Volume 49 Issue 9, 1 September 2017

Correspondence

Letter

  • Letter |

    Hugh Watkins and colleagues meta-analyze data from the UK Biobank along with recent genome-wide association studies for coronary artery disease. They identify 13 new loci that were genome-wide significant and 243 loci at a 5% false discovery rate.

    • Christopher P Nelson
    • , Anuj Goel
    • , Adam S Butterworth
    • , Stavroula Kanoni
    • , Tom R Webb
    • , Eirini Marouli
    • , Lingyao Zeng
    • , Ioanna Ntalla
    • , Florence Y Lai
    • , Jemma C Hopewell
    • , Olga Giannakopoulou
    • , Tao Jiang
    • , Stephen E Hamby
    • , Emanuele Di Angelantonio
    • , Themistocles L Assimes
    • , Erwin P Bottinger
    • , John C Chambers
    • , Robert Clarke
    • , Colin N A Palmer
    • , Richard M Cubbon
    • , Patrick Ellinor
    • , Raili Ermel
    • , Evangelos Evangelou
    • , Paul W Franks
    • , Christopher Grace
    • , Dongfeng Gu
    • , Aroon D Hingorani
    • , Joanna M M Howson
    • , Erik Ingelsson
    • , Adnan Kastrati
    • , Thorsten Kessler
    • , Theodosios Kyriakou
    • , Terho Lehtimäki
    • , Xiangfeng Lu
    • , Yingchang Lu
    • , Winfried März
    • , Ruth McPherson
    • , Andres Metspalu
    • , Mar Pujades-Rodriguez
    • , Arno Ruusalepp
    • , Eric E Schadt
    • , Amand F Schmidt
    • , Michael J Sweeting
    • , Pierre A Zalloua
    • , Kamal AlGhalayini
    • , Bernard D Keavney
    • , Jaspal S Kooner
    • , Ruth J F Loos
    • , Riyaz S Patel
    • , Martin K Rutter
    • , Maciej Tomaszewski
    • , Ioanna Tzoulaki
    • , Eleftheria Zeggini
    • , Jeanette Erdmann
    • , George Dedoussis
    • , Johan L M Björkegren
    • , EPIC-CVD Consortium
    • , CARDIoGRAMplusC4D
    • , The UK Biobank CardioMetabolic Consortium CHD working group
    • , Heribert Schunkert
    • , Martin Farrall
    • , John Danesh
    • , Nilesh J Samani
    • , Hugh Watkins
    •  & Panos Deloukas
  • Letter |

    Sekar Kathiresan and colleagues perform a genome-wide association test for coronary artery disease (CAD) using data from the UK Biobank. They identify 15 new loci and perform phenome-wide association scanning, implicating insulin resistance pathways and transendothelial migration of leukocytes in CAD.

    • Derek Klarin
    • , Qiuyu Martin Zhu
    • , Connor A Emdin
    • , Mark Chaffin
    • , Steven Horner
    • , Brian J McMillan
    • , Alison Leed
    • , Michael E Weale
    • , Chris C A Spencer
    • , François Aguet
    • , Ayellet V Segrè
    • , Kristin G Ardlie
    • , Amit V Khera
    • , Virendar K Kaushik
    • , Pradeep Natarajan
    • , CARDIoGRAMplusC4D Consortium
    •  & Sekar Kathiresan
  • Letter |

    Sven van der Lee, Julie Williams, Gerard Schellenberg and colleagues identify rare coding variants in PLCG2, ABI3 and TREM2 associated with Alzheimer's disease. These genes are highly expressed in microglia and provide additional evidence that the microglia-mediated immune response contributes to the development of Alzheimer's disease.

