Volume 49 Issue 1, January 2017

Volume 49 Issue 1

Cover image: barley inflorescence (pp 8 and 157)

Editorial

  • Editorial |

    Agriculture has depended since its Neolithic origins upon spontaneous or induced genetic variation. Human selection on naturally occurring variation in flowering is the most frequent source of domesticated crop plants. In the current era of rapid technological advance in reading and writing genomes, we advocate universal access to some safe modular variation in flower, leaf and color traits that can be operated without labs or restrictions by ordinary farmers and gardeners.

Correspondence

News and Views

  • News & Views |

    Our understanding of how DNA copy number changes contribute to disease, including cancer, has to a large degree been focused on the changes in gene dosage that they generate and has neglected the effects of the DNA rearrangements that lead to their formation. A new study reports an innovative analytical framework for copy number alterations that are oncogenic primarily owing to the genomic rearrangements that underlie them.

    • Rameen Beroukhim
    • , Xiaoyang Zhang
    •  & Matthew Meyerson
  • News & Views |

    A genome-wide study of fasting insulin, HDL cholesterol and triglycerides, designed to depict insulin resistance, identified 53 independent loci associated with a limited capacity to store fat in a healthy way. The increased power of this multitrait approach provides insights into an otherwise difficult-to-grasp phenotype.

    • Iris M Heid
    •  & Thomas W Winkler
  • News & Views |

    A defining characteristic of grasses, including major cereal crops, is the way in which flowers are arranged on an inflorescence. A new study finds that regulation of hormone levels during development is crucial for determining the arrangement of flowers on a barley inflorescence, opening new doors for increasing grain yield.

    • Scott A Boden

Analysis

  • Analysis |

    Andrew Lane and colleagues analyze somatic alterations across 21 tumor types for evidence of sex bias. They find that an excess of genes on the non-pseudoautosomal region of the X chromosome harbor loss-of-function mutations more frequently in males, suggesting that biallelic expression of these genes in females contributes to reduced cancer incidence in females across a variety of tumor types.

    • Andrew Dunford
    • , David M Weinstock
    • , Virginia Savova
    • , Steven E Schumacher
    • , John P Cleary
    • , Akinori Yoda
    • , Timothy J Sullivan
    • , Julian M Hess
    • , Alexander A Gimelbrant
    • , Rameen Beroukhim
    • , Michael S Lawrence
    • , Gad Getz
    •  & Andrew A Lane

Articles

  • Article |

    Luca Lotta, Robert Scott, Stephen O’Rahilly, Claudia Langenberg, David Savage, Nicholas Wareham, Inês Barroso and colleagues identify 53 genomic regions associated with insulin resistance phenotypes. Their findings suggest that limited storage capacity of peripheral adipose tissue is an important etiological component in insulin-resistant cardiometabolic disease and highlight genes and mechanisms underpinning this link.

    • Luca A Lotta
    • , Pawan Gulati
    • , Felix R Day
    • , Felicity Payne
    • , Halit Ongen
    • , Martijn van de Bunt
    • , Kyle J Gaulton
    • , John D Eicher
    • , Stephen J Sharp
    • , Jian'an Luan
    • , Emanuella De Lucia Rolfe
    • , Isobel D Stewart
    • , Eleanor Wheeler
    • , Sara M Willems
    • , Claire Adams
    • , Hanieh Yaghootkar
    • , EPIC-InterAct Consortium
    • , Claudia Langenberg
    • , Robert A Scott
    • , Stephen J Sharp
    • , Nita G Forouhi
    • , Nicola D Kerrison
    • , Matt Sims
    • , Debora M E Lucarelli
    • , Inês Barroso
    • , Panos Deloukas
    • , Mark I McCarthy
    • , Larraitz Arriola
    • , Beverley Balkau
    • , Aurelio Barricarte
    • , Heiner Boeing
    • , Paul W Franks
    • , Carlos Gonzalez
    • , Sara Grioni
    • , Rudolf Kaaks
    • , Timothy J Key
    • , Carmen Navarro
    • , Peter M Nilsson
    • , Kim Overvad
    • , Domenico Palli
    • , Salvatore Panico
    • , J Ramón Quirós
    • , Olov Rolandsson
    • , Carlotta Sacerdote
    • , Elena Salamanca-Fernández
    • , Nadia Slimani
    • , Anne Tjonneland
    • , Rosario Tumino
    • , Annemieke M W Spijkerman
    • , Daphne L van der A
    • , Yvonne T van der Schouw
    • , Elio Riboli
    • , Nicholas J Wareham
    • , Cambridge FPLD1 Consortium
    • , Robert K Semple
    • , Claire Adams
    • , Anna Stears
    • , Stella George
    • , Mark Walker
    • , Ellie Gurnell
    • , Deirdre Maguire
    • , Rasha Mukhtar
    • , Sath Nag
    • , Amanda Adler
    • , Maarten R Soeters
    • , Ken Laji
    • , Alistair Watt
    • , Simon Aylwin
    • , Andrew Johnson
    • , Gerry Rayman
    • , Fahmy Hanna
    • , Sian Ellard
    • , Richard Ross
    • , Kristina Blaslov
    • , Lea Smirčić Duvnjak
    • , Stephen O'Rahilly
    • , David B Savage
    • , Nita G Forouhi
    • , Kay-Tee Khaw
    • , Andrew D Johnson
    • , Robert K Semple
    • , Timothy Frayling
    • , John R B Perry
    • , Emmanouil Dermitzakis
    • , Mark I McCarthy
    • , Inês Barroso
    • , Nicholas J Wareham
    • , David B Savage
    • , Claudia Langenberg
    • , Stephen O'Rahilly
    •  & Robert A Scott
  • Article |

