Volume 50 Issue 4, April 2018

Volume 50 Issue 4

African Origins I. Shellfish-cognition-adornment.

Image: Art by Ree Treweek. Cover Design: Erin Dewalt.

Editorial

  • Editorial |

    Largely owing to inequitable distribution of resources, the United States is failing its population in healthcare, for which it vastly overspends relative to other wealthy countries. We advocate extending research in genetic epidemiology to oversample poor people, underserved ancestry groups and ethnic minorities, as well as to use genetic predisposition as a baseline from which to examine environmental influences on the costly comorbidities of common diseases.

    • Myles Axton

Correspondence

  • Correspondence |

    • Nicole A. Vasilevsky
    • , Erin D. Foster
    • , Mark E. Engelstad
    • , Leigh Carmody
    • , Matt Might
    • , Chip Chambers
    • , Hugh J. S. Dawkins
    • , Janine Lewis
    • , Maria G. Della Rocca
    • , Michelle Snyder
    • , Cornelius F. Boerkoel
    • , Ana Rath
    • , Sharon F. Terry
    • , Alastair Kent
    • , Beverly Searle
    • , Gareth Baynam
    • , Erik Jones
    • , Pam Gavin
    • , Michael Bamshad
    • , Jessica Chong
    • , Tudor Groza
    • , David Adams
    • , Adam C. Resnick
    • , Allison P. Heath
    • , Chris Mungall
    • , Ingrid A. Holm
    • , Kayli Rageth
    • , Catherine A. Brownstein
    • , Kent Shefchek
    • , Julie A. McMurry
    • , Peter N. Robinson
    • , Sebastian Köhler
    •  & Melissa A. Haendel

News & Views

  • News & Views |

    Noncoding expanded repeats have been implicated in a wide range of diseases. A new report uncovers expanded TTTCA and TTTTA repeats in an intronic region of SAMD12, and at least two other genes, in individuals with benign adult familial myoclonic epilepsy.

    • Marka van Blitterswijk
    •  & Rosa Rademakers
  • News & Views |

    The switch from fetal to adult hemoglobin relies on repression or silencing of the upstream γ-globin gene, but identification of the transcriptional repressors that bind to the sites at which a cluster of naturally occurring variants associated with HPFH (hereditary persistence of fetal hemoglobin) are found has been elusive. A new study provides mechanistic evidence for the direct binding of BCL11A and ZBTB7A, two previously identified γ-globin gene repressors.

    • Xunde Wang
    •  & Swee Lay Thein
  • News & Views |

    In vivo verification of tumor suppressors and their interactions with each other has required complex experiments. A report in this issue uses a novel CRISPR–Cas9 technology with barcodes to test, in parallel, the tumorigenic potential of functional loss of multiple tumor-suppressor genes in the context of a genetically engineered mouse model of lung adenocarcinoma with mutant Kras.

    • James Kim
    •  & John D. Minna

Brief Communications

  • Brief Communication |

    In vivo analysis of pairwise combinations of tumor suppressor losses using a barcode-based assay in mice identifies unpredicted genetic interactions and shows that the effects of tumor suppressor alterations can be context-dependent.

    • Zoë N. Rogers
    • , Christopher D. McFarland
    • , Ian P. Winters
    • , Jose A. Seoane
    • , Jennifer J. Brady
    • , Stephanie Yoon
    • , Christina Curtis
    • , Dmitri A. Petrov
    •  & Monte M. Winslow

Letters

  • Letter |

    Analysis of whole-genome sequencing data from 1,291 parent–offspring trios identifies patterns of clustered de novo mutations. Clusters increase in number with maternal age and are associated with DNA double-strand-break processes.

    • Jakob M. Goldmann
    • , Vladimir B. Seplyarskiy
    • , Wendy S. W. Wong
    • , Thierry Vilboux
    • , Pieter B. Neerincx
    • , Dale L. Bodian
    • , Benjamin D. Solomon
    • , Joris A. Veltman
    • , John F. Deeken
    • , Christian Gilissen
    •  & John E. Niederhuber
  • Letter |

    Single-cell RNA sequencing (scRNA-seq) of ~25,000 peripheral blood mononuclear cells from 45 donors identifies new celltype-specific cis-eQTLs and genetic variants that significantly alter co-expression relationships (‘co-expression QTLs’).

    • Monique G. P. van der Wijst
    • , Harm Brugge
    • , Dylan H. de Vries
    • , Patrick Deelen
    • , Morris A. Swertz
    •  & Lude Franke
  • Letter |

    The fetal globin gene repressors BCL11A and ZBTB7A directly bind γ-globin gene promoter regions. Repressor binding is disrupted by naturally occurring point mutations located upstream of the transcriptional start site that are associated with hereditary persistence of fetal hemoglobin.

