Meta-analysis of genome-wide association studies of asthma in ethnically diverse North American populations

Dara G. Torgerson; Elizabeth J. Ampleford; Grace Y. Chiu; W. James Gauderman; Christopher R. Gignoux; Penelope E. Graves; Blanca E. Himes; Albert M. Levin; Rasika A. Mathias; Dana B. Hancock; James W. Baurley; Celeste Eng; Debra A. Stern; Juan C. Celedón; Nicholas Rafaels; Daniel Capurso; David V. Conti; Lindsey A. Roth; Manuel Soto-Quiros; Alkis Togias; Xingnan Li; Rachel A. Myers; Isabelle Romieu; David J.Van Den Berg; Donglei Hu; Nadia N. Hansel; Ryan D. Hernandez; Elliott Israel; Muhammad T. Salam; Joshua Galanter; Pedro C. Avila; Lydiana Avila; Jose R. Rodriquez-Santana; Rocio Chapela; William Rodriguez-Cintron; Gregory B. Diette; N. Franklin Adkinson; Rebekah A. Abel; Kevin D. Ross; Min Shi; Mezbah U. Faruque; Georgia M. Dunston; Harold R. Watson; Vito J. Mantese; Serpil C. Ezurum; Liming Liang; Ingo Ruczinski; Jean G. Ford; Scott Huntsman; Kian Fan Chung; Hita Vora; Xia Li; William J. Calhoun; Mario Castro; Juan J. Sienra-Monge; Blanca Del Rio-Navarro; Klaus A. Deichmann; Andrea Heinzmann; Sally E. Wenzel; William W. Busse; James E. Gern; Robert F. Lemanske; Terri H. Beaty; Eugene R. Bleecker; Benjamin A. Raby; Deborah A. Meyers; Stephanie J. London; Frank D. Gilliland; Esteban G. Burchard; Fernando D. Martinez; Scott T. Weiss; L. Keoki Williams; Kathleen C. Barnes; Carole Ober; Dan L. Nicolae

doi:10.1038/ng.888

Meta-analysis of genome-wide association studies of asthma in ethnically diverse North American populations

Dara G. Torgerson, Elizabeth J. Ampleford, Grace Y. Chiu, W. James Gauderman, Christopher R. Gignoux, Penelope E. Graves, Blanca E. Himes, Albert M. Levin, Rasika A. Mathias, Dana B. Hancock, James W. Baurley, Celeste Eng, Debra A. Stern, Juan C. Celedón, Nicholas Rafaels, Daniel Capurso, David V. Conti, Lindsey A. Roth, Manuel Soto-Quiros, Alkis TogiasXingnan Li, Rachel A. Myers, Isabelle Romieu, David J.Van Den Berg, Donglei Hu, Nadia N. Hansel, Ryan D. Hernandez, Elliott Israel, Muhammad T. Salam, Joshua Galanter, Pedro C. Avila, Lydiana Avila, Jose R. Rodriquez-Santana, Rocio Chapela, William Rodriguez-Cintron, Gregory B. Diette, N. Franklin Adkinson, Rebekah A. Abel, Kevin D. Ross, Min Shi, Mezbah U. Faruque, Georgia M. Dunston, Harold R. Watson, Vito J. Mantese, Serpil C. Ezurum, Liming Liang, Ingo Ruczinski, Jean G. Ford, Scott Huntsman, Kian Fan Chung, Hita Vora, Xia Li, William J. Calhoun, Mario Castro, Juan J. Sienra-Monge, Blanca Del Rio-Navarro, Klaus A. Deichmann, Andrea Heinzmann, Sally E. Wenzel, William W. Busse, James E. Gern, Robert F. Lemanske, Terri H. Beaty, Eugene R. Bleecker, Benjamin A. Raby, Deborah A. Meyers, Stephanie J. London, Frank D. Gilliland, Esteban G. Burchard, Fernando D. Martinez, Scott T. Weiss, L. Keoki Williams, Kathleen C. Barnes, Carole Ober, Dan L. Nicolae

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Abstract

Asthma is a common disease with a complex risk architecture including both genetic and environmental factors. We performed a meta-analysis of North American genome-wide association studies of asthma in 5,416 individuals with asthma (cases) including individuals of European American, African American or African Caribbean, and Latino ancestry, with replication in an additional 12,649 individuals from the same ethnic groups. We identified five susceptibility loci. Four were at previously reported loci on 17q21, near IL1RL1, TSLP and IL33, but we report for the first time, to our knowledge, that these loci are associated with asthma risk in three ethnic groups. In addition, we identified a new asthma susceptibility locus at PYHIN1, with the association being specific to individuals of African descent (P = 3.9 × 10^-9). These results suggest that some asthma susceptibility loci are robust to differences in ancestry when sufficiently large samples sizes are investigated, and that ancestry-specific associations also contribute to the complex genetic architecture of asthma.