    • Rebecca Sims
    • , Sven J van der Lee
    • , Adam C Naj
    • , Céline Bellenguez
    • , Nandini Badarinarayan
    • , Johanna Jakobsdottir
    • , Brian W Kunkle
    • , Anne Boland
    • , Rachel Raybould
    • , Joshua C Bis
    • , Eden R Martin
    • , Benjamin Grenier-Boley
    • , Stefanie Heilmann-Heimbach
    • , Vincent Chouraki
    • , Amanda B Kuzma
    • , Kristel Sleegers
    • , Maria Vronskaya
    • , Agustin Ruiz
    • , Robert R Graham
    • , Robert Olaso
    • , Per Hoffmann
    • , Megan L Grove
    • , Badri N Vardarajan
    • , Mikko Hiltunen
    • , Markus M Nöthen
    • , Charles C White
    • , Kara L Hamilton-Nelson
    • , Jacques Epelbaum
    • , Wolfgang Maier
    • , Seung-Hoan Choi
    • , Gary W Beecham
    • , Cécile Dulary
    • , Stefan Herms
    • , Albert V Smith
    • , Cory C Funk
    • , Céline Derbois
    • , Andreas J Forstner
    • , Shahzad Ahmad
    • , Hongdong Li
    • , Delphine Bacq
    • , Denise Harold
    • , Claudia L Satizabal
    • , Otto Valladares
    • , Alessio Squassina
    • , Rhodri Thomas
    • , Jennifer A Brody
    • , Liming Qu
    • , Pascual Sánchez-Juan
    • , Taniesha Morgan
    • , Frank J Wolters
    • , Yi Zhao
    • , Florentino Sanchez Garcia
    • , Nicola Denning
    • , Myriam Fornage
    • , John Malamon
    • , Maria Candida Deniz Naranjo
    • , Elisa Majounie
    • , Thomas H Mosley
    • , Beth Dombroski
    • , David Wallon
    • , Michelle K Lupton
    • , Josée Dupuis
    • , Patrice Whitehead
    • , Laura Fratiglioni
    • , Christopher Medway
    • , Xueqiu Jian
    • , Shubhabrata Mukherjee
    • , Lina Keller
    • , Kristelle Brown
    • , Honghuang Lin
    • , Laura B Cantwell
    • , Francesco Panza
    • , Bernadette McGuinness
    • , Sonia Moreno-Grau
    • , Jeremy D Burgess
    • , Vincenzo Solfrizzi
    • , Petra Proitsi
    • , Hieab H Adams
    • , Mariet Allen
    • , Davide Seripa
    • , Pau Pastor
    • , L Adrienne Cupples
    • , Nathan D Price
    • , Didier Hannequin
    • , Ana Frank-García
    • , Daniel Levy
    • , Paramita Chakrabarty
    • , Paolo Caffarra
    • , Ina Giegling
    • , Alexa S Beiser
    • , Vilmantas Giedraitis
    • , Harald Hampel
    • , Melissa E Garcia
    • , Xue Wang
    • , Lars Lannfelt
    • , Patrizia Mecocci
    • , Gudny Eiriksdottir
    • , Paul K Crane
    • , Florence Pasquier
    • , Virginia Boccardi
    • , Isabel Henández
    • , Robert C Barber
    • , Martin Scherer
    • , Lluis Tarraga
    • , Perrie M Adams
    • , Markus Leber
    • , Yuning Chen
    • , Marilyn S Albert
    • , Steffi Riedel-Heller
    • , Valur Emilsson
    • , Duane Beekly
    • , Anne Braae
    • , Reinhold Schmidt
    • , Deborah Blacker
    • , Carlo Masullo
    • , Helena Schmidt
    • , Rachelle S Doody
    • , Gianfranco Spalletta
    • , W T Longstreth Jr
    • , Thomas J Fairchild
    • , Paola Bossù
    • , Oscar L Lopez
    • , Matthew P Frosch
    • , Eleonora Sacchinelli
    • , Bernardino Ghetti
    • , Qiong Yang
    • , Ryan M Huebinger
    • , Frank Jessen
    • , Shuo Li
    • , M Ilyas Kamboh
    • , John Morris
    • , Oscar Sotolongo-Grau
    • , Mindy J Katz
    • , Chris Corcoran
    • , Melanie Dunstan
    • , Amy Braddel
    • , Charlene Thomas
    • , Alun Meggy
    • , Rachel Marshall
    • , Amy Gerrish
    • , Jade Chapman
    • , Miquel Aguilar
    • , Sarah Taylor
    • , Matt Hill
    • , Mònica Díez Fairén
    • , Angela Hodges
    • , Bruno Vellas
    • , Hilkka Soininen
    • , Iwona Kloszewska
    • , Makrina Daniilidou
    • , James Uphill
    • , Yogen Patel