    The CNV analysis group of the Psychiatric Genomic Consortium analyzes a large schizophrenia cohort to examine genomic copy number variants (CNVs) and disease risk. They find an enrichment of CNV burden in cases versus controls and identify 8 genome-wide significant loci as well as novel suggestive loci conferring either risk or protection to schizophrenia.

    • Christian R Marshall
    • , Daniel P Howrigan
    • , Daniele Merico
    • , Bhooma Thiruvahindrapuram
    • , Wenting Wu
    • , Douglas S Greer
    • , Danny Antaki
    • , Aniket Shetty
    • , Peter A Holmans
    • , Dalila Pinto
    • , Madhusudan Gujral
    • , William M Brandler
    • , Dheeraj Malhotra
    • , Zhouzhi Wang
    • , Karin V Fuentes Fajarado
    • , Michelle S Maile
    • , Stephan Ripke
    • , Ingrid Agartz
    • , Margot Albus
    • , Madeline Alexander
    • , Farooq Amin
    • , Joshua Atkins
    • , Silviu A Bacanu
    • , Richard A Belliveau Jr
    • , Sarah E Bergen
    • , Marcelo Bertalan
    • , Elizabeth Bevilacqua
    • , Tim B Bigdeli
    • , Donald W Black
    • , Richard Bruggeman
    • , Nancy G Buccola
    • , Randy L Buckner
    • , Brendan Bulik-Sullivan
    • , William Byerley
    • , Wiepke Cahn
    • , Guiqing Cai
    • , Murray J Cairns
    • , Dominique Campion
    • , Rita M Cantor
    • , Vaughan J Carr
    • , Noa Carrera
    • , Stanley V Catts
    • , Kimberley D Chambert
    • , Wei Cheng
    • , C Robert Cloninger
    • , David Cohen
    • , Paul Cormican
    • , Nick Craddock
    • , Benedicto Crespo-Facorro
    • , James J Crowley
    • , David Curtis
    • , Michael Davidson
    • , Kenneth L Davis
    • , Franziska Degenhardt
    • , Jurgen Del Favero
    • , Lynn E DeLisi
    • , Dimitris Dikeos
    • , Timothy Dinan
    • , Srdjan Djurovic
    • , Gary Donohoe
    • , Elodie Drapeau
    • , Jubao Duan
    • , Frank Dudbridge
    • , Peter Eichhammer
    • , Johan Eriksson
    • , Valentina Escott-Price
    • , Laurent Essioux
    • , Ayman H Fanous
    • , Kai-How Farh
    • , Martilias S Farrell
    • , Josef Frank
    • , Lude Franke
    • , Robert Freedman
    • , Nelson B Freimer
    • , Joseph I Friedman
    • , Andreas J Forstner
    • , Menachem Fromer
    • , Giulio Genovese
    • , Lyudmila Georgieva
    • , Elliot S Gershon
    • , Ina Giegling
    • , Paola Giusti-Rodríguez
    • , Stephanie Godard
    • , Jacqueline I Goldstein
    • , Jacob Gratten
    • , Lieuwe de Haan
    • , Marian L Hamshere
    • , Mark Hansen
    • , Thomas Hansen
    • , Vahram Haroutunian
    • , Annette M Hartmann
    • , Frans A Henskens
    • , Stefan Herms
    • , Joel N Hirschhorn
    • , Per Hoffmann
    • , Andrea Hofman
    • , Hailiang Huang
    • , Masashi Ikeda
    • , Inge Joa
    • , Anna K Kähler
    • , René S Kahn
    • , Luba Kalaydjieva
    • , Juha Karjalainen
    • , David Kavanagh
    • , Matthew C Keller
    • , Brian J Kelly
    • , James L Kennedy
    • , Yunjung Kim
    • , James A Knowles
    • , Bettina Konte
    • , Claudine Laurent
    • , Phil Lee
    • , S Hong Lee
    • , Sophie E Legge
    • , Bernard Lerer
    • , Deborah L Levy
    • , Kung-Yee Liang
    • , Jeffrey Lieberman
    • , Jouko Lönnqvist
    • , Carmel M Loughland
    • , Patrik K E Magnusson
    • , Brion S Maher
    • , Wolfgang Maier
    • , Jacques Mallet
    • , Manuel Mattheisen
    • , Morten Mattingsdal
    • , Robert W McCarley