Original language	English (US)
Pages (from-to)	887-892
Number of pages	6
Journal	Nature genetics
Volume	43
Issue number	9
DOIs	https://doi.org/10.1038/ng.888
State	Published - Sep 2011

ASJC Scopus subject areas

Genetics

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10.1038/ng.888

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Torgerson, D. G., Ampleford, E. J., Chiu, G. Y., Gauderman, W. J., Gignoux, C. R., Graves, P. E., Himes, B. E., Levin, A. M., Mathias, R. A., Hancock, D. B., Baurley, J. W., Eng, C., Stern, D. A., Celedón, J. C., Rafaels, N., Capurso, D., Conti, D. V., Roth, L. A., Soto-Quiros, M., ... Nicolae, D. L. (2011). Meta-analysis of genome-wide association studies of asthma in ethnically diverse North American populations. Nature genetics, 43(9), 887-892. https://doi.org/10.1038/ng.888

Torgerson, DG, Ampleford, EJ, Chiu, GY, Gauderman, WJ, Gignoux, CR, Graves, PE, Himes, BE, Levin, AM, Mathias, RA, Hancock, DB, Baurley, JW, Eng, C, Stern, DA, Celedón, JC, Rafaels, N, Capurso, D, Conti, DV, Roth, LA, Soto-Quiros, M, Togias, A, Li, X, Myers, RA, Romieu, I, Berg, DJVD, Hu, D, Hansel, NN, Hernandez, RD, Israel, E, Salam, MT, Galanter, J, Avila, PC, Avila, L, Rodriquez-Santana, JR, Chapela, R, Rodriguez-Cintron, W, Diette, GB, Adkinson, NF, Abel, RA, Ross, KD, Shi, M, Faruque, MU, Dunston, GM, Watson, HR, Mantese, VJ, Ezurum, SC, Liang, L, Ruczinski, I, Ford, JG, Huntsman, S, Chung, KF, Vora, H, Li, X, Calhoun, WJ, Castro, M, Sienra-Monge, JJ, Del Rio-Navarro, B, Deichmann, KA, Heinzmann, A, Wenzel, SE, Busse, WW, Gern, JE, Lemanske, RF, Beaty, TH, Bleecker, ER, Raby, BA, Meyers, DA, London, SJ, Gilliland, FD, Burchard, EG, Martinez, FD, Weiss, ST, Williams, LK, Barnes, KC, Ober, C & Nicolae, DL 2011, 'Meta-analysis of genome-wide association studies of asthma in ethnically diverse North American populations', Nature genetics, vol. 43, no. 9, pp. 887-892. https://doi.org/10.1038/ng.888

@article{0f0ca8c039de462c83840360ef78bdc1,

title = "Meta-analysis of genome-wide association studies of asthma in ethnically diverse North American populations",

abstract = "Asthma is a common disease with a complex risk architecture including both genetic and environmental factors. We performed a meta-analysis of North American genome-wide association studies of asthma in 5,416 individuals with asthma (cases) including individuals of European American, African American or African Caribbean, and Latino ancestry, with replication in an additional 12,649 individuals from the same ethnic groups. We identified five susceptibility loci. Four were at previously reported loci on 17q21, near IL1RL1, TSLP and IL33, but we report for the first time, to our knowledge, that these loci are associated with asthma risk in three ethnic groups. In addition, we identified a new asthma susceptibility locus at PYHIN1, with the association being specific to individuals of African descent (P = 3.9 × 10-9). These results suggest that some asthma susceptibility loci are robust to differences in ancestry when sufficiently large samples sizes are investigated, and that ancestry-specific associations also contribute to the complex genetic architecture of asthma.",