    • Gabriella E. Martyn
    • , Beeke Wienert
    • , Lu Yang
    • , Manan Shah
    • , Laura J. Norton
    • , Jon Burdach
    • , Ryo Kurita
    • , Yukio Nakamura
    • , Richard C. M. Pearson
    • , Alister P. W. Funnell
    • , Kate G. R. Quinlan
    •  & Merlin Crossley
  • Letter |

    The authors study the cis-regulatory evolution of the Shh locus in vertebrates. Using genomic editing and chromatin profiling, they conclude that paired fins emerged through the co-option of developmental programs for the median fins of gnathostomes.

    • Joaquín Letelier
    • , Elisa de la Calle-Mustienes
    • , Joyce Pieretti
    • , Silvia Naranjo
    • , Ignacio Maeso
    • , Tetsuya Nakamura
    • , Juan Pascual-Anaya
    • , Neil H. Shubin
    • , Igor Schneider
    • , Juan Ramón Martinez-Morales
    •  & José Luis Gómez-Skarmeta
  • Letter |

    The authors present a CRISPR-library-based approach for highly efficient and precise genome-wide variant engineering. They examine the functional consequences of premature termination codons within all annotated essential genes in yeast.

    • Meru J. Sadhu
    • , Joshua S. Bloom
    • , Laura Day
    • , Jake J. Siegel
    • , Sriram Kosuri
    •  & Leonid Kruglyak

    Collection:

Articles

  • Article |

    This study investigates the effects of MYCN on the chromatin and transcriptional landscape of neuroblastoma. The authors find that, at oncogenic levels, MYCN binds to canonical E-boxes at promoters and invades enhancers, leading to transcriptional amplification.

    • Rhamy Zeid
    • , Matthew A. Lawlor
    • , Evon Poon
    • , Jaime M. Reyes
    • , Mariateresa Fulciniti
    • , Michael A. Lopez
    • , Thomas G. Scott
    • , Behnam Nabet
    • , Michael A. Erb
    • , Georg E. Winter
    • , Zoe Jacobson
    • , Donald R. Polaski
    • , Kristen L. Karlin
    • , Rachel A. Hirsch
    • , Nikhil P. Munshi
    • , Thomas F. Westbrook
    • , Louis Chesler
    • , Charles Y. Lin
    •  & James E. Bradner
  • Article |

    Multiancestry genome-wide association analyses identify new risk loci for stroke and stroke subtypes. Fine mapping and bioinformatics analyses of these risk loci point to mechanisms not previously implicated in stroke pathophysiology.

