Multiethnic Meta-Analysis Identifies Ancestry-Specific and Cross-Ancestry Loci for Pulmonary Function

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Wyss, Annah B.; Sofer, Tamar; Lee, Mi Kyeong; Terzikhan, Natalie; Nguyen, Jennifer N.; Lahousse, Lies; Latourelle, Jeanne C.; Smith, Albert V.; Bartz, Traci M.; & Feitosa, Mary F., et al. (2018). Multiethnic Meta-Analysis Identifies Ancestry-Specific and Cross-Ancestry Loci for Pulmonary Function. Nature Communications, 9, 2976. PMCID: PMC6065313

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.

URL

http://dx.doi.org/10.1038/s41467-018-05369-0

Reference Type

Journal Article

Year Published

2018

Journal Title

Nature Communications

Author(s)

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

PMCID

PMC6065313

ORCiD

Graff - 0000-0001-6380-1735