    •  & Eleftheria Zeggini
  • Letter |

    Association studies of up to 1.2 million individuals identify 566 genetic variants in 406 loci associated with tobacco use and addiction (initiation, cessation, and heaviness) as well as alcohol use, with 150 loci showing pleiotropic association.

    • Mengzhen Liu
    • , Yu Jiang
    • , Robbee Wedow
    • , Yue Li
    • , David M. Brazel
    • , Fang Chen
    • , Gargi Datta
    • , Jose Davila-Velderrain
    • , Daniel McGuire
    • , Chao Tian
    • , Xiaowei Zhan
    • , Michelle Agee
    • , Babak Alipanahi
    • , Adam Auton
    • , Robert K. Bell
    • , Katarzyna Bryc
    • , Sarah L. Elson
    • , Pierre Fontanillas
    • , Nicholas A. Furlotte
    • , David A. Hinds
    • , Bethann S. Hromatka
    • , Karen E. Huber
    • , Aaron Kleinman
    • , Nadia K. Litterman
    • , Matthew H. McIntyre
    • , Joanna L. Mountain
    • , Carrie A. M. Northover
    • , J. Fah Sathirapongsasuti
    • , Olga V. Sazonova
    • , Janie F. Shelton
    • , Suyash Shringarpure
    • , Chao Tian
    • , Joyce Y. Tung
    • , Vladimir Vacic
    • , Catherine H. Wilson
    • , Steven J. Pitts
    • , Amy Mitchell
    • , Anne Heidi Skogholt
    • , Bendik S. Winsvold
    • , Børge Sivertsen
    • , Eystein Stordal
    • , Gunnar Morken
    • , Håvard Kallestad
    • , Ingrid Heuch
    • , John-Anker Zwart
    • , Katrine Kveli Fjukstad
    • , Linda M. Pedersen
    • , Maiken Elvestad Gabrielsen
    • , Marianne Bakke Johnsen
    • , Marit Skrove
    • , Marit Sæbø Indredavik
    • , Ole Kristian Drange
    • , Ottar Bjerkeset
    • , Sigrid Børte
    • , Synne Øien Stensland
    • , Hélène Choquet
    • , Anna R. Docherty
    • , Jessica D. Faul
    • , Johanna R. Foerster
    • , Lars G. Fritsche
    • , Maiken Elvestad Gabrielsen
    • , Scott D. Gordon
    • , Jeffrey Haessler
    • , Jouke-Jan Hottenga
    • , Hongyan Huang
    • , Seon-Kyeong Jang
    • , Philip R. Jansen
    • , Yueh Ling
    • , Reedik Mägi
    • , Nana Matoba
    • , George McMahon
    • , Antonella Mulas
    • , Valeria Orrù
    • , Teemu Palviainen
    • , Anita Pandit
    • , Gunnar W. Reginsson
    • , Anne Heidi Skogholt
    • , Jennifer A. Smith
    • , Amy E. Taylor
    • , Constance Turman
    • , Gonneke Willemsen
    • , Hannah Young
    • , Kendra A. Young
    • , Gregory J. M. Zajac
    • , Wei Zhao
    • , Wei Zhou
    • , Gyda Bjornsdottir
    • , Jason D. Boardman
    • , Michael Boehnke
    • , Dorret I. Boomsma
    • , Chu Chen
    • , Francesco Cucca
    • , Gareth E. Davies
    • , Charles B. Eaton
    • , Marissa A. Ehringer
    • , Tõnu Esko
    • , Edoardo Fiorillo
    • , Nathan A. Gillespie
    • , Daniel F. Gudbjartsson
    • , Toomas Haller
    • , Kathleen Mullan Harris
    • , Andrew C. Heath
    • , John K. Hewitt
    • , Ian B. Hickie
    • , John E. Hokanson
    • , Christian J. Hopfer
    • , David J. Hunter
    • , William G. Iacono
    • , Eric O. Johnson
    • , Yoichiro Kamatani
    • , Sharon L. R. Kardia
    • , Matthew C. Keller
    • , Manolis Kellis
    • , Charles Kooperberg
    • , Peter Kraft
    • , Kenneth S. Krauter
    • , Markku Laakso
    • , Penelope A. Lind
    • , Anu Loukola
    • , Sharon M. Lutz
    • , Pamela A. F. Madden
    • , Nicholas G. Martin
    • , Matt McGue
    • , Matthew B. McQueen
    • , Sarah E. Medland
    • , Andres Metspalu
    • , Karen L. Mohlke
    • , Jonas B. Nielsen
    • , Yukinori Okada
    • , Ulrike Peters
    • , Tinca J. C. Polderman
    • , Danielle Posthuma
    • , Alexander P. Reiner
    • , John P. Rice
    • , Eric Rimm
    • , Richard J. Rose
    • , Valgerdur Runarsdottir
    • , Michael C. Stallings
    • , Alena Stančáková
    • , Hreinn Stefansson
    • , Khanh K. Thai
    • , Hilary A. Tindle
    • , Thorarinn Tyrfingsson
    • , Tamara L. Wall
    • , David R. Weir
    • , Constance Weisner
    • , John B. Whitfield
    • , Bendik Slagsvold Winsvold
    • , Jie Yin
    • , Luisa Zuccolo
    • , Laura J. Bierut
    • , Kristian Hveem
    • , James J. Lee
    • , Marcus R. Munafò
    • , Nancy L. Saccone
    • , Cristen J. Willer
    • , Marilyn C. Cornelis
    • , Sean P. David
    • , David A. Hinds
    • , Eric Jorgenson
    • , Jaakko Kaprio
    • , Jerry A. Stitzel
    • , Kari Stefansson
    • , Thorgeir E. Thorgeirsson
    • , Gonçalo Abecasis
    • , Dajiang J. Liu
    •  & Scott Vrieze
  • Letter |