    • Rainer Malik
    • , Ganesh Chauhan
    • , Matthew Traylor
    • , Muralidharan Sargurupremraj
    • , Yukinori Okada
    • , Aniket Mishra
    • , Loes Rutten-Jacobs
    • , Anne-Katrin Giese
    • , Sander W. van der Laan
    • , Solveig Gretarsdottir
    • , Christopher D. Anderson
    • , Michael Chong
    • , Hieab H. H. Adams
    • , Tetsuro Ago
    • , Peter Almgren
    • , Philippe Amouyel
    • , Hakan Ay
    • , Traci M. Bartz
    • , Oscar R. Benavente
    • , Steve Bevan
    • , Giorgio B. Boncoraglio
    • , Robert D. Brown Jr
    • , Adam S. Butterworth
    • , Caty Carrera
    • , Cara L. Carty
    • , Daniel I. Chasman
    • , Wei-Min Chen
    • , John W. Cole
    • , Adolfo Correa
    • , Ioana Cotlarciuc
    • , Carlos Cruchaga
    • , John Danesh
    • , Paul I. W. de Bakker
    • , Anita L. DeStefano
    • , Marcel den Hoed
    • , Qing Duan
    • , Stefan T. Engelter
    • , Guido J. Falcone
    • , Rebecca F. Gottesman
    • , Raji P. Grewal
    • , Vilmundur Gudnason
    • , Stefan Gustafsson
    • , Jeffrey Haessler
    • , Tamara B. Harris
    • , Ahamad Hassan
    • , Aki S. Havulinna
    • , Susan R. Heckbert
    • , Elizabeth G. Holliday
    • , George Howard
    • , Fang-Chi Hsu
    • , Hyacinth I. Hyacinth
    • , M. Arfan Ikram
    • , Erik Ingelsson
    • , Marguerite R. Irvin
    • , Xueqiu Jian
    • , Jordi Jiménez-Conde
    • , Julie A. Johnson
    • , J. Wouter Jukema
    • , Masahiro Kanai
    • , Keith L. Keene
    • , Brett M. Kissela
    • , Dawn O. Kleindorfer
    • , Charles Kooperberg
    • , Michiaki Kubo
    • , Leslie A. Lange
    • , Carl D. Langefeld
    • , Claudia Langenberg
    • , Lenore J. Launer
    • , Jin-Moo Lee
    • , Robin Lemmens
    • , Didier Leys
    • , Cathryn M. Lewis
    • , Wei-Yu Lin
    • , Arne G. Lindgren
    • , Erik Lorentzen
    • , Patrik K. Magnusson
    • , Jane Maguire
    • , Ani Manichaikul
    • , Patrick F. McArdle
    • , James F. Meschia
    • , Braxton D. Mitchell
    • , Thomas H. Mosley
    • , Michael A. Nalls
    • , Toshiharu Ninomiya
    • , Martin J. O’Donnell
    • , Bruce M. Psaty
    • , Sara L. Pulit
    • , Kristiina Rannikmäe
    • , Alexander P. Reiner
    • , Kathryn M. Rexrode
    • , Kenneth Rice
    • , Stephen S. Rich
    • , Paul M. Ridker
    • , Natalia S. Rost
    • , Peter M. Rothwell
    • , Jerome I. Rotter
    • , Tatjana Rundek
    • , Ralph L. Sacco
    • , Saori Sakaue
    • , Michele M. Sale
    • , Veikko Salomaa
    • , Bishwa R. Sapkota
    • , Reinhold Schmidt
    • , Carsten O. Schmidt
    • , Ulf Schminke
    • , Pankaj Sharma
    • , Agnieszka Slowik
    • , Cathie L. M. Sudlow
    • , Christian Tanislav
    • , Turgut Tatlisumak
    • , Kent D. Taylor
    • , Vincent N. S. Thijs
    • , Gudmar Thorleifsson
    • , Unnur Thorsteinsdottir
    • , Steffen Tiedt
    • , Stella Trompet
    • , Christophe Tzourio
    • , Cornelia M. van Duijn
    • , Matthew Walters
    • , Nicholas J. Wareham
    • , Sylvia Wassertheil-Smoller
    • , James G. Wilson
    • , Kerri L. Wiggins
    • , Qiong Yang
    • , Salim Yusuf
    • , Joshua C. Bis
    • , Tomi Pastinen
    • , Arno Ruusalepp
    • , Eric E. Schadt
    • , Simon Koplev
    • , Johan L. M. Björkegren
    • , Veronica Codoni
    • , Mete Civelek
    • , Nicholas L. Smith
    • , David A. Trégouët
    • , Ingrid E. Christophersen
    • , Carolina Roselli
    • , Steven A. Lubitz
    • , Patrick T. Ellinor
    • , E. Shyong Tai
    • , Jaspal S. Kooner
    • , Norihiro Kato
    • , Jiang He
    • , Pim van der Harst
    • , Paul Elliott
    • , John C. Chambers
    • , Fumihiko Takeuchi
    • , Andrew D. Johnson
    • , Rainer Malik
    • , Ganesh Chauhan
    • , Matthew Traylor
    • , Muralidharan Sargurupremraj
    • , Yukinori Okada
    • , Aniket Mishra
    • , Loes Rutten-Jacobs
    • , Anne-Katrin Giese
    • , Sander W. van der Laan
    • , Solveig Gretarsdottir
    • , Christopher D. Anderson
    • , Michael Chong
    • , Hieab H. H. Adams
    • , Tetsuro Ago
    • , Peter Almgren
    • , Philippe Amouyel
    • , Hakan Ay
    • , Traci M. Bartz
    • , Oscar R. Benavente
    • , Steve Bevan
    • , Giorgio B. Boncoraglio
    • , Robert D. Brown Jr
    • , Adam S. Butterworth
    • , Caty Carrera
    • , Cara L. Carty
    • , Daniel I. Chasman
    • , Wei-Min Chen
    • , John W. Cole
    • , Adolfo Correa
    • , Ioana Cotlarciuc
    • , Carlos Cruchaga
    • , John Danesh
    • , Paul I. W. de Bakker
    • , Anita L. DeStefano
    • , Marcel den Hoed
    • , Qing Duan
    • , Stefan T. Engelter
    • , Guido J. Falcone
    • , Rebecca F. Gottesman
    • , Raji P. Grewal
    • , Vilmundur Gudnason
    • , Stefan Gustafsson
    • , Jeffrey Haessler
    • , Tamara B. Harris
    • , Ahamad Hassan
    • , Aki S. Havulinna
    • , Susan R. Heckbert
    • , Elizabeth G. Holliday
    • , George Howard
    • , Fang-Chi Hsu
    • , Hyacinth I. Hyacinth
    • , M. Arfan Ikram
    • , Erik Ingelsson
    • , Marguerite R. Irvin
    • , Xueqiu Jian
    • , Jordi Jiménez-Conde
    • , Julie A. Johnson
    • , J. Wouter Jukema
    • , Masahiro Kanai
    • , Keith L. Keene
    • , Brett M. Kissela
    • , Dawn O. Kleindorfer
    • , Charles Kooperberg