    • , Joseph T Hughes
    • , Jenny Lord
    • , James Turton
    • , Annette M Hartmann
    • , Roberta Cecchetti
    • , Chiara Fenoglio
    • , Maria Serpente
    • , Marina Arcaro
    • , Carlo Caltagirone
    • , Maria Donata Orfei
    • , Antonio Ciaramella
    • , Sabrina Pichler
    • , Manuel Mayhaus
    • , Wei Gu
    • , Alberto Lleó
    • , Juan Fortea
    • , Rafael Blesa
    • , Imelda S Barber
    • , Keeley Brookes
    • , Chiara Cupidi
    • , Raffaele Giovanni Maletta
    • , David Carrell
    • , Sandro Sorbi
    • , Susanne Moebus
    • , Maria Urbano
    • , Alberto Pilotto
    • , Johannes Kornhuber
    • , Paolo Bosco
    • , Stephen Todd
    • , David Craig
    • , Janet Johnston
    • , Michael Gill
    • , Brian Lawlor
    • , Aoibhinn Lynch
    • , Nick C Fox
    • , John Hardy
    • , ARUK Consortium
    • , Roger L Albin
    • , Liana G Apostolova
    • , Steven E Arnold
    • , Sanjay Asthana
    • , Craig S Atwood
    • , Clinton T Baldwin
    • , Lisa L Barnes
    • , Sandra Barral
    • , Thomas G Beach
    • , James T Becker
    • , Eileen H Bigio
    • , Thomas D Bird
    • , Bradley F Boeve
    • , James D Bowen
    • , Adam Boxer
    • , James R Burke
    • , Jeffrey M Burns
    • , Joseph D Buxbaum
    • , Nigel J Cairns
    • , Chuanhai Cao
    • , Chris S Carlson
    • , Cynthia M Carlsson
    • , Regina M Carney
    • , Minerva M Carrasquillo
    • , Steven L Carroll
    • , Carolina Ceballos Diaz
    • , Helena C Chui
    • , David G Clark
    • , David H Cribbs
    • , Elizabeth A Crocco
    • , Charles DeCarli
    • , Malcolm Dick
    • , Ranjan Duara
    • , Denis A Evans
    • , Kelley M Faber
    • , Kenneth B Fallon
    • , David W Fardo
    • , Martin R Farlow
    • , Steven Ferris
    • , Tatiana M Foroud
    • , Douglas R Galasko
    • , Marla Gearing
    • , Daniel H Geschwind
    • , John R Gilbert
    • , Neill R Graff-Radford
    • , Robert C Green
    • , John H Growdon
    • , Ronald L Hamilton
    • , Lindy E Harrell
    • , Lawrence S Honig
    • , Matthew J Huentelman
    • , Christine M Hulette
    • , Bradley T Hyman
    • , Gail P Jarvik
    • , Erin Abner
    • , Lee-Way Jin
    • , Gyungah Jun
    • , Anna Karydas
    • , Jeffrey A Kaye
    • , Ronald Kim
    • , Neil W Kowall
    • , Joel H Kramer
    • , Frank M LaFerla
    • , James J Lah
    • , James B Leverenz
    • , Allan I Levey
    • , Ge Li
    • , Andrew P Lieberman
    • , Kathryn L Lunetta
    • , Constantine G Lyketsos
    • , Daniel C Marson
    • , Frank Martiniuk
    • , Deborah C Mash
    • , Eliezer Masliah
    • , Wayne C McCormick
    • , Susan M McCurry
    • , Andrew N McDavid
    • , Ann C McKee
    • , Marsel Mesulam
    • , Bruce L Miller
    • , Carol A Miller
    • , Joshua W Miller
    • , John C Morris
    • , Jill R Murrell
    • , Amanda J Myers
    • , Sid O'Bryant
    • , John M Olichney
    • , Vernon S Pankratz
    • , Joseph E Parisi
    • , Henry L Paulson
    • , William Perry
    • , Elaine Peskind
    • , Aimee Pierce
    • , Wayne W Poon
    • , Huntington Potter
    • , Joseph F Quinn
    • , Ashok Raj
    • , Murray Raskind
    • , Barry Reisberg
    • , Christiane Reitz
    • , John M Ringman
    • , Erik D Roberson
    • , Ekaterina Rogaeva
    • , Howard J Rosen
    • , Roger N Rosenberg
    • , Mark A Sager
    • , Andrew J Saykin
    • , Julie A Schneider
    • , Lon S Schneider
    • , William W Seeley
    • , Amanda G Smith
    • , Joshua A Sonnen
    • , Salvatore Spina
    • , Robert A Stern
    • , Russell H Swerdlow
    • , Rudolph E Tanzi
    • , Tricia A Thornton-Wells