    Analysis of advanced cancer patients treated with immune-checkpoint inhibitors shows that tumor mutational burden, as assessed by targeted next-generation sequencing, predicts survival after immunotherapy across multiple cancer types.

    • Robert M. Samstein
    • , Chung-Han Lee
    • , Alexander N. Shoushtari
    • , Matthew D. Hellmann
    • , Ronglai Shen
    • , Yelena Y. Janjigian
    • , David A. Barron
    • , Ahmet Zehir
    • , Emmet J. Jordan
    • , Antonio Omuro
    • , Thomas J. Kaley
    • , Sviatoslav M. Kendall
    • , Robert J. Motzer
    • , A. Ari Hakimi
    • , Martin H. Voss
    • , Paul Russo
    • , Jonathan Rosenberg
    • , Gopa Iyer
    • , Bernard H. Bochner
    • , Dean F. Bajorin
    • , Hikmat A. Al-Ahmadie
    • , Jamie E. Chaft
    • , Charles M. Rudin
    • , Gregory J. Riely
    • , Shrujal Baxi
    • , Alan L. Ho
    • , Richard J. Wong
    • , David G. Pfister
    • , Jedd D. Wolchok
    • , Christopher A. Barker
    • , Philip H. Gutin
    • , Cameron W. Brennan
    • , Viviane Tabar
    • , Ingo K. Mellinghoff
    • , Lisa M. DeAngelis
    • , Charlotte E. Ariyan
    • , Nancy Lee
    • , William D. Tap
    • , Mrinal M. Gounder
    • , Sandra P. D’Angelo
    • , Leonard Saltz
    • , Zsofia K. Stadler
    • , Howard I. Scher
    • , Jose Baselga
    • , Pedram Razavi
    • , Christopher A. Klebanoff
    • , Rona Yaeger
    • , Neil H. Segal
    • , Geoffrey Y. Ku
    • , Ronald P. DeMatteo
    • , Marc Ladanyi
    • , Naiyer A. Rizvi
    • , Michael F. Berger
    • , Nadeem Riaz
    • , David B. Solit
    • , Timothy A. Chan
    •  & Luc G. T. Morris
  • Letter |

    Genomic analysis of 151 diploid potatoes and three potato populations produced by self-crossing identifies 344,831 deleterious substitutions and 15 genomic regions with severe segregation distortions, providing the basis for genome design of potato inbred lines.

    • Chunzhi Zhang
    • , Pei Wang
    • , Die Tang
    • , Zhongmin Yang
    • , Fei Lu
    • , Jianjian Qi
    • , Nilesh R. Tawari
    • , Yi Shang
    • , Canhui Li
    •  & Sanwen Huang
  • Letter |

    GADD45A directly binds to R-loops and mediates local DNA demethylation by recruiting TET1. lncRNA-mediated formation of R-loops at the promoter of the tumor suppressor TCF21 triggers GADD45A binding, demethylation and expression.

    • Khelifa Arab
    • , Emil Karaulanov
    • , Michael Musheev
    • , Philipp Trnka
    • , Andrea Schäfer
    • , Ingrid Grummt
    •  & Christof Niehrs
  • Letter |

    Activating HER2 mutations are shown to confer resistance to ER-directed therapies in patients with ER+ metastatic breast cancer. Drug resistance caused by HER2 mutations was overcome by combining ER-directed therapy with a HER2 kinase inhibitor.

    • Utthara Nayar
    • , Ofir Cohen
    • , Christian Kapstad
    • , Michael S. Cuoco
    • , Adrienne G. Waks
    • , Seth A. Wander
    • , Corrie Painter
    • , Samuel Freeman
    • , Nicole S. Persky
    • , Lori Marini
    • , Karla Helvie
    • , Nelly Oliver
    • , Orit Rozenblatt-Rosen
    • , Cynthia X. Ma
    • , Aviv Regev
    • , Eric P. Winer
    • , Nancy U. Lin
    •  & Nikhil Wagle
  • Letter |

    Analysis of mutational asymmetry with respect to the direction of replication and transcription suggests that error-prone damage bypass on the lagging strand has a major role in human germline and cancer mutations.

    • Vladimir B. Seplyarskiy
    • , Evgeny E. Akkuratov
    • , Natalia Akkuratova
    • , Maria A. Andrianova
    • , Sergey I. Nikolaev
    • , Georgii A. Bazykin
    • , Igor Adameyko
    •  & Shamil R. Sunyaev
  • Letter
    | Open Access

    The improved genome assemblies of allotetraploid cotton species Gossypium hirsutum and Gossypium barbadense provide insights into cotton evolution and inform the construction of introgression lines used to identify loci associated with fiber quality.