    • , Michiaki Kubo
    • , Leslie A. Lange
    • , Carl D. Langefeld
    • , Claudia Langenberg
    • , Lenore J. Launer
    • , Jin-Moo Lee
    • , Robin Lemmens
    • , Didier Leys
    • , Cathryn M. Lewis
    • , Wei-Yu Lin
    • , Arne G. Lindgren
    • , Erik Lorentzen
    • , Patrik K. Magnusson
    • , Jane Maguire
    • , Ani Manichaikul
    • , Patrick F. McArdle
    • , James F. Meschia
    • , Braxton D. Mitchell
    • , Thomas H. Mosley
    • , Michael A. Nalls
    • , Toshiharu Ninomiya
    • , Martin J. O’Donnell
    • , Bruce M. Psaty
    • , Sara L. Pulit
    • , Kristiina Rannikmäe
    • , Alexander P. Reiner
    • , Kathryn M. Rexrode
    • , Kenneth Rice
    • , Stephen S. Rich
    • , Paul M. Ridker
    • , Natalia S. Rost
    • , Peter M. Rothwell
    • , Jerome I. Rotter
    • , Tatjana Rundek
    • , Ralph L. Sacco
    • , Saori Sakaue
    • , Michele M. Sale
    • , Veikko Salomaa
    • , Bishwa R. Sapkota
    • , Reinhold Schmidt
    • , Carsten O. Schmidt
    • , Ulf Schminke
    • , Pankaj Sharma
    • , Agnieszka Slowik
    • , Cathie L. M. Sudlow
    • , Christian Tanislav
    • , Turgut Tatlisumak
    • , Kent D. Taylor
    • , Vincent N. S. Thijs
    • , Gudmar Thorleifsson
    • , Unnur Thorsteinsdottir
    • , Steffen Tiedt
    • , Stella Trompet
    • , Christophe Tzourio
    • , Cornelia M. van Duijn
    • , Matthew Walters
    • , Nicholas J. Wareham
    • , Sylvia Wassertheil-Smoller
    • , James G. Wilson
    • , Kerri L. Wiggins
    • , Qiong Yang
    • , Salim Yusuf
    • , Najaf Amin
    • , Hugo S. Aparicio
    • , Donna K. Arnett
    • , John Attia
    • , Alexa S. Beiser
    • , Claudine Berr
    • , Julie E. Buring
    • , Mariana Bustamante
    • , Valeria Caso
    • , Yu-Ching Cheng
    • , Seung Hoan Choi
    • , Ayesha Chowhan
    • , Natalia Cullell
    • , Jean-François Dartigues
    • , Hossein Delavaran
    • , Pilar Delgado
    • , Marcus Dörr
    • , Gunnar Engström
    • , Ian Ford
    • , Wander S. Gurpreet
    • , Anders Hamsten
    • , Laura Heitsch
    • , Atsushi Hozawa
    • , Laura Ibanez
    • , Andreea Ilinca
    • , Martin Ingelsson
    • , Motoki Iwasaki
    • , Rebecca D. Jackson
    • , Katarina Jood
    • , Pekka Jousilahti
    • , Sara Kaffashian
    • , Lalit Kalra
    • , Masahiro Kamouchi
    • , Takanari Kitazono
    • , Olafur Kjartansson
    • , Manja Kloss
    • , Peter J. Koudstaal
    • , Jerzy Krupinski
    • , Daniel L. Labovitz
    • , Cathy C. Laurie
    • , Christopher R. Levi
    • , Linxin Li
    • , Lars Lind
    • , Cecilia M. Lindgren
    • , Vasileios Lioutas
    • , Yong Mei Liu
    • , Oscar L. Lopez
    • , Hirata Makoto
    • , Nicolas Martinez-Majander
    • , Koichi Matsuda
    • , Naoko Minegishi
    • , Joan Montaner
    • , Andrew P. Morris
    • , Elena Muiño
    • , Martina Müller-Nurasyid
    • , Bo Norrving
    • , Soichi Ogishima
    • , Eugenio A. Parati
    • , Leema Reddy Peddareddygari
    • , Nancy L. Pedersen
    • , Joanna Pera
    • , Markus Perola
    • , Alessandro Pezzini
    • , Silvana Pileggi
    • , Raquel Rabionet
    • , Iolanda Riba-Llena
    • , Marta Ribasés
    • , Jose R. Romero
    • , Jaume Roquer
    • , Anthony G. Rudd
    • , Antti-Pekka Sarin
    • , Ralhan Sarju
    • , Chloe Sarnowski
    • , Makoto Sasaki
    • , Claudia L. Satizabal
    • , Mamoru Satoh
    • , Naveed Sattar
    • , Norie Sawada
    • , Gerli Sibolt
    • , Ásgeir Sigurdsson
    • , Albert Smith
    • , Kenji Sobue
    • , Carolina Soriano-Tárraga
    • , Tara Stanne
    • , O. Colin Stine
    • , David J. Stott
    • , Konstantin Strauch
    • , Takako Takai
    • , Hideo Tanaka
    • , Kozo Tanno
    • , Alexander Teumer
    • , Liisa Tomppo
    • , Nuria P. Torres-Aguila
    • , Emmanuel Touze
    • , Shoichiro Tsugane
    • , Andre G. Uitterlinden
    • , Einar M. Valdimarsson
    • , Sven J. van der Lee
    • , Henry Völzke
    • , Kenji Wakai
    • , David Weir
    • , Stephen R. Williams
    • , Charles D. A. Wolfe
    • , Quenna Wong
    • , Huichun Xu
    • , Taiki Yamaji
    • , Dharambir K. Sanghera
    • , Olle Melander
    • , Christina Jern
    • , Daniel Strbian
    • , Israel Fernandez-Cadenas
    • , W. T. Longstreth Jr
    • , Arndt Rolfs
    • , Jun Hata
    • , Daniel Woo
    • , Jonathan Rosand
    • , Guillaume Pare
    • , Jemma C. Hopewell
    • , Danish Saleheen
    • , Kari Stefansson
    • , Bradford B. Worrall
    • , Steven J. Kittner
    • , Sudha Seshadri
    • , Myriam Fornage
    • , Hugh S. Markus
    • , Joanna M. M. Howson
    • , Yoichiro Kamatani
    • , Stephanie Debette
    • , Martin Dichgans
    • , Dharambir K. Sanghera
    • , Olle Melander
    • , Christina Jern
    • , Daniel Strbian
    • , Israel Fernandez-Cadenas
    • , W. T. Longstreth Jr
    • , Arndt Rolfs
    • , Jun Hata
    • , Daniel Woo
    • , Jonathan Rosand
    • , Guillaume Pare
    • , Jemma C. Hopewell
    • , Danish Saleheen
    • , Kari Stefansson
    • , Bradford B. Worrall
    • , Steven J. Kittner
    • , Sudha Seshadri
    • , Myriam Fornage
    • , Hugh S. Markus
    • , Joanna M. M. Howson
    • , Yoichiro Kamatani
    • , Stephanie Debette
    •  & Martin Dichgans
  • Article |