    • , John Q Trojanowski
    • , Juan C Troncoso
    • , Vivianna M Van Deerlin
    • , Linda J Van Eldik
    • , Harry V Vinters
    • , Jean Paul Vonsattel
    • , Sandra Weintraub
    • , Kathleen A Welsh-Bohmer
    • , Kirk C Wilhelmsen
    • , Jennifer Williamson
    • , Thomas S Wingo
    • , Randall L Woltjer
    • , Clinton B Wright
    • , Chang-En Yu
    • , Lei Yu
    • , Fabienne Garzia
    • , Feroze Golamaully
    • , Gislain Septier
    • , Sebastien Engelborghs
    • , Rik Vandenberghe
    • , Peter P De Deyn
    • , Carmen Muñoz Fernadez
    • , Yoland Aladro Benito
    • , Hakan Thonberg
    • , Charlotte Forsell
    • , Lena Lilius
    • , Anne Kinhult-Stählbom
    • , Lena Kilander
    • , RoseMarie Brundin
    • , Letizia Concari
    • , Seppo Helisalmi
    • , Anne Maria Koivisto
    • , Annakaisa Haapasalo
    • , Vincent Dermecourt
    • , Nathalie Fievet
    • , Olivier Hanon
    • , Carole Dufouil
    • , Alexis Brice
    • , Karen Ritchie
    • , Bruno Dubois
    • , Jayanadra J Himali
    • , C Dirk Keene
    • , JoAnn Tschanz
    • , Annette L Fitzpatrick
    • , Walter A Kukull
    • , Maria Norton
    • , Thor Aspelund
    • , Eric B Larson
    • , Ron Munger
    • , Jerome I Rotter
    • , Richard B Lipton
    • , María J Bullido
    • , Albert Hofman
    • , Thomas J Montine
    • , Eliecer Coto
    • , Eric Boerwinkle
    • , Ronald C Petersen
    • , Victoria Alvarez
    • , Fernando Rivadeneira
    • , Eric M Reiman
    • , Maura Gallo
    • , Christopher J O'Donnell
    • , Joan S Reisch
    • , Amalia Cecilia Bruni
    • , Donald R Royall
    • , Martin Dichgans
    • , Mary Sano
    • , Daniela Galimberti
    • , Peter St George-Hyslop
    • , Elio Scarpini
    • , Debby W Tsuang
    • , Michelangelo Mancuso
    • , Ubaldo Bonuccelli
    • , Ashley R Winslow
    • , Antonio Daniele
    • , Chuang-Kuo Wu
    • , GERAD/PERADES, CHARGE, ADGC, EADI
    • , Oliver Peters
    • , Benedetta Nacmias
    • , Matthias Riemenschneider
    • , Reinhard Heun
    • , Carol Brayne
    • , David C Rubinsztein
    • , Jose Bras
    • , Rita Guerreiro
    • , Ammar Al-Chalabi
    • , Christopher E Shaw
    • , John Collinge
    • , David Mann
    • , Magda Tsolaki
    • , Jordi Clarimón
    • , Rebecca Sussams
    • , Simon Lovestone
    • , Michael C O'Donovan
    • , Michael J Owen
    • , Timothy W Behrens
    • , Simon Mead
    • , Alison M Goate
    • , Andre G Uitterlinden
    • , Clive Holmes
    • , Carlos Cruchaga
    • , Martin Ingelsson
    • , David A Bennett
    • , John Powell
    • , Todd E Golde
    • , Caroline Graff
    • , Philip L De Jager
    • , Kevin Morgan
    • , Nilufer Ertekin-Taner
    • , Onofre Combarros
    • , Bruce M Psaty
    • , Peter Passmore
    • , Steven G Younkin
    • , Claudine Berr
    • , Vilmundur Gudnason
    • , Dan Rujescu
    • , Dennis W Dickson
    • , Jean-François Dartigues
    • , Anita L DeStefano
    • , Sara Ortega-Cubero
    • , Hakon Hakonarson
    • , Dominique Campion
    • , Merce Boada
    • , John Keoni Kauwe
    • , Lindsay A Farrer
    • , Christine Van Broeckhoven
    • , M Arfan Ikram
    • , Lesley Jones
    • , Jonathan L Haines
    • , Christophe Tzourio
    • , Lenore J Launer
    • , Valentina Escott-Price
    • , Richard Mayeux
    • , Jean-François Deleuze
    • , Najaf Amin
    • , Peter A Holmans
    • , Margaret A Pericak-Vance
    • , Philippe Amouyel
    • , Cornelia M van Duijn
    • , Alfredo Ramirez
    • , Li-San Wang
    • , Jean-Charles Lambert
    • , Sudha Seshadri
    • , Julie Williams
    •  & Gerard D Schellenberg
  • Letter |