author = "Torgerson, {Dara G.} and Ampleford, {Elizabeth J.} and Chiu, {Grace Y.} and Gauderman, {W. James} and Gignoux, {Christopher R.} and Graves, {Penelope E.} and Himes, {Blanca E.} and Levin, {Albert M.} and Mathias, {Rasika A.} and Hancock, {Dana B.} and Baurley, {James W.} and Celeste Eng and Stern, {Debra A.} and Celed{\'o}n, {Juan C.} and Nicholas Rafaels and Daniel Capurso and Conti, {David V.} and Roth, {Lindsey A.} and Manuel Soto-Quiros and Alkis Togias and Xingnan Li and Myers, {Rachel A.} and Isabelle Romieu and Berg, {David J.Van Den} and Donglei Hu and Hansel, {Nadia N.} and Hernandez, {Ryan D.} and Elliott Israel and Salam, {Muhammad T.} and Joshua Galanter and Avila, {Pedro C.} and Lydiana Avila and Rodriquez-Santana, {Jose R.} and Rocio Chapela and William Rodriguez-Cintron and Diette, {Gregory B.} and Adkinson, {N. Franklin} and Abel, {Rebekah A.} and Ross, {Kevin D.} and Min Shi and Faruque, {Mezbah U.} and Dunston, {Georgia M.} and Watson, {Harold R.} and Mantese, {Vito J.} and Ezurum, {Serpil C.} and Liming Liang and Ingo Ruczinski and Ford, {Jean G.} and Scott Huntsman and Chung, {Kian Fan} and Hita Vora and Xia Li and Calhoun, {William J.} and Mario Castro and Sienra-Monge, {Juan J.} and {Del Rio-Navarro}, Blanca and Deichmann, {Klaus A.} and Andrea Heinzmann and Wenzel, {Sally E.} and Busse, {William W.} and Gern, {James E.} and Lemanske, {Robert F.} and Beaty, {Terri H.} and Bleecker, {Eugene R.} and Raby, {Benjamin A.} and Meyers, {Deborah A.} and London, {Stephanie J.} and Gilliland, {Frank D.} and Burchard, {Esteban G.} and Martinez, {Fernando D.} and Weiss, {Scott T.} and Williams, {L. Keoki} and Barnes, {Kathleen C.} and Carole Ober and Nicolae, {Dan L.}",

note = "Funding Information: This work was supported by grants from the Office of the Director, NIH to C.O. and D.L.N. and the National Heart, Lung, and Blood Institute (HL101651 to C.O. and D.L.N.; HL087665 to D.L.N.; HL070831, HL072414 and HL049596 to C.O.; HL064307 and HL064313 to F.D.M.; HL075419, HL65899, HL083069, HL066289, HL087680, HL101543 and HL101651 to S.T.W.; HL079055 to L.K.W.; HL087699, HL49612, HL075417, HL04266 and HL072433 to K.C.B.; HL061768 and HL076647 to F.D.G.; HL087680 to W.J.G.; HL078885 and HL088133 to E.G.B.; HL87665 to D.A.M.; and HL69116, HL69130, HL69149, HL69155, HL69167, HL69170, HL69174 and HL69349 to D.A.M., E.R.B., W.W.B., W.J.C., M.C., K.F.C., S.C.E., E.I. and S.E.W.), the National Institutes of Allergy and Infectious Disease (AI070503 to C.O.; AI079139 and AI061774 to L.K.W.; AI50024, AI44840 and AI41040 to K.C.B.; and AI077439 to E.G.B.), the National Institute of Diabetes and Digestive and Kidney Diseases to L.K.W. (DK064695); the National Institutes of Environmental Health Sciences (ES09606, ES018176 and ES015903 to K.C.B.; ES007048, ES009581, R826708, RD831861 and ES011627 to F.D.G.; ES015794 to E.G.B.; and the Division of Intramural Research, Z01 ES049019, to S.J.L.); the National Center for Research Resources (RR03048 to K.C.B.), the Environmental Protection Agency (83213901 and R-826724 to K.C.B.), the American Asthma Foundation and the Fund for Henry Ford Hospital (to L.K.W.), Mary Beryl Patch Turnbull Scholar Program (to K.C.B.), the National Council of Science and Technology (Mexico) (26206-M to I. Ruczinski), the Centers for Disease Control, US (to I. Ruczinski), the Eudowood Foundation (to N.N.H.); and the Flight Attendant Medical Research Institute (FAMRI), Robert Wood Johnson Foundation (RWJF) Amos Medical Faculty Development Award, the American Asthma Foundation, and the Sandler Foundation (to E.G.B.). The authors gratefully acknowledge the contributions of H. Moreno-Macias, A. Barraza-Villarreal and M. Ramirez-Aguilar to the MCCAS; R. McConnell, D.C. Thomas, E. Avol, K. Berhane, J. Liu, E. Rappaport and C. Edlund to the CHS; L.N. Borrell, H. Farber, R. Kumar and D. Serebrisky to the GALA and GALA2 studies; S. Thyne to the GALA2 and SAGE studies; M. LeNoir, K. Meade and H. Geoff Watson to the SAGE study; and A.V. Grant, L. Gao, C. Vergara, Y.J. Tsai, P. Gao, M.C. Liu, P. Breysse, M.B. Bracken, J. Hoh, E.W. Pugh, A.F. Scott, G. Abecasis, T. Murray, T. Hand, M. Yang, M. Campbell, C. Foster, J.B. Hetmanski, R. Ashworth, C.M. Ongaco, K.N. Hetrick and K.F. Doheny to the GRAAD study. The authors also acknowledge the support from J. Kiley, S. Banks-Schlegel and W. Gan at the National Heart, Lung, and Blood Institute and all the subjects and families that participated in these studies.",