    A transcriptome-wide association study integrating genome-wide association data with expression data from brain, blood and adipose tissues identifies new candidate susceptibility genes for schizophrenia, providing a step toward understanding the underlying biology.

    • Alexander Gusev
    • , Nicholas Mancuso
    • , Hyejung Won
    • , Maria Kousi
    • , Hilary K. Finucane
    • , Yakir Reshef
    • , Lingyun Song
    • , Alexias Safi
    • , Steven McCarroll
    • , Benjamin M. Neale
    • , Roel A. Ophoff
    • , Michael C. O’Donovan
    • , Gregory E. Crawford
    • , Daniel H. Geschwind
    • , Nicholas Katsanis
    • , Patrick F. Sullivan
    • , Bogdan Pasaniuc
    •  & Alkes L. Price
  • Article |

    Genome-wide association study for osteoarthritis using data from UK Biobank identifies loci for knee- and hip-specific disease. Functional analyses of chondrocytes provide further insight into candidate causal genes.

    • Eleni Zengini
    • , Konstantinos Hatzikotoulas
    • , Ioanna Tachmazidou
    • , Julia Steinberg
    • , Fernando P. Hartwig
    • , Lorraine Southam
    • , Sophie Hackinger
    • , Cindy G. Boer
    • , Unnur Styrkarsdottir
    • , Arthur Gilly
    • , Daniel Suveges
    • , Britt Killian
    • , Thorvaldur Ingvarsson
    • , Helgi Jonsson
    • , George C. Babis
    • , Andrew McCaskie
    • , Andre G. Uitterlinden
    • , Joyce B. J. van Meurs
    • , Unnur Thorsteinsdottir
    • , Kari Stefansson
    • , George Davey Smith
    • , Jeremy M. Wilkinson
    •  & Eleftheria Zeggini

    Collection:

  • Article |

    Trans-ethnic analyses of exome array data identify new risk loci for type 2 diabetes. Fine-mapping analyses using genome-wide association data show that the index coding variants represent the likely causal variants at only a subset of these loci.