    • , Colm McDonald
    • , Andrew M McIntosh
    • , Sandra Meier
    • , Carin J Meijer
    • , Ingrid Melle
    • , Raquelle I Mesholam-Gately
    • , Andres Metspalu
    • , Patricia T Michie
    • , Lili Milani
    • , Vihra Milanova
    • , Younes Mokrab
    • , Derek W Morris
    • , Bertram Müller-Myhsok
    • , Kieran C Murphy
    • , Robin M Murray
    • , Inez Myin-Germeys
    • , Igor Nenadic
    • , Deborah A Nertney
    • , Gerald Nestadt
    • , Kristin K Nicodemus
    • , Laura Nisenbaum
    • , Annelie Nordin
    • , Eadbhard O'Callaghan
    • , Colm O'Dushlaine
    • , Sang-Yun Oh
    • , Ann Olincy
    • , Line Olsen
    • , F Anthony O'Neill
    • , Jim Van Os
    • , Christos Pantelis
    • , George N Papadimitriou
    • , Elena Parkhomenko
    • , Michele T Pato
    • , Tiina Paunio
    • , Psychosis Endophenotypes International Consortium
    • , Diana O Perkins
    • , Tune H Pers
    • , Olli Pietiläinen
    • , Jonathan Pimm
    • , Andrew J Pocklington
    • , John Powell
    • , Alkes Price
    • , Ann E Pulver
    • , Shaun M Purcell
    • , Digby Quested
    • , Henrik B Rasmussen
    • , Abraham Reichenberg
    • , Mark A Reimers
    • , Alexander L Richards
    • , Joshua L Roffman
    • , Panos Roussos
    • , Douglas M Ruderfer
    • , Veikko Salomaa
    • , Alan R Sanders
    • , Adam Savitz
    • , Ulrich Schall
    • , Thomas G Schulze
    • , Sibylle G Schwab
    • , Edward M Scolnick
    • , Rodney J Scott
    • , Larry J Seidman
    • , Jianxin Shi
    • , Jeremy M Silverman
    • , Jordan W Smoller
    • , Erik Söderman
    • , Chris C A Spencer
    • , Eli A Stahl
    • , Eric Strengman
    • , Jana Strohmaier
    • , T Scott Stroup
    • , Jaana Suvisaari
    • , Dragan M Svrakic
    • , Jin P Szatkiewicz
    • , Srinivas Thirumalai
    • , Paul A Tooney
    • , Juha Veijola
    • , Peter M Visscher
    • , John Waddington
    • , Dermot Walsh
    • , Bradley T Webb
    • , Mark Weiser
    • , Dieter B Wildenauer
    • , Nigel M Williams
    • , Stephanie Williams
    • , Stephanie H Witt
    • , Aaron R Wolen
    • , Brandon K Wormley
    • , Naomi R Wray
    • , Jing Qin Wu
    • , Clement C Zai
    • , Rolf Adolfsson
    • , Ole A Andreassen
    • , Douglas H R Blackwood
    • , Elvira Bramon
    • , Joseph D Buxbaum
    • , Sven Cichon
    • , David A Collier
    • , Aiden Corvin
    • , Mark J Daly
    • , Ariel Darvasi
    • , Enrico Domenici
    • , Tõnu Esko
    • , Pablo V Gejman
    • , Michael Gill
    • , Hugh Gurling
    • , Christina M Hultman
    • , Nakao Iwata
    • , Assen V Jablensky
    • , Erik G Jönsson
    • , Kenneth S Kendler
    • , George Kirov
    • , Jo Knight
    • , Douglas F Levinson
    • , Qingqin S Li
    • , Steven A McCarroll
    • , Andrew McQuillin
    • , Jennifer L Moran
    • , Bryan J Mowry
    • , Markus M Nöthen
    • , Roel A Ophoff
    • , Michael J Owen
    • , Aarno Palotie
    • , Carlos N Pato
    • , Tracey L Petryshen
    • , Danielle Posthuma
    • , Marcella Rietschel
    • , Brien P Riley
    • , Dan Rujescu
    • , Pamela Sklar
    • , David St Clair
    • , James T R Walters
    • , Thomas Werge
    • , Patrick F Sullivan
    • , Michael C O'Donovan
    • , Stephen W Scherer
    • , Benjamin M Neale
    • , Jonathan Sebat
    •  & CNV and Schizophrenia Working Groups of the Psychiatric Genomics Consortium
  • Article |