    Kumarasamy Thangaraj, David Reich and colleagues identify 81 South Asian groups descended from extreme founder events, including 14 with a census size of over 1 million people, thus providing an opportunity to test for and decrease the burden of recessive genetic diseases in these populations.

    • Nathan Nakatsuka
    • , Priya Moorjani
    • , Niraj Rai
    • , Biswanath Sarkar
    • , Arti Tandon
    • , Nick Patterson
    • , Gandham SriLakshmi Bhavani
    • , Katta Mohan Girisha
    • , Mohammed S Mustak
    • , Sudha Srinivasan
    • , Amit Kaushik
    • , Saadi Abdul Vahab
    • , Sujatha M Jagadeesh
    • , Kapaettu Satyamoorthy
    • , Lalji Singh
    • , David Reich
    •  & Kumarasamy Thangaraj
  • Letter |

    Isabelle Janoueix-Lerosey, Valentina Boeva and colleagues analyze the super-enhancer landscape of 25 neuroblastoma cell lines to define core regulatory circuits controlling gene expression programs. They find and functionally characterize two types of cell identity that contribute to the tumor heterogeneity of neuroblastoma.

    • Valentina Boeva
    • , Caroline Louis-Brennetot
    • , Agathe Peltier
    • , Simon Durand
    • , Cécile Pierre-Eugène
    • , Virginie Raynal
    • , Heather C Etchevers
    • , Sophie Thomas
    • , Alban Lermine
    • , Estelle Daudigeos-Dubus
    • , Birgit Geoerger
    • , Martin F Orth
    • , Thomas G P Grünewald
    • , Elise Diaz
    • , Bertrand Ducos
    • , Didier Surdez
    • , Angel M Carcaboso
    • , Irina Medvedeva
    • , Thomas Deller
    • , Valérie Combaret
    • , Eve Lapouble
    • , Gaelle Pierron
    • , Sandrine Grossetête-Lalami
    • , Sylvain Baulande
    • , Gudrun Schleiermacher
    • , Emmanuel Barillot
    • , Hermann Rohrer
    • , Olivier Delattre
    •  & Isabelle Janoueix-Lerosey
  • Letter |

    Daniel Gudbjartsson, Kari Stefansson and colleagues assess the effect of variants associated with mean fasting glucose levels on the variance in fasting glucose levels. They find that variants that increase both the levels and variance of fasting glucose increase type 2 diabetes risk, whereas those that increase the levels but reduce the variance do not.

    • Erna V Ivarsdottir
    • , Valgerdur Steinthorsdottir
    • , Maryam S Daneshpour
    • , Gudmar Thorleifsson
    • , Patrick Sulem
    • , Hilma Holm
    • , Snaevar Sigurdsson
    • , Astradur B Hreidarsson
    • , Gunnar Sigurdsson
    • , Ragnar Bjarnason
    • , Arni V Thorsson
    • , Rafn Benediktsson
    • , Gudmundur Eyjolfsson
    • , Olof Sigurdardottir
    • , Isleifur Olafsson
    • , Sirous Zeinali
    • , Fereidoun Azizi
    • , Unnur Thorsteinsdottir
    • , Daniel F Gudbjartsson
    •  & Kari Stefansson

Article

  • Article |

    Peter Balint-Kurti, Qin Yang and colleagues report that ZmCCoAOMT2, which encodes a caffeoyl-CoA O-methyltransferase, is a gene within the quantitative trait locus qMdr9.02, which confers resistance to southern leaf blight and gray leaf spot. Their findings suggest that resistance might be caused by differences in levels of lignin and other metabolites in the phenylpropanoid pathway.