    • Anubha Mahajan
    • , Jennifer Wessel
    • , Sara M. Willems
    • , Wei Zhao
    • , Neil R. Robertson
    • , Audrey Y. Chu
    • , Wei Gan
    • , Hidetoshi Kitajima
    • , Daniel Taliun
    • , N. William Rayner
    • , Xiuqing Guo
    • , Yingchang Lu
    • , Man Li
    • , Richard A. Jensen
    • , Yao Hu
    • , Shaofeng Huo
    • , Kurt K. Lohman
    • , Weihua Zhang
    • , James P. Cook
    • , Bram Peter Prins
    • , Jason Flannick
    • , Niels Grarup
    • , Vassily Vladimirovich Trubetskoy
    • , Jasmina Kravic
    • , Young Jin Kim
    • , Denis V. Rybin
    • , Hanieh Yaghootkar
    • , Martina Müller-Nurasyid
    • , Karina Meidtner
    • , Ruifang Li-Gao
    • , Tibor V. Varga
    • , Jonathan Marten
    • , Jin Li
    • , Albert Vernon Smith
    • , Ping An
    • , Symen Ligthart
    • , Stefan Gustafsson
    • , Giovanni Malerba
    • , Ayse Demirkan
    • , Juan Fernandez Tajes
    • , Valgerdur Steinthorsdottir
    • , Matthias Wuttke
    • , Cécile Lecoeur
    • , Michael Preuss
    • , Lawrence F. Bielak
    • , Marielisa Graff
    • , Heather M. Highland
    • , Anne E. Justice
    • , Dajiang J. Liu
    • , Eirini Marouli
    • , Gina Marie Peloso
    • , Helen R. Warren
    • , Saima Afaq
    • , Shoaib Afzal
    • , Emma Ahlqvist
    • , Peter Almgren
    • , Najaf Amin
    • , Lia B. Bang
    • , Alain G. Bertoni
    • , Cristina Bombieri
    • , Jette Bork-Jensen
    • , Ivan Brandslund
    • , Jennifer A. Brody
    • , Noël P. Burtt
    • , Mickaël Canouil
    • , Yii-Der Ida Chen
    • , Yoon Shin Cho
    • , Cramer Christensen
    • , Sophie V. Eastwood
    • , Kai-Uwe Eckardt
    • , Krista Fischer
    • , Giovanni Gambaro
    • , Vilmantas Giedraitis
    • , Megan L. Grove
    • , Hugoline G. de Haan
    • , Sophie Hackinger
    • , Yang Hai
    • , Sohee Han
    • , Anne Tybjærg-Hansen
    • , Marie-France Hivert
    • , Bo Isomaa
    • , Susanne Jäger
    • , Marit E. Jørgensen
    • , Torben Jørgensen
    • , Annemari Käräjämäki
    • , Bong-Jo Kim
    • , Sung Soo Kim
    • , Heikki A. Koistinen
    • , Peter Kovacs
    • , Jennifer Kriebel
    • , Florian Kronenberg
    • , Kristi Läll
    • , Leslie A. Lange
    • , Jung-Jin Lee
    • , Benjamin Lehne
    • , Huaixing Li
    • , Keng-Hung Lin
    • , Allan Linneberg
    • , Ching-Ti Liu
    • , Jun Liu
    • , Marie Loh
    • , Reedik Mägi
    • , Vasiliki Mamakou
    • , Roberta McKean-Cowdin
    • , Girish Nadkarni
    • , Matt Neville
    • , Sune F. Nielsen
    • , Ioanna Ntalla
    • , Patricia A. Peyser
    • , Wolfgang Rathmann
    • , Kenneth Rice
    • , Stephen S. Rich
    • , Line Rode
    • , Olov Rolandsson
    • , Sebastian Schönherr
    • , Elizabeth Selvin
    • , Kerrin S. Small
    • , Alena Stančáková
    • , Praveen Surendran
    • , Kent D. Taylor
    • , Tanya M. Teslovich
    • , Barbara Thorand
    • , Gudmar Thorleifsson
    • , Adrienne Tin
    • , Anke Tönjes
    • , Anette Varbo
    • , Daniel R. Witte
    • , Andrew R. Wood
    • , Pranav Yajnik
    • , Jie Yao
    • , Loïc Yengo
    • , Robin Young
    • , Philippe Amouyel
    • , Heiner Boeing
    • , Eric Boerwinkle
    • , Erwin P. Bottinger
    • , Rajiv Chowdhury
    • , Francis S. Collins
    • , George Dedoussis
    • , Abbas Dehghan
    • , Panos Deloukas
    • , Marco M. Ferrario
    • , Jean Ferrières
    • , Jose C. Florez
    • , Philippe Frossard
    • , Vilmundur Gudnason
    • , Tamara B. Harris
    • , Susan R. Heckbert
    • , Joanna M. M. Howson
    • , Martin Ingelsson
    • , Sekar Kathiresan
    • , Frank Kee
    • , Johanna Kuusisto
    • , Claudia Langenberg
    • , Lenore J. Launer
    • , Cecilia M. Lindgren
    • , Satu Männistö
    • , Thomas Meitinger
    • , Olle Melander
    • , Karen L. Mohlke
    • , Marie Moitry
    • , Andrew D. Morris
    • , Alison D. Murray
    • , Renée de Mutsert
    • , Marju Orho-Melander
    • , Katharine R. Owen
    • , Markus Perola
    • , Annette Peters
    • , Michael A. Province
    • , Asif Rasheed
    • , Paul M. Ridker
    • , Fernando Rivadineira
    • , Frits R. Rosendaal
    • , Anders H. Rosengren
    • , Veikko Salomaa
    • , Wayne H.-H. Sheu
    • , Rob Sladek
    • , Blair H. Smith
    • , Konstantin Strauch
    • , André G. Uitterlinden
    • , Rohit Varma
    • , Cristen J. Willer
    • , Matthias Blüher
    • , Adam S. Butterworth
    • , John Campbell Chambers
    • , Daniel I. Chasman
    • , John Danesh
    • , Cornelia van Duijn
    • , Josée Dupuis
    • , Oscar H. Franco
    • , Paul W. Franks
    • , Philippe Froguel
    • , Harald Grallert
    • , Leif Groop
    • , Bok-Ghee Han
    • , Torben Hansen
    • , Andrew T. Hattersley
    • , Caroline Hayward
    • , Erik Ingelsson
    • , Sharon L. R. Kardia
    • , Fredrik Karpe
    • , Jaspal Singh Kooner
    • , Anna Köttgen
    • , Kari Kuulasmaa
    • , Markku Laakso
    • , Xu Lin
    • , Lars Lind
    • , Yongmei Liu
    • , Ruth J. F. Loos
    • , Jonathan Marchini
    • , Andres Metspalu
    • , Dennis Mook-Kanamori
    • , Børge G. Nordestgaard
    • , Colin N. A. Palmer
    • , James S. Pankow
    • , Oluf Pedersen
    • , Bruce M. Psaty
    • , Rainer Rauramaa
    • , Naveed Sattar
    • , Matthias B. Schulze
    • , Nicole Soranzo
    • , Timothy D. Spector
    • , Kari Stefansson
    • , Michael Stumvoll
    • , Unnur Thorsteinsdottir
    • , Tiinamaija Tuomi
    • , Jaakko Tuomilehto
    • , Nicholas J. Wareham
    • , James G. Wilson
    • , Eleftheria Zeggini
    • , Robert A. Scott
    • , Inês Barroso
    • , Timothy M. Frayling
    • , Mark O. Goodarzi
    • , James B. Meigs
    • , Michael Boehnke
    • , Danish Saleheen
    • , Andrew P. Morris
    • , Jerome I. Rotter
    •  & Mark I. McCarthy
  • Article |