    Michael Talkowski and colleagues analyze balanced chromosomal abnormalities in 273 individuals by whole-genome sequencing. Their findings suggest that sequence-level resolution improves prediction of clinical outcomes for balanced rearrangements and provides insight into pathogenic mechanisms such as altered gene regulation due to changes in chromosome topology.

    • Claire Redin
    • , Harrison Brand
    • , Ryan L Collins
    • , Tammy Kammin
    • , Elyse Mitchell
    • , Jennelle C Hodge
    • , Carrie Hanscom
    • , Vamsee Pillalamarri
    • , Catarina M Seabra
    • , Mary-Alice Abbott
    • , Omar A Abdul-Rahman
    • , Erika Aberg
    • , Rhett Adley
    • , Sofia L Alcaraz-Estrada
    • , Fowzan S Alkuraya
    • , Yu An
    • , Mary-Anne Anderson
    • , Caroline Antolik
    • , Kwame Anyane-Yeboa
    • , Joan F Atkin
    • , Tina Bartell
    • , Jonathan A Bernstein
    • , Elizabeth Beyer
    • , Ian Blumenthal
    • , Ernie M H F Bongers
    • , Eva H Brilstra
    • , Chester W Brown
    • , Hennie T Brüggenwirth
    • , Bert Callewaert
    • , Colby Chiang
    • , Ken Corning
    • , Helen Cox
    • , Edwin Cuppen
    • , Benjamin B Currall
    • , Tom Cushing
    • , Dezso David
    • , Matthew A Deardorff
    • , Annelies Dheedene
    • , Marc D'Hooghe
    • , Bert B A de Vries
    • , Dawn L Earl
    • , Heather L Ferguson
    • , Heather Fisher
    • , David R FitzPatrick
    • , Pamela Gerrol
    • , Daniela Giachino
    • , Joseph T Glessner
    • , Troy Gliem
    • , Margo Grady
    • , Brett H Graham
    • , Cristin Griffis
    • , Karen W Gripp
    • , Andrea L Gropman
    • , Andrea Hanson-Kahn
    • , David J Harris
    • , Mark A Hayden
    • , Rosamund Hill
    • , Ron Hochstenbach
    • , Jodi D Hoffman
    • , Robert J Hopkin
    • , Monika W Hubshman
    • , A Micheil Innes
    • , Mira Irons
    • , Melita Irving
    • , Jessie C Jacobsen
    • , Sandra Janssens
    • , Tamison Jewett
    • , John P Johnson
    • , Marjolijn C Jongmans
    • , Stephen G Kahler
    • , David A Koolen
    • , Jerome Korzelius
    • , Peter M Kroisel
    • , Yves Lacassie
    • , William Lawless
    • , Emmanuelle Lemyre
    • , Kathleen Leppig
    • , Alex V Levin
    • , Haibo Li
    • , Hong Li
    • , Eric C Liao
    • , Cynthia Lim
    • , Edward J Lose
    • , Diane Lucente
    • , Michael J Macera
    • , Poornima Manavalan
    • , Giorgia Mandrile
    • , Carlo L Marcelis
    • , Lauren Margolin
    • , Tamara Mason
    • , Diane Masser-Frye
    • , Michael W McClellan
    • , Cinthya J Zepeda Mendoza
    • , Björn Menten
    • , Sjors Middelkamp
    • , Liya R Mikami
    • , Emily Moe
    • , Shehla Mohammed
    • , Tarja Mononen
    • , Megan E Mortenson
    • , Graciela Moya
    • , Aggie W Nieuwint
    • , Zehra Ordulu
    • , Sandhya Parkash
    • , Susan P Pauker
    • , Shahrin Pereira
    • , Danielle Perrin
    • , Katy Phelan
    • , Raul E Piña Aguilar
    • , Pino J Poddighe
    • , Giulia Pregno
    • , Salmo Raskin
    • , Linda Reis
    • , William Rhead
    • , Debra Rita
    • , Ivo Renkens
    • , Filip Roelens
    • , Jayla Ruliera
    • , Patrick Rump
    • , Samantha L P Schilit
    • , Ranad Shaheen
    • , Rebecca Sparkes
    • , Erica Spiegel
    • , Blair Stevens
    • , Matthew R Stone
    • , Julia Tagoe
    • , Joseph V Thakuria
    • , Bregje W van Bon
    • , Jiddeke van de Kamp
    • , Ineke van Der Burgt
    • , Ton van Essen
    • , Conny M van Ravenswaaij-Arts
    • , Markus J van Roosmalen
    • , Sarah Vergult
    • , Catharina M L Volker-Touw
    • , Dorothy P Warburton
    • , Matthew J Waterman
    • , Susan Wiley
    • , Anna Wilson
    • , Maria de la Concepcion A Yerena-de Vega
    • , Roberto T Zori
    • , Brynn Levy
    • , Han G Brunner
    • , Nicole de Leeuw
    • , Wigard P Kloosterman
    • , Erik C Thorland
    • , Cynthia C Morton
    • , James F Gusella
    •  & Michael E Talkowski