    • Qin Yang
    • , Yijian He
    • , Mercy Kabahuma
    • , Timothy Chaya
    • , Amy Kelly
    • , Eli Borrego
    • , Yang Bian
    • , Farid El Kasmi
    • , Li Yang
    • , Paulo Teixeira
    • , Judith Kolkman
    • , Rebecca Nelson
    • , Michael Kolomiets
    • , Jeffery L Dangl
    • , Randall Wisser
    • , Jeffrey Caplan
    • , Xu Li
    • , Nick Lauter
    •  & Peter Balint-Kurti
  • Article |

    Ernesto Guccione and colleagues report that the transcription factor PRDM15 regulates naive pluripotency in mouse embryos and embryonic stem cells and in derivation of mouse and human iPSCs. They further show that PRDM15 promotes WNT signaling and inhibits MAPK–ERK signaling by directly regulating the expression of R-spondin1 and Sprouty1, respectively.

    • Slim Mzoughi
    • , Jingxian Zhang
    • , Delphine Hequet
    • , Shun Xie Teo
    • , Haitong Fang
    • , Qiao Rui Xing
    • , Marco Bezzi
    • , Michelle Kay Yi Seah
    • , Sheena L M Ong
    • , Eun Myoung Shin
    • , Heike Wollmann
    • , Esther S M Wong
    • , Muthafar Al-Haddawi
    • , Colin L Stewart
    • , Vinay Tergaonkar
    • , Yuin-Han Loh
    • , N Ray Dunn
    • , Daniel M Messerschmidt
    •  & Ernesto Guccione
  • Article |

    Kevin Brown and colleagues functionally characterize a melanoma risk locus encompassing PARP1, correlating the risk genotype to PARP1 gene expression levels in melanoma cells. They identify an intronic gene-regulatory variant in PARP1 and find that PARP1 can promote cell proliferation and rescue oncogene-induced senescence, likely through MITF.

    • Jiyeon Choi
    • , Mai Xu
    • , Matthew M Makowski
    • , Tongwu Zhang
    • , Matthew H Law
    • , Michael A Kovacs
    • , Anton Granzhan
    • , Wendy J Kim
    • , Hemang Parikh
    • , Michael Gartside
    • , Jeffrey M Trent
    • , Marie-Paule Teulade-Fichou
    • , Mark M Iles
    • , Julia A Newton-Bishop
    • , D Timothy Bishop
    • , Stuart MacGregor
    • , Nicholas K Hayward
    • , Michiel Vermeulen
    •  & Kevin M Brown
  • Article |

    Henry Sucov and colleagues demonstrate substantial natural variation in the capacity of the mouse heart to regenerate after injury and link this to the prevalence of mononuclear diploid cardiomyocytes. They identify Tnni3k as one gene that contributes to the observed variation and validate its role through mouse knockout and zebrafish overexpression studies.

    • Michaela Patterson
    • , Lindsey Barske
    • , Ben Van Handel
    • , Christoph D Rau
    • , Peiheng Gan
    • , Avneesh Sharma
    • , Shan Parikh
    • , Matt Denholtz
    • , Ying Huang
    • , Yukiko Yamaguchi
    • , Hua Shen
    • , Hooman Allayee
    • , J Gage Crump
    • , Thomas I Force
    • , Ching-Ling Lien
    • , Takako Makita
    • , Aldons J Lusis
    • , S Ram Kumar
    •  & Henry M Sucov
  • Article |

    Mathieu Lupien and colleagues analyze data from primary prostate tumors with and without TMPRSS2–ERG (T2E) rearrangements. They find that in T2E tumors, there is a distinct regulatory landscape resulting from the co-option of transcription factors by ERG which causes dependency on NOTCH signaling.

    • Ken J Kron
    • , Alexander Murison
    • , Stanley Zhou
    • , Vincent Huang
    • , Takafumi N Yamaguchi
    • , Yu-Jia Shiah
    • , Michael Fraser
    • , Theodorus van der Kwast
    • , Paul C Boutros
    • , Robert G Bristow
    •  & Mathieu Lupien

Perspective

  • Perspective |

    Wayne Powell and colleagues compare the different tools and approaches used by the plant breeding community versus the animal breeding community for crop and livestock improvement. They argue that the two disciplines can be united via adoption of genomic selection along with the exchange of resources and techniques between the two areas.