    Analysis of the imprinted KLF14 locus shows that the type 2 diabetes risk alleles in this region act in adipocytes to reduce KLF14 expression and modulate the expression of almost 400 genes in trans, leading to a shift in body-fat distribution and insulin resistance specifically in females.

    • Kerrin S. Small
    • , Marijana Todorčević
    • , Mete Civelek
    • , Julia S. El-Sayed Moustafa
    • , Xiao Wang
    • , Michelle M. Simon
    • , Juan Fernandez-Tajes
    • , Anubha Mahajan
    • , Momoko Horikoshi
    • , Alison Hugill
    • , Craig A. Glastonbury
    • , Lydia Quaye
    • , Matt J. Neville
    • , Siddharth Sethi
    • , Marianne Yon
    • , Calvin Pan
    • , Nam Che
    • , Ana Viñuela
    • , Pei-Chien Tsai
    • , Abhishek Nag
    • , Alfonso Buil
    • , Gudmar Thorleifsson
    • , Avanthi Raghavan
    • , Qiurong Ding
    • , Andrew P. Morris
    • , Jordana T. Bell
    • , Unnur Thorsteinsdottir
    • , Kari Stefansson
    • , Markku Laakso
    • , Ingrid Dahlman
    • , Peter Arner
    • , Anna L. Gloyn
    • , Kiran Musunuru
    • , Aldons J. Lusis
    • , Roger D. Cox
    • , Fredrik Karpe
    •  & Mark I. McCarthy
  • Article |

    This study identifies TTTCA- and TTTTA-repeat expansions in benign adult familial myoclonic epilepsy. Cortical neurons from affected people exhibit RNA foci containing these expanded repeats, suggesting RNA toxicity as the mechanism underlying disease pathogenesis.