    Collection:

  • Article |

    Stuart Cook and colleagues study the role of TTN (titin)-truncating variants using a combination of heart physiology experiments in rats and genomic analysis in humans. Their data show that TTN variants are associated with a range of cardiac phenotypes in healthy individuals and in patients with dilated cardiomyopathy.

    • Sebastian Schafer
    • , Antonio de Marvao
    • , Eleonora Adami
    • , Lorna R Fiedler
    • , Benjamin Ng
    • , Ester Khin
    • , Owen J L Rackham
    • , Sebastiaan van Heesch
    • , Chee J Pua
    • , Miao Kui
    • , Roddy Walsh
    • , Upasana Tayal
    • , Sanjay K Prasad
    • , Timothy J W Dawes
    • , Nicole S J Ko
    • , David Sim
    • , Laura L H Chan
    • , Calvin W L Chin
    • , Francesco Mazzarotto
    • , Paul J Barton
    • , Franziska Kreuchwig
    • , Dominique P V de Kleijn
    • , Teresa Totman
    • , Carlo Biffi
    • , Nicole Tee
    • , Daniel Rueckert
    • , Valentin Schneider
    • , Allison Faber
    • , Vera Regitz-Zagrosek
    • , Jonathan G Seidman
    • , Christine E Seidman
    • , Wolfgang A Linke
    • , Jean-Paul Kovalik
    • , Declan O'Regan
    • , James S Ware
    • , Norbert Hubner
    •  & Stuart A Cook
  • Article |

    Thomas Hoffmann, Neil Risch and colleagues use longitudinal electronic health records from almost 100,000 individuals to conduct genome-wide association studies for blood pressure measurements. They find new significant loci that replicate in independent cohorts and can double the variance explained by using multiple blood pressure data points.

    • Thomas J Hoffmann
    • , Georg B Ehret
    • , Priyanka Nandakumar
    • , Dilrini Ranatunga
    • , Catherine Schaefer
    • , Pui-Yan Kwok
    • , Carlos Iribarren
    • , Aravinda Chakravarti
    •  & Neil Risch
  • Article |

    Hanno Glimm, Jan Korbel and colleagues present a computational framework called cis expression structural alteration mapping (CESAM), which they use to identify somatic copy-number alterations affecting cis-regulatory elements in cancer. They find that enhancer hijacking leads to overexpression of IRS4 and IGF2 in cancer.

    • Joachim Weischenfeldt
    • , Taronish Dubash
    • , Alexandros P Drainas
    • , Balca R Mardin
    • , Yuanyuan Chen
    • , Adrian M Stütz
    • , Sebastian M Waszak
    • , Graziella Bosco
    • , Ann Rita Halvorsen
    • , Benjamin Raeder
    • , Theocharis Efthymiopoulos
    • , Serap Erkek
    • , Christine Siegl
    • , Hermann Brenner
    • , Odd Terje Brustugun
    • , Sebastian M Dieter
    • , Paul A Northcott
    • , Iver Petersen
    • , Stefan M Pfister
    • , Martin Schneider
    • , Steinar K Solberg
    • , Erik Thunissen
    • , Wilko Weichert
    • , Thomas Zichner
    • , Roman Thomas
    • , Martin Peifer
    • , Aslaug Helland
    • , Claudia R Ball
    • , Martin Jechlinger
    • , Rocio Sotillo
    • , Hanno Glimm
    •  & Jan O Korbel
  • Article |

    Jian Hu and colleagues use mouse models to show that Qki deficiency promotes gliomagenesis by allowing neural stem cells to maintain their stemness outside the subventricular zone. Mechanistically, they show that Qki deficiency decreases endolysosome-mediated degradation of receptors that are essential for maintaining self-renewal, allowing cells to cope with low ligand levels outside of their niche.