    • John M Hickey
    • , Tinashe Chiurugwi
    • , Ian Mackay
    • , Wayne Powell
    • , Implementing Genomic Selection in CGIAR Breeding Programs Workshop Participants
    • , John M Hickey
    • , Tinashe Chiurugwi
    • , Ian Mackay
    • , Wayne Powell
    • , Andre Eggen
    • , Andrzej Kilian
    • , Chris Jones
    • , Claudia Canales
    • , Dario Grattapaglia
    • , Filippo Bassi
    • , Gary Atlin
    • , Gregor Gorjanc
    • , Ian Dawson
    • , Ismail Rabbi
    • , Jean-Marcel Ribaut
    • , Jessica Rutkoski
    • , John Benzie
    • , Jon Lightner
    • , Joram Mwacharo
    • , Joris Parmentier
    • , Kelly Robbins
    • , Leif Skot
    • , Marnin Wolfe
    • , Mathieu Rouard
    • , Matt Clark
    • , Peter Amer
    • , Peter Gardiner
    • , Prasad Hendre
    • , Raphael Mrode
    • , Shoba Sivasankar
    • , Søren Rasmussen
    • , Susanne Groh
    • , Vicky Jackson
    • , William Thomas
    •  & Yoseph Beyene
  • Perspective |

    Jian Yang and colleagues explore the uses and abuses of heritability estimates derived from pedigrees and from GWAS SNPs and make recommendations for best practice in future applications of SNP-based heritability.

    • Jian Yang
    • , Jian Zeng
    • , Michael E Goddard
    • , Naomi R Wray
    •  & Peter M Visscher

Analysis

  • Analysis |

    Gil McVean and colleagues present a new Bayesian analysis framework that exploits the hierarchical structure of diagnosis classifications to analyze genetic variants against UK Biobank disease phenotypes derived from self-reporting and hospital episode statistics. Their method displays increased power to detect genetic effects over other approaches and identifies novel associations between classical HLA alleles and common immune-mediated diseases.

    • Adrian Cortes
    • , Calliope A Dendrou
    • , Allan Motyer
    • , Luke Jostins
    • , Damjan Vukcevic
    • , Alexander Dilthey
    • , Peter Donnelly
    • , Stephen Leslie
    • , Lars Fugger
    •  & Gil McVean
  • Analysis |

    Andrey Rzhetsky and colleagues analyze electronic medical records from over one-third of the US population to estimate disease heritability and to determine the genetic and environmental contributions to disease variance. They obtain 84 new heritability estimates and find that the genetic correlation values for disease pairs differ from their environmental correlation values.

    • Kanix Wang
    • , Hallie Gaitsch
    • , Hoifung Poon
    • , Nancy J Cox
    •  & Andrey Rzhetsky

News & Views

  • News & Views |

    Genetic and functional analyses of 120 mouse strains have identified a heart regeneration candidate gene that modulates the contractile sarcomeric apparatus. This gene, Tnni3k, controls the frequency of the mononuclear, diploid cardiomyocyte population, which affects cardiomyocyte proliferative potential after injury.

    • Ana Vujic
    • , Vinícius Bassaneze
    •  & Richard T Lee
  • News & Views |

    ERG overexpression in prostate cancers promotes the development of widespread changes in gene expression and chromatin landscapes, leading to redistribution of key transcription factors in prostate cancers positive for the TMPRSS2-ERG fusion gene. The overexpression of ERG is further assisted by the development of a super-enhancer in the ERG locus.

    • Deepak Babu
    •  & Melissa J Fullwood
  • News & Views |

    An innovative study analyzing genetic association across tree-structured routine healthcare data in the UK Biobank represents a new branch on a tree that is poised to grow rapidly and offer new kinds of insights on how genome variation relates to human health and disease. Indeed, this tree is likely to offer new kinds of insights into the very nature of human disease.

    • Nancy J Cox

Editorial

  • Editorial |

    A solution to screening for recessive heritable disorders and identifying genetic influences on common diseases is to be found in the history of one of the world's most populous regions. Large South Asian populations are a mosaic of smaller populations, many of which have founder effects as extreme as those in the European isolates that first inspired genetic medicine.