year = "2011",

month = sep,

doi = "10.1038/ng.888",

language = "English (US)",

volume = "43",

pages = "887--892",

journal = "Nature genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "9",

}

TY - JOUR

T1 - Meta-analysis of genome-wide association studies of asthma in ethnically diverse North American populations

AU - Torgerson, Dara G.

AU - Ampleford, Elizabeth J.

AU - Chiu, Grace Y.

AU - Gauderman, W. James

AU - Gignoux, Christopher R.

AU - Graves, Penelope E.

AU - Himes, Blanca E.

AU - Levin, Albert M.

AU - Mathias, Rasika A.

AU - Hancock, Dana B.

AU - Baurley, James W.

AU - Eng, Celeste

AU - Stern, Debra A.

AU - Celedón, Juan C.

AU - Rafaels, Nicholas

AU - Capurso, Daniel

AU - Conti, David V.

AU - Roth, Lindsey A.

AU - Soto-Quiros, Manuel

AU - Togias, Alkis

AU - Li, Xingnan

AU - Myers, Rachel A.

AU - Romieu, Isabelle

AU - Berg, David J.Van Den

AU - Hu, Donglei

AU - Hansel, Nadia N.

AU - Hernandez, Ryan D.

AU - Israel, Elliott

AU - Salam, Muhammad T.

AU - Galanter, Joshua

AU - Avila, Pedro C.

AU - Avila, Lydiana

AU - Rodriquez-Santana, Jose R.

AU - Chapela, Rocio

AU - Rodriguez-Cintron, William

AU - Diette, Gregory B.

AU - Adkinson, N. Franklin

AU - Abel, Rebekah A.

AU - Ross, Kevin D.

AU - Shi, Min

AU - Faruque, Mezbah U.

AU - Dunston, Georgia M.

AU - Watson, Harold R.

AU - Mantese, Vito J.

AU - Ezurum, Serpil C.

AU - Liang, Liming

AU - Ruczinski, Ingo

AU - Ford, Jean G.

AU - Huntsman, Scott

AU - Chung, Kian Fan

AU - Vora, Hita

AU - Li, Xia

AU - Calhoun, William J.

AU - Castro, Mario

AU - Sienra-Monge, Juan J.

AU - Del Rio-Navarro, Blanca

AU - Deichmann, Klaus A.

AU - Heinzmann, Andrea

AU - Wenzel, Sally E.

AU - Busse, William W.

AU - Gern, James E.

AU - Lemanske, Robert F.

AU - Beaty, Terri H.

AU - Bleecker, Eugene R.

AU - Raby, Benjamin A.

AU - Meyers, Deborah A.

AU - London, Stephanie J.

AU - Gilliland, Frank D.

AU - Burchard, Esteban G.

AU - Martinez, Fernando D.

AU - Weiss, Scott T.

AU - Williams, L. Keoki

AU - Barnes, Kathleen C.

AU - Ober, Carole

AU - Nicolae, Dan L.