    • Takashi Shingu
    • , Allen L Ho
    • , Liang Yuan
    • , Xin Zhou
    • , Congxin Dai
    • , Siyuan Zheng
    • , Qianghu Wang
    • , Yi Zhong
    • , Qing Chang
    • , James W Horner
    • , Brandon D Liebelt
    • , Yu Yao
    • , Baoli Hu
    • , Yiwen Chen
    • , Gregory N Fuller
    • , Roeland G W Verhaak
    • , Amy B Heimberger
    •  & Jian Hu
  • Article |

    Trever Bivona and colleagues use an in vivo lung cancer metastasis model to show that the transcriptional repressor Capicua (CIC) suppresses invasion and metastasis. CIC inactivation leads to upregulation of ETV4 and MMP24, which is necessary and sufficient for metastasis.

    • Ross A Okimoto
    • , Frank Breitenbuecher
    • , Victor R Olivas
    • , Wei Wu
    • , Beatrice Gini
    • , Matan Hofree
    • , Saurabh Asthana
    • , Gorjan Hrustanovic
    • , Jennifer Flanagan
    • , Asmin Tulpule
    • , Collin M Blakely
    • , Henry J Haringsma
    • , Andrew D Simmons
    • , Kyle Gowen
    • , James Suh
    • , Vincent A Miller
    • , Siraj Ali
    • , Martin Schuler
    •  & Trever G Bivona
  • Article |

    Sanjay Sinha and colleagues use a vascular model derived from human induced pluripotent stem cells from patients with Marfan syndrome with fibrillin-1 alterations to study aortic aneurysms. They find defects that mimic Marfan pathology as well as novel targets for treatment and can rescue the phenotype by correcting the mutation through genome editing.

    • Alessandra Granata
    • , Felipe Serrano
    • , William George Bernard
    • , Madeline McNamara
    • , Lucinda Low
    • , Priya Sastry
    •  & Sanjay Sinha
  • Article |

    Déborah Bourc’his and colleagues report that mouse embryos deficient for Liz (long isoform of Zdbf2) develop normally but fail to activate Zdbf2 in the postnatal brain and show growth reduction. These data suggest that transcription during an early embryonic stage may program a stable epigenetic state with later physiological consequences.

    • Maxim V C Greenberg
    • , Juliane Glaser
    • , Máté Borsos
    • , Fatima El Marjou
    • , Marius Walter
    • , Aurélie Teissandier
    •  & Déborah Bourc'his

Letters

  • Letter | | open

    Songlin Chen, Manfred Schartl, Qingyin Wang, Deborah M. Power and colleagues analyze the genome of the Japanese flounder and its transcriptome dynamics during metamorphosis. They report a role for thyroid hormone and retinoic acid signaling, as well as phototransduction pathways, in the regulation of craniofacial asymmetry.

    • Changwei Shao
    • , Baolong Bao
    • , Zhiyuan Xie
    • , Xinye Chen
    • , Bo Li
    • , Xiaodong Jia
    • , Qiulin Yao
    • , Guillermo Ortí
    • , Wenhui Li
    • , Xihong Li
    • , Kristin Hamre
    • , Juan Xu
    • , Lei Wang
    • , Fangyuan Chen
    • , Yongsheng Tian
    • , Alex M Schreiber
    • , Na Wang
    • , Fen Wei
    • , Jilin Zhang
    • , Zhongdian Dong
    • , Lei Gao
    • , Junwei Gai
    • , Takashi Sakamoto
    • , Sudong Mo
    • , Wenjun Chen
    • , Qiong Shi
    • , Hui Li
    • , Yunji Xiu
    • , Yangzhen Li
    • , Wenteng Xu
    • , Zhiyi Shi
    • , Guojie Zhang
    • , Deborah M Power
    • , Qingyin Wang
    • , Manfred Schartl
    •  & Songlin Chen
  • Letter |

    Audrey Chu, Matthew Steinhauser, Caroline Fox and colleagues report results of genome-wide association meta-analyses of ectopic-fat traits in individuals of European, African, Hispanic and Chinese ancestry. They identify seven new loci associated with ectopic-fat traits and present functional studies suggesting physiological roles for ATXN1 and UBE2E2 in adipogenesis.