    • Maojun Wang
    • , Lili Tu
    • , Daojun Yuan
    • , De Zhu
    • , Chao Shen
    • , Jianying Li
    • , Fuyan Liu
    • , Liuling Pei
    • , Pengcheng Wang
    • , Guannan Zhao
    • , Zhengxiu Ye
    • , Hui Huang
    • , Feilin Yan
    • , Yizan Ma
    • , Lin Zhang
    • , Min Liu
    • , Jiaqi You
    • , Yicheng Yang
    • , Zhenping Liu
    • , Fan Huang
    • , Baoqi Li
    • , Ping Qiu
    • , Qinghua Zhang
    • , Longfu Zhu
    • , Shuangxia Jin
    • , Xiyan Yang
    • , Ling Min
    • , Guoliang Li
    • , Ling-Ling Chen
    • , Hongkun Zheng
    • , Keith Lindsey
    • , Zhongxu Lin
    • , Joshua A. Udall
    •  & Xianlong Zhang
  • Letter |

    Individuals with biscuspid aortic valve and ascending aortic aneurysm show enrichment of rare variants in ROBO4. Functional studies suggest that ROBO4 mutations disrupt endothelial cell performance and contribute to pathological remodeling of aortic tissues.

    • Russell A. Gould
    • , Hamza Aziz
    • , Courtney E. Woods
    • , Manuel Alejandro Seman-Senderos
    • , Elizabeth Sparks
    • , Christoph Preuss
    • , Florian Wünnemann
    • , Djahida Bedja
    • , Cassandra R. Moats
    • , Sarah A. McClymont
    • , Rebecca Rose
    • , Nara Sobreira
    • , Hua Ling
    • , Gretchen MacCarrick
    • , Ajay Anand Kumar
    • , Ilse Luyckx
    • , Elyssa Cannaerts
    • , Aline Verstraeten
    • , Hanna M. Björk
    • , Ann-Cathrin Lehsau
    • , Vinod Jaskula-Ranga
    • , Henrik Lauridsen
    • , Asad A. Shah
    • , Christopher L. Bennett
    • , Patrick T. Ellinor
    • , Honghuang Lin
    • , Eric M. Isselbacher
    • , Christian Lacks Lino Cardenas
    • , Jonathan T. Butcher
    • , G. Chad Hughes
    • , Mark E. Lindsay
    • , David Valle
    • , Hua Ling
    • , James Lupski
    • , Harry C. Dietz
    • , Andrew S. McCallion
    • , Gregor Andelfinger
    • , Bart L. Loeys
    • , Lut Van Laer
    • , Per Eriksson
    • , Salah A. Mohamed
    • , Luc Mertens
    • , Anders Franco-Cereceda
    • , Seema Mital
    • , Luc Mertens
    • , Anders Franco-Cereceda
    • , Judith M. A. Verhagen
    • , Marja Wessels
    • , Salah A. Mohamed
    • , Per Eriksson
    • , Seema Mital
    • , Lut Van Laer
    • , Bart L. Loeys
    • , Gregor Andelfinger
    • , Andrew S. McCallion
    •  & Harry C. Dietz
  • Letter
    | Open Access

    Assembly of a pan-genome from 910 humans of African descent identifies 296.5 Mb of novel DNA mapping to 125,715 distinct contigs. This African pan-genome contains ~10% more DNA than the current human reference genome.

    • Rachel M. Sherman
    • , Juliet Forman
    • , Valentin Antonescu
    • , Daniela Puiu
    • , Michelle Daya
    • , Nicholas Rafaels
    • , Meher Preethi Boorgula
    • , Sameer Chavan
    • , Candelaria Vergara
    • , Victor E. Ortega
    • , Albert M. Levin
    • , Celeste Eng
    • , Maria Yazdanbakhsh
    • , James G. Wilson
    • , Javier Marrugo
    • , Leslie A. Lange
    • , L. Keoki Williams
    • , Harold Watson
    • , Lorraine B. Ware
    • , Christopher O. Olopade
    • , Olufunmilayo Olopade
    • , Ricardo R. Oliveira
    • , Carole Ober
    • , Dan L. Nicolae
    • , Deborah A. Meyers
    • , Alvaro Mayorga
    • , Jennifer Knight-Madden
    • , Tina Hartert
    • , Nadia N. Hansel
    • , Marilyn G. Foreman
    • , Jean G. Ford
    • , Mezbah U. Faruque
    • , Georgia M. Dunston
    • , Luis Caraballo
    • , Esteban G. Burchard
    • , Eugene R. Bleecker
    • , Maria I. Araujo
    • , Edwin F. Herrera-Paz
    • , Monica Campbell
    • , Cassandra Foster
    • , Margaret A. Taub
    • , Terri H. Beaty
    • , Ingo Ruczinski
    • , Rasika A. Mathias
    • , Kathleen C. Barnes
    •  & Steven L. Salzberg