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

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 & 82 others Victoria E. Jackson, Tianyuan Wang, Ma’en Obeidat, Brian D. Hobbs, Tianxiao Huan, Hongsheng Gui, 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, 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, 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, L. Keoki Williams, 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

Research output: Contribution to journal › Article

6 Citations (Scopus)

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 languageEnglish (US)
Article number2976
JournalNature Communications
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2018

Fingerprint

pulmonary functions
loci
Meta-Analysis
genome
Genes
Hispanic Americans
Lung
Genome
genes
Genome-Wide Association Study
Linkage Disequilibrium
Genomics
annotations
Population
gene expression
linkages
lungs
Gene Expression
drugs
Gene expression

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Wyss, A. B., Sofer, T., Lee, M. K., Terzikhan, N., Nguyen, J. N., Lahousse, L., ... London, S. J. (2018). Multiethnic meta-analysis identifies ancestry-specific and cross-ancestry loci for pulmonary function. Nature Communications, 9(1), [2976]. https://doi.org/10.1038/s41467-018-05369-0

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

Wyss, AB, Sofer, T, Lee, MK, Terzikhan, N, Nguyen, JN, Lahousse, L, Latourelle, JC, Smith, AV, Bartz, TM, Feitosa, MF, Gao, W, Ahluwalia, TS, Tang, W, Oldmeadow, C, Duan, Q, de Jong, K, Wojczynski, MK, Wang, XQ, Noordam, R, Hartwig, FP, Jackson, VE, Wang, T, Obeidat, M, Hobbs, BD, Huan, T, Gui, H, Parker, MM, Hu, D, Mogil, LS, Kichaev, G, Jin, J, Graff, M, Harris, TB, Kalhan, R, Heckbert, SR, Paternoster, L, Burkart, KM, Liu, Y, Holliday, EG, Wilson, JG, Vonk, JM, Sanders, JL, Barr, RG, de Mutsert, R, Menezes, AMB, Adams, HHH, van den Berge, M, Joehanes, R, Levin, AM, Liberto, J, Launer, LJ, Morrison, AC, Sitlani, CM, Celedón, JC, Kritchevsky, SB, Scott, RJ, Christensen, K, Rotter, JI, Bonten, TN, Wehrmeister, FC, Bossé, Y, Xiao, S, Oh, S, Franceschini, N, Brody, JA, Kaplan, RC, Lohman, K, McEvoy, M, Province, MA, Rosendaal, FR, Taylor, KD, Nickle, DC, Williams, LK, Burchard, EG, Wheeler, HE, Sin, DD, Gudnason, V, North, KE, Fornage, M, Psaty, BM, Myers, RH, O’Connor, G, Hansen, T, Laurie, CC, Cassano, PA, Sung, J, Kim, WJ, Attia, JR, Lange, L, Boezen, HM, Thyagarajan, B, Rich, SS, Mook-Kanamori, DO, Horta, BL, Uitterlinden, AG, Im, HK, Cho, MH, Brusselle, GG, Gharib, SA, Dupuis, J, Manichaikul, A & London, SJ 2018, 'Multiethnic meta-analysis identifies ancestry-specific and cross-ancestry loci for pulmonary function', Nature Communications, vol. 9, no. 1, 2976. https://doi.org/10.1038/s41467-018-05369-0
Wyss AB, Sofer T, Lee MK, Terzikhan N, Nguyen JN, Lahousse L et al. Multiethnic meta-analysis identifies ancestry-specific and cross-ancestry loci for pulmonary function. Nature Communications. 2018 Dec 1;9(1). 2976. https://doi.org/10.1038/s41467-018-05369-0
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. / Multiethnic meta-analysis identifies ancestry-specific and cross-ancestry loci for pulmonary function. In: Nature Communications. 2018 ; Vol. 9, No. 1.
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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.",
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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.

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U2 - 10.1038/s41467-018-05369-0

DO - 10.1038/s41467-018-05369-0

M3 - Article

VL - 9

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 2976

ER -

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