    • Audrey Y Chu
    • , Xuan Deng
    • , Virginia A Fisher
    • , Alexander Drong
    • , Yang Zhang
    • , Mary F Feitosa
    • , Ching-Ti Liu
    • , Olivia Weeks
    • , Audrey C Choh
    • , Qing Duan
    • , Thomas D Dyer
    • , John D Eicher
    • , Xiuqing Guo
    • , Nancy L Heard-Costa
    • , Tim Kacprowski
    • , Jack W Kent Jr
    • , Leslie A Lange
    • , Xinggang Liu
    • , Kurt Lohman
    • , Lingyi Lu
    • , Anubha Mahajan
    • , Jeffrey R O'Connell
    • , Ankita Parihar
    • , Juan M Peralta
    • , Albert V Smith
    • , Yi Zhang
    • , Georg Homuth
    • , Ahmed H Kissebah
    • , Joel Kullberg
    • , René Laqua
    • , Lenore J Launer
    • , Matthias Nauck
    • , Michael Olivier
    • , Patricia A Peyser
    • , James G Terry
    • , Mary K Wojczynski
    • , Jie Yao
    • , Lawrence F Bielak
    • , John Blangero
    • , Ingrid B Borecki
    • , Donald W Bowden
    • , John Jeffrey Carr
    • , Stefan A Czerwinski
    • , Jingzhong Ding
    • , Nele Friedrich
    • , Vilmunder Gudnason
    • , Tamara B Harris
    • , Erik Ingelsson
    • , Andrew D Johnson
    • , Sharon L R Kardia
    • , Carl D Langefeld
    • , Lars Lind
    • , Yongmei Liu
    • , Braxton D Mitchell
    • , Andrew P Morris
    • , Thomas H Mosley Jr
    • , Jerome I Rotter
    • , Alan R Shuldiner
    • , Bradford Towne
    • , Henry Völzke
    • , Henri Wallaschofski
    • , James G Wilson
    • , Matthew Allison
    • , Cecilia M Lindgren
    • , Wolfram Goessling
    • , L Adrienne Cupples
    • , Matthew L Steinhauser
    •  & Caroline S Fox
  • Letter |

    Peter 't Hoen, Lude Franke, Bastiaan Heijmans and colleagues present a combined analysis of methylome and transcriptome data from a large collection of whole-blood samples to infer the downstream effects of disease-associated variants. They identify a large number of trait-associated SNPs influencing methylation of CpG sites in trans, providing insights into the downstream functional effects of many disease-associated variants.

    • Marc Jan Bonder
    • , René Luijk
    • , Daria V Zhernakova
    • , Matthijs Moed
    • , Patrick Deelen
    • , Martijn Vermaat
    • , Maarten van Iterson
    • , Freerk van Dijk
    • , Michiel van Galen
    • , Jan Bot
    • , Roderick C Slieker
    • , P Mila Jhamai
    • , Michael Verbiest
    • , H Eka D Suchiman
    • , Marijn Verkerk
    • , Ruud van der Breggen
    • , Jeroen van Rooij
    • , Nico Lakenberg
    • , Wibowo Arindrarto
    • , Szymon M Kielbasa
    • , Iris Jonkers
    • , Peter van 't Hof
    • , Irene Nooren
    • , Marian Beekman
    • , Joris Deelen
    • , Diana van Heemst
    • , Alexandra Zhernakova
    • , Ettje F Tigchelaar
    • , Morris A Swertz
    • , Albert Hofman
    • , André G Uitterlinden
    • , René Pool
    • , Jenny van Dongen
    • , Jouke J Hottenga
    • , Coen D A Stehouwer
    • , Carla J H van der Kallen
    • , Casper G Schalkwijk
    • , Leonard H van den Berg
    • , Erik W van Zwet
    • , Hailiang Mei
    • , Yang Li
    • , Mathieu Lemire
    • , Thomas J Hudson
    • , the BIOS Consortium
    • , P Eline Slagboom
    • , Cisca Wijmenga
    • , Jan H Veldink
    • , Marleen M J van Greevenbroek
    • , Cornelia M van Duijn
    • , Dorret I Boomsma
    • , Aaron Isaacs
    • , Rick Jansen
    • , Joyce B J van Meurs
    • , Peter A C 't Hoen
    • , Lude Franke
    •  & Bastiaan T Heijmans
  • Letter |

    Bastiaan Heijmans, Peter ’t Hoen, Lude Franke and colleagues describe a strategy to identify context-dependent expression quantitative trait loci (eQTLs). They apply their method to peripheral blood RNA–seq data from 2,116 unrelated individuals and discover 23,060 significant cis-regulated genes, of which 12% showed context-dependent eQTL effects.

