Multiancestry association study identifies new asthma risk loci that colocalize with immune-cell enhancer marks.

Nat Genet
Authors
Florence Demenais
Patricia Margaritte-Jeannin
Kathleen Barnes
William Cookson
Janine Altmüller
Wei Ang
R Graham Barr
Terri Beaty
Allan Becker
John Beilby
Hans Bisgaard
Unnur Bjornsdottir
Eugene Bleecker
Klaus Bønnelykke
Dorret Boomsma
Emmanuelle Bouzigon
Christopher Brightling
Myriam Brossard
Guy Brusselle
Esteban Burchard
Kristin Burkart
Andrew Bush
Moira Chan-Yeung
Kian Chung
Alexessander Alves
John Curtin
Adnan Custovic
Denise Daley
Johan de Jongste
Blanca Del-Rio-Navarro
Kathleen Donohue
Liesbeth Duijts
Celeste Eng
Johan Eriksson
Martin Farrall
Yuliya Fedorova
Bjarke Feenstra
Manuel Ferreira
Australian Asthma Genetics Consortium (AAGC) collaborators
Maxim Freidin
Zofia Gajdos
Jim Gauderman
Ulrike Gehring
Frank Geller
Jon Genuneit
Sina Gharib
Frank Gilliland
Raquel Granell
Penelope Graves
Daniel Gudbjartsson
Tari Haahtela
Susan Heckbert
Dick Heederik
Joachim Heinrich
Markku Heliövaara
John Henderson
Blanca Himes
Hiroshi Hirose
Joel Hirschhorn
Albert Hofman
Patrick Holt
Jouke Hottenga
Thomas Hudson
Jennie Hui
Medea Imboden
Vladimir Ivanov
Vincent Jaddoe
Alan James
Christer Janson
Marjo-Riitta Jarvelin
Deborah Jarvis
Graham Jones
Ingileif Jonsdottir
Pekka Jousilahti
Michael Kabesch
Mika Kähönen
David Kantor
Alexandra Karunas
Elza Khusnutdinova
Gerard Koppelman
Anita Kozyrskyj
Eskil Kreiner
Michiaki Kubo
Rajesh Kumar
Ashish Kumar
Mikko Kuokkanen
Lies Lahousse
Tarja Laitinen
Catherine Laprise
Mark Lathrop
Susanne Lau
Young-Ae Lee
Terho Lehtimäki
Sébastien Letort
Albert Levin
Guo Li
Liming Liang
Laura Loehr
Stephanie London
Daan Loth
Ani Manichaikul
Ingo Marenholz
Fernando Martinez
Melanie Matheson
Rasika Mathias
Kenji Matsumoto
Hamdi Mbarek
Wendy McArdle
Mads Melbye
Erik Melén
Deborah Meyers
Sven Michel
Hamida Mohamdi
Arthur Musk
Rachel Myers
Maartje Nieuwenhuis
Emiko Noguchi
George O'Connor
Ludmila Ogorodova
Cameron Palmer
Aarno Palotie
Julie Park
Craig Pennell
Göran Pershagen
Alexey Polonikov
Dirkje Postma
Nicole Probst-Hensch
Valery Puzyrev
Benjamin Raby
Olli Raitakari
Adaikalavan Ramasamy
Stephen Rich
Colin Robertson
Isabelle Romieu
Muhammad Salam
Veikko Salomaa
Vivi Schlünssen
Robert Scott
Polina Selivanova
Torben Sigsgaard
Angela Simpson
Valérie Siroux
Lewis Smith
Maria Solodilova
Marie Standl
Kari Stefansson
David Strachan
Bruno Stricker
Atsushi Takahashi
Philip Thompson
Gudmar Thorleifsson
Unnur Thorsteinsdottir
Carla Tiesler
Dara Torgerson
Tatsuhiko Tsunoda
André Uitterlinden
Ralf van der Valk
Amaury Vaysse
Sailaja Vedantam
Andrea von Berg
Erika von Mutius
Judith Vonk
Johannes Waage
Nick Wareham
Scott Weiss
Wendy White
Magnus Wickman
Elisabeth Widén
Gonneke Willemsen
L Keoki Williams
Inge Wouters
James Yang
Jing Zhao
Miriam Moffatt
Carole Ober
Dan Nicolae
Keywords
Humans
Genetic Predisposition to Disease
Phenotype
Alleles
Genome-Wide Association Study
Enhancer Elements, Genetic
Epigenesis, Genetic
Promoter Regions, Genetic
Genetic Loci
Asthma
Leukocytes
Risk
Histone Code
Rhinitis, Allergic, Seasonal
Abstract

We examined common variation in asthma risk by conducting a meta-analysis of worldwide asthma genome-wide association studies (23,948 asthma cases, 118,538 controls) of individuals from ethnically diverse populations. We identified five new asthma loci, found two new associations at two known asthma loci, established asthma associations at two loci previously implicated in the comorbidity of asthma plus hay fever, and confirmed nine known loci. Investigation of pleiotropy showed large overlaps in genetic variants with autoimmune and inflammatory diseases. The enrichment in enhancer marks at asthma risk loci, especially in immune cells, suggested a major role of these loci in the regulation of immunologically related mechanisms.
Year of Publication
2018
Journal
Nat Genet
Volume
50
Issue
1
Pages
42-53
Date Published
2018 01
ISSN
1546-1718
DOI
10.1038/s41588-017-0014-7
PubMed ID
29273806
PubMed Central ID
PMC5901974
Links
Grant list
G0401540 / MRC_ / Medical Research Council / United Kingdom
MR/K002449/2 / MRC_ / Medical Research Council / United Kingdom
R01 HL077612 / HL / NHLBI NIH HHS / United States
MR/K002449/1 / MRC_ / Medical Research Council / United Kingdom
G0601361 / MRC_ / Medical Research Council / United Kingdom
MC_UU_12015/1 / MRC_ / Medical Research Council / United Kingdom
RC2 HL101651 / HL / NHLBI NIH HHS / United States
648916 / ERC_ / European Research Council / International
G0902125 / MRC_ / Medical Research Council / United Kingdom
P01 CA196569 / CA / NCI NIH HHS / United States
P30 ES006694 / ES / NIEHS NIH HHS / United States
U01 HL130114 / HL / NHLBI NIH HHS / United States
G9815508 / MRC_ / Medical Research Council / United Kingdom
P30 ES009089 / ES / NIEHS NIH HHS / United States

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