TY - JOUR
T1 - Multiethnic meta-analysis identifies ancestry-specific and cross-ancestry loci for pulmonary function
AU - Wyss, Annah B.
AU - Sofer, Tamar
AU - Lee, Mi Kyeong
AU - Terzikhan, Natalie
AU - Nguyen, Jennifer N.
AU - Lahousse, Lies
AU - Latourelle, Jeanne C.
AU - Smith, Albert Vernon
AU - Bartz, Traci M.
AU - Feitosa, Mary F.
AU - Gao, Wei
AU - Ahluwalia, Tarunveer S.
AU - Tang, Wenbo
AU - Oldmeadow, Christopher
AU - Duan, Qing
AU - de Jong, Kim
AU - Wojczynski, Mary K.
AU - Wang, Xin Qun
AU - Noordam, Raymond
AU - Hartwig, Fernando Pires
AU - Jackson, Victoria E.
AU - Wang, Tianyuan
AU - Obeidat, Ma’en
AU - Hobbs, Brian D.
AU - Huan, Tianxiao
AU - Gui, Hongsheng
AU - Parker, Margaret M.
AU - Hu, Donglei
AU - Mogil, Lauren S.
AU - Kichaev, Gleb
AU - Jin, Jianping
AU - Graff, Mariaelisa
AU - Harris, Tamara B.
AU - Kalhan, Ravi
AU - Heckbert, Susan R.
AU - Paternoster, Lavinia
AU - Burkart, Kristin M.
AU - Liu, Yongmei
AU - Holliday, Elizabeth G.
AU - Wilson, James G.
AU - Vonk, Judith M.
AU - Sanders, Jason L.
AU - Barr, R. Graham
AU - de Mutsert, Renée
AU - Menezes, Ana Maria Baptista
AU - Adams, Hieab H.H.
AU - van den Berge, Maarten
AU - Joehanes, Roby
AU - Levin, Albert M.
AU - Liberto, Jennifer
PY - 2018/7/30
Y1 - 2018/7/30
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85050820503&partnerID=8YFLogxK
U2 - 10.1038/s41467-018-05369-0
DO - 10.1038/s41467-018-05369-0
M3 - Article (Academic Journal)
C2 - 30061609
AN - SCOPUS:85050820503
SN - 2041-1723
VL - 9
JO - Nature Communications
JF - Nature Communications
M1 - 2976
ER -