    • Daria V Zhernakova
    • , Patrick Deelen
    • , Martijn Vermaat
    • , Maarten van Iterson
    • , Michiel van Galen
    • , Wibowo Arindrarto
    • , Peter van 't Hof
    • , Hailiang Mei
    • , Freerk van Dijk
    • , Harm-Jan Westra
    • , Marc Jan Bonder
    • , Jeroen van Rooij
    • , Marijn Verkerk
    • , P Mila Jhamai
    • , Matthijs Moed
    • , Szymon M Kielbasa
    • , Jan Bot
    • , Irene Nooren
    • , René Pool
    • , Jenny van Dongen
    • , Jouke J Hottenga
    • , Coen D A Stehouwer
    • , Carla J H van der Kallen
    • , Casper G Schalkwijk
    • , Alexandra Zhernakova
    • , Yang Li
    • , Ettje F Tigchelaar
    • , Niek de Klein
    • , Marian Beekman
    • , Joris Deelen
    • , Diana van Heemst
    • , Leonard H van den Berg
    • , Albert Hofman
    • , André G Uitterlinden
    • , Marleen M J van Greevenbroek
    • , Jan H Veldink
    • , Dorret I Boomsma
    • , Cornelia M van Duijn
    • , Cisca Wijmenga
    • , P Eline Slagboom
    • , Morris A Swertz
    • , Aaron Isaacs
    • , Joyce B J van Meurs
    • , Rick Jansen
    • , Bastiaan T Heijmans
    • , Peter A C 't Hoen
    •  & Lude Franke
  • Letter |

    Yoshitaka Fukada, Hikari Yoshitane and colleagues report that rhythmic expression of ADARB1, an RNA-editing enzyme that catalyzes adenosine-to-inosine conversion, controls mRNA oscillations in the mouse liver. Mice with Adarb1 mutations exhibit short-period rhythms in locomotor activity and gene expression.

    • Hideki Terajima
    • , Hikari Yoshitane
    • , Haruka Ozaki
    • , Yutaka Suzuki
    • , Shigeki Shimba
    • , Shinya Kuroda
    • , Wataru Iwasaki
    •  & Yoshitaka Fukada
  • Letter |

    Chi-Hua Chen and colleagues report a GWAS for five personality traits and identify four loci associated with extraversion and two associated with neuroticism at genome-wide significance. They find that the five personality traits are genetically correlated and identify genetic correlations between personality traits and psychiatric disorders.

    • Min-Tzu Lo
    • , David A Hinds
    • , Joyce Y Tung
    • , Carol Franz
    • , Chun-Chieh Fan
    • , Yunpeng Wang
    • , Olav B Smeland
    • , Andrew Schork
    • , Dominic Holland
    • , Karolina Kauppi
    • , Nilotpal Sanyal
    • , Valentina Escott-Price
    • , Daniel J Smith
    • , Michael O'Donovan
    • , Hreinn Stefansson
    • , Gyda Bjornsdottir
    • , Thorgeir E Thorgeirsson
    • , Kari Stefansson
    • , Linda K McEvoy
    • , Anders M Dale
    • , Ole A Andreassen
    •  & Chi-Hua Chen
  • Letter |

    Thorsten Schnurbusch, Helmy Youssef and colleagues show that VRS2, a transcription factor of the SHI family, regulates floral organ patterning and phase duration during spike development in barley. Their data establish a link between the SHI protein family and sucrose metabolism during organ growth and development.

    • Helmy M Youssef
    • , Kai Eggert
    • , Ravi Koppolu
    • , Ahmad M Alqudah
    • , Naser Poursarebani
    • , Arash Fazeli
    • , Shun Sakuma
    • , Akemi Tagiri
    • , Twan Rutten
    • , Geetha Govind
    • , Udda Lundqvist
    • , Andreas Graner
    • , Takao Komatsuda
    • , Nese Sreenivasulu
    •  & Thorsten Schnurbusch
  • Letter |

    Zachary Lippman, José Jiménez-Gómez and colleagues show that cultivated tomatoes have lost day-length-sensitive flowering, compared to their wild relatives, as a result of cis-regulatory variation affecting expression of SP5G, a paralog of the florigen gene SFT. They engineered SP5G loss-of-function mutant plants, resulting in rapid flowering and early yield.

    • Sebastian Soyk
    • , Niels A Müller
    • , Soon Ju Park
    • , Inga Schmalenbach
    • , Ke Jiang
    • , Ryosuke Hayama
    • , Lei Zhang
    • , Joyce Van Eck
    • , José M Jiménez-Gómez
    •  & Zachary B Lippman