Title

Multiethnic meta-analysis identifies ancestry-specific and cross-ancestry loci for pulmonary function.

Authors

Annah B Wyss
Tamar Sofer
Mi Kyeong Lee
Natalie Terzikhan
Jennifer N Nguyen
Lies Lahousse
Jeanne C Latourelle
Albert Vernon Smith
Traci M Bartz
Mary F Feitosa
Wei Gao
Tarunveer S Ahluwalia
Wenbo Tang
Christopher Oldmeadow
Qing Duan
Kim de Jong
Mary K Wojczynski
Xin-Qun Wang
Raymond Noordam
Fernando Pires Hartwig
Victoria E Jackson
Tianyuan Wang
Ma'en Obeidat
Brian D Hobbs
Tianxiao Huan
Hongsheng Gui, Henry Ford Health SystemFollow
Margaret M Parker
Donglei Hu
Lauren S Mogil
Gleb Kichaev
Jianping Jin
Mariaelisa Graff
Tamara B Harris
Ravi Kalhan
Susan R Heckbert
Lavinia Paternoster
Kristin M Burkart
Yongmei Liu
Elizabeth G Holliday
James G Wilson
Judith M Vonk
Jason L Sanders
R Graham Barr
Renée de Mutsert
Ana Maria Baptista Menezes
Hieab H H Adams
Maarten van den Berge
Roby Joehanes
Albert M. Levin, Henry Ford Health SystemFollow
Jennifer Liberto
Lenore J Launer
Alanna C Morrison
Colleen M Sitlani
Juan C Celedón
Stephen B Kritchevsky
Rodney J Scott
Kaare Christensen
Jerome I Rotter
Tobias N Bonten
Fernando César Wehrmeister
Yohan Bossé
Shujie Xiao, Henry Ford Health SystemFollow
Sam Oh
Nora Franceschini
Jennifer A Brody
Robert C Kaplan
Kurt Lohman
Mark McEvoy
Michael A Province
Frits R Rosendaal
Kent D Taylor
David C Nickle
Keoki L. Williams, Henry Ford Health SystemFollow
Esteban G Burchard
Heather E Wheeler
Don D Sin
Vilmundur Gudnason
Kari E North
Myriam Fornage
Bruce M Psaty
Richard H Myers
George O'Connor
Torben Hansen
Cathy C Laurie
Patricia A Cassano
Joohon Sung
Woo Jin Kim
John R Attia
Leslie Lange
H Marike Boezen
Bharat Thyagarajan
Stephen S Rich
Dennis O Mook-Kanamori
Bernardo Lessa Horta
André G Uitterlinden
Hae Kyung Im
Michael H Cho
Guy G Brusselle
Sina A Gharib
Josée Dupuis
Ani Manichaikul
Stephanie J London

Document Type

Article

Publication Date

7-30-2018

Publication Title

Nat Commun

Abstract

Nearly 100 loci have been identified for pulmonary function, almost exclusively in studies of European ancestry populations. We extend previous research by meta-analyzing genome-wide association studies of 1000 Genomes imputed variants in relation to pulmonary function in a multiethnic population of 90,715 individuals of European (N = 60,552), African (N = 8429), Asian (N = 9959), and Hispanic/Latino (N = 11,775) ethnicities. We identify over 50 additional loci at genome-wide significance in ancestry-specific or multiethnic meta-analyses. Using recent fine-mapping methods incorporating functional annotation, gene expression, and differences in linkage disequilibrium between ethnicities, we further shed light on potential causal variants and genes at known and newly identified loci. Several of the novel genes encode proteins with predicted or established drug targets, including KCNK2 and CDK12. Our study highlights the utility of multiethnic and integrative genomics approaches to extend existing knowledge of the genetics of lung function and clinical relevance of implicated loci.

Medical Subject Headings

African Continental Ancestry Group; Asian Americans; European Continental Ancestry Group; Female; Forced Expiratory Volume; Genetic Predisposition to Disease; Genome-Wide Association Study; Genomics; Hispanic Americans; Humans; Linkage Disequilibrium; Lung; Lung Diseases; Male; Polymorphism, Single Nucleotide; Pulmonary Disease, Chronic Obstructive; Quantitative Trait Loci; Regression Analysis; Sample Size; Smoking; Vital Capacity

PubMed ID

30061609

Volume

9

Issue

1

First Page

2976

Last Page

2976

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