    • Hiroyuki Ishiura
    • , Koichiro Doi
    • , Jun Mitsui
    • , Jun Yoshimura
    • , Miho Kawabe Matsukawa
    • , Asao Fujiyama
    • , Yasuko Toyoshima
    • , Akiyoshi Kakita
    • , Hitoshi Takahashi
    • , Yutaka Suzuki
    • , Sumio Sugano
    • , Wei Qu
    • , Kazuki Ichikawa
    • , Hideaki Yurino
    • , Koichiro Higasa
    • , Shota Shibata
    • , Aki Mitsue
    • , Masaki Tanaka
    • , Yaeko Ichikawa
    • , Yuji Takahashi
    • , Hidetoshi Date
    • , Takashi Matsukawa
    • , Junko Kanda
    • , Fumiko Kusunoki Nakamoto
    • , Mana Higashihara
    • , Koji Abe
    • , Ryoko Koike
    • , Mutsuo Sasagawa
    • , Yasuko Kuroha
    • , Naoya Hasegawa
    • , Norio Kanesawa
    • , Takayuki Kondo
    • , Takefumi Hitomi
    • , Masayoshi Tada
    • , Hiroki Takano
    • , Yutaka Saito
    • , Kazuhiro Sanpei
    • , Osamu Onodera
    • , Masatoyo Nishizawa
    • , Masayuki Nakamura
    • , Takeshi Yasuda
    • , Yoshio Sakiyama
    • , Mieko Otsuka
    • , Akira Ueki
    • , Ken-ichi Kaida
    • , Jun Shimizu
    • , Ritsuko Hanajima
    • , Toshihiro Hayashi
    • , Yasuo Terao
    • , Satomi Inomata-Terada
    • , Masashi Hamada
    • , Yuichiro Shirota
    • , Akatsuki Kubota
    • , Yoshikazu Ugawa
    • , Kishin Koh
    • , Yoshihisa Takiyama
    • , Natsumi Ohsawa-Yoshida
    • , Shoichi Ishiura
    • , Ryo Yamasaki
    • , Akira Tamaoka
    • , Hiroshi Akiyama
    • , Taisuke Otsuki
    • , Akira Sano
    • , Akio Ikeda
    • , Jun Goto
    • , Shinichi Morishita
    •  & Shoji Tsuji
  • Article |

    Whole-genome DNA methylation profiling and analysis of normal tissues from both human and mouse reveal that hypomethylation within partially methylated, late-replicating domains depends on sequence context, starts early in development, accumulates with cell divisions and progresses with organismal aging.

    • Wanding Zhou
    • , Huy Q. Dinh
    • , Zachary Ramjan
    • , Daniel J. Weisenberger
    • , Charles M. Nicolet
    • , Hui Shen
    • , Peter W. Laird
    •  & Benjamin P. Berman
  • Article |

    A genome-wide CRISPR screen for suppressors and enhancers of C9ORF72 dipeptide-repeat protein toxicity identifies candidate genes involved in nucleocytoplasmic transport and other pathways including RNA processing and chromatin modification.

    • Nicholas J. Kramer
    • , Michael S. Haney
    • , David W. Morgens
    • , Ana Jovičić
    • , Julien Couthouis
    • , Amy Li
    • , James Ousey
    • , Rosanna Ma
    • , Gregor Bieri
    • , C. Kimberly Tsui
    • , Yingxiao Shi
    • , Nicholas T. Hertz
    • , Marc Tessier-Lavigne
    • , Justin K. Ichida
    • , Michael C. Bassik
    •  & Aaron D. Gitler
  • Article |

    Analysis of whole-genome sequences and transcription data from tumors identifies noncoding loci in which mutations affect target gene expression. These somatic eQTLs can classify tumors into pathway-based subtypes and are disrupted in 88% of tumors.

    • Wei Zhang
    • , Ana Bojorquez-Gomez
    • , Daniel Ortiz Velez
    • , Guorong Xu
    • , Kyle S. Sanchez
    • , John Paul Shen
    • , Kevin Chen
    • , Katherine Licon
    • , Collin Melton
    • , Katrina M. Olson
    • , Michael Ku Yu
    • , Justin K. Huang
    • , Hannah Carter
    • , Emma K. Farley
    • , Michael Snyder
    • , Stephanie I. Fraley
    • , Jason F. Kreisberg
    •  & Trey Ideker

Analysis

  • Analysis |

    A new method tests whether disease heritability is enriched near genes with high tissue-specific expression. The authors use gene expression data together with GWAS summary statistics for 48 diseases and traits to identify disease-relevant tissues.

    • Hilary K. Finucane
    • , Yakir A. Reshef
    • , Verneri Anttila
    • , Kamil Slowikowski
    • , Alexander Gusev
    • , Andrea Byrnes
    • , Steven Gazal
    • , Po-Ru Loh
    • , Caleb Lareau
    • , Noam Shoresh
    • , Giulio Genovese
    • , Arpiar Saunders
    • , Evan Macosko
    • , Samuela Pollack
    • , John R. B. Perry
    • , Jason D. Buenrostro
    • , Bradley E. Bernstein
    • , Soumya Raychaudhuri
    • , Steven McCarroll
    • , Benjamin M. Neale
    •  & Alkes L. Price