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.
| Original language | English (US) |
|---|---|
| Article number | 2976 |
| Journal | Nature Communications |
| Volume | 9 |
| Issue number | 1 |
| DOIs | |
| State | Published - Dec 1 2018 |
Fingerprint
ASJC Scopus subject areas
- Chemistry(all)
- Biochemistry, Genetics and Molecular Biology(all)
- Physics and Astronomy(all)
Cite this
Multiethnic meta-analysis identifies ancestry-specific and cross-ancestry loci for pulmonary function. / Wyss, Annah B.; Sofer, Tamar; Lee, Mi Kyeong; Terzikhan, Natalie; Nguyen, Jennifer N.; Lahousse, Lies; Latourelle, Jeanne C.; Smith, Albert Vernon; 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, Renée; Menezes, Ana Maria Baptista; Adams, Hieab H.H.; van den Berge, Maarten; Joehanes, Roby; Levin, Albert M.; Liberto, Jennifer; Launer, Lenore J.; Morrison, Alanna C.; Sitlani, Colleen M.; Celedón, Juan C.; Kritchevsky, Stephen B.; Scott, Rodney J.; Christensen, Kaare; Rotter, Jerome I.; Bonten, Tobias N.; Wehrmeister, Fernando César; Bossé, Yohan; Xiao, Shujie; Oh, Sam; Franceschini, Nora; Brody, Jennifer A.; Kaplan, Robert C.; Lohman, Kurt; 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; 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; Boezen, H. Marike; Thyagarajan, Bharat; Rich, Stephen S.; Mook-Kanamori, Dennis O.; Horta, Bernardo Lessa; Uitterlinden, André G.; Im, Hae Kyung; Cho, Michael H.; Brusselle, Guy G.; Gharib, Sina A.; Dupuis, Josée; Manichaikul, Ani; London, Stephanie J.
In: Nature Communications, Vol. 9, No. 1, 2976, 01.12.2018.Research output: Contribution to journal › Article
}
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
AU - Launer, Lenore J.
AU - Morrison, Alanna C.
AU - Sitlani, Colleen M.
AU - Celedón, Juan C.
AU - Kritchevsky, Stephen B.
AU - Scott, Rodney J.
AU - Christensen, Kaare
AU - Rotter, Jerome I.
AU - Bonten, Tobias N.
AU - Wehrmeister, Fernando César
AU - Bossé, Yohan
AU - Xiao, Shujie
AU - Oh, Sam
AU - Franceschini, Nora
AU - Brody, Jennifer A.
AU - Kaplan, Robert C.
AU - Lohman, Kurt
AU - McEvoy, Mark
AU - Province, Michael A.
AU - Rosendaal, Frits R.
AU - Taylor, Kent D.
AU - Nickle, David C.
AU - Williams, L. Keoki
AU - Burchard, Esteban G.
AU - Wheeler, Heather E.
AU - Sin, Don D.
AU - Gudnason, Vilmundur
AU - North, Kari E.
AU - Fornage, Myriam
AU - Psaty, Bruce M.
AU - Myers, Richard H.
AU - O’Connor, George
AU - Hansen, Torben
AU - Laurie, Cathy C.
AU - Cassano, Patricia A.
AU - Sung, Joohon
AU - Kim, Woo Jin
AU - Attia, John R.
AU - Lange, Leslie
AU - Boezen, H. Marike
AU - Thyagarajan, Bharat
AU - Rich, Stephen S.
AU - Mook-Kanamori, Dennis O.
AU - Horta, Bernardo Lessa
AU - Uitterlinden, André G.
AU - Im, Hae Kyung
AU - Cho, Michael H.
AU - Brusselle, Guy G.
AU - Gharib, Sina A.
AU - Dupuis, Josée
AU - Manichaikul, Ani
AU - London, Stephanie J.
PY - 2018/12/1
Y1 - 2018/12/1
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
UR - http://www.scopus.com/inward/citedby.url?scp=85050820503&partnerID=8YFLogxK
U2 - 10.1038/s41467-018-05369-0
DO - 10.1038/s41467-018-05369-0
M3 - Article
C2 - 30061609
AN - SCOPUS:85050820503
VL - 9
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 2976
ER -