N1 - Funding Information: This work was supported by grants from the Office of the Director, NIH to C.O. and D.L.N. and the National Heart, Lung, and Blood Institute (HL101651 to C.O. and D.L.N.; HL087665 to D.L.N.; HL070831, HL072414 and HL049596 to C.O.; HL064307 and HL064313 to F.D.M.; HL075419, HL65899, HL083069, HL066289, HL087680, HL101543 and HL101651 to S.T.W.; HL079055 to L.K.W.; HL087699, HL49612, HL075417, HL04266 and HL072433 to K.C.B.; HL061768 and HL076647 to F.D.G.; HL087680 to W.J.G.; HL078885 and HL088133 to E.G.B.; HL87665 to D.A.M.; and HL69116, HL69130, HL69149, HL69155, HL69167, HL69170, HL69174 and HL69349 to D.A.M., E.R.B., W.W.B., W.J.C., M.C., K.F.C., S.C.E., E.I. and S.E.W.), the National Institutes of Allergy and Infectious Disease (AI070503 to C.O.; AI079139 and AI061774 to L.K.W.; AI50024, AI44840 and AI41040 to K.C.B.; and AI077439 to E.G.B.), the National Institute of Diabetes and Digestive and Kidney Diseases to L.K.W. (DK064695); the National Institutes of Environmental Health Sciences (ES09606, ES018176 and ES015903 to K.C.B.; ES007048, ES009581, R826708, RD831861 and ES011627 to F.D.G.; ES015794 to E.G.B.; and the Division of Intramural Research, Z01 ES049019, to S.J.L.); the National Center for Research Resources (RR03048 to K.C.B.), the Environmental Protection Agency (83213901 and R-826724 to K.C.B.), the American Asthma Foundation and the Fund for Henry Ford Hospital (to L.K.W.), Mary Beryl Patch Turnbull Scholar Program (to K.C.B.), the National Council of Science and Technology (Mexico) (26206-M to I. Ruczinski), the Centers for Disease Control, US (to I. Ruczinski), the Eudowood Foundation (to N.N.H.); and the Flight Attendant Medical Research Institute (FAMRI), Robert Wood Johnson Foundation (RWJF) Amos Medical Faculty Development Award, the American Asthma Foundation, and the Sandler Foundation (to E.G.B.). The authors gratefully acknowledge the contributions of H. Moreno-Macias, A. Barraza-Villarreal and M. Ramirez-Aguilar to the MCCAS; R. McConnell, D.C. Thomas, E. Avol, K. Berhane, J. Liu, E. Rappaport and C. Edlund to the CHS; L.N. Borrell, H. Farber, R. Kumar and D. Serebrisky to the GALA and GALA2 studies; S. Thyne to the GALA2 and SAGE studies; M. LeNoir, K. Meade and H. Geoff Watson to the SAGE study; and A.V. Grant, L. Gao, C. Vergara, Y.J. Tsai, P. Gao, M.C. Liu, P. Breysse, M.B. Bracken, J. Hoh, E.W. Pugh, A.F. Scott, G. Abecasis, T. Murray, T. Hand, M. Yang, M. Campbell, C. Foster, J.B. Hetmanski, R. Ashworth, C.M. Ongaco, K.N. Hetrick and K.F. Doheny to the GRAAD study. The authors also acknowledge the support from J. Kiley, S. Banks-Schlegel and W. Gan at the National Heart, Lung, and Blood Institute and all the subjects and families that participated in these studies.

PY - 2011/9

Y1 - 2011/9

N2 - Asthma is a common disease with a complex risk architecture including both genetic and environmental factors. We performed a meta-analysis of North American genome-wide association studies of asthma in 5,416 individuals with asthma (cases) including individuals of European American, African American or African Caribbean, and Latino ancestry, with replication in an additional 12,649 individuals from the same ethnic groups. We identified five susceptibility loci. Four were at previously reported loci on 17q21, near IL1RL1, TSLP and IL33, but we report for the first time, to our knowledge, that these loci are associated with asthma risk in three ethnic groups. In addition, we identified a new asthma susceptibility locus at PYHIN1, with the association being specific to individuals of African descent (P = 3.9 × 10-9). These results suggest that some asthma susceptibility loci are robust to differences in ancestry when sufficiently large samples sizes are investigated, and that ancestry-specific associations also contribute to the complex genetic architecture of asthma.

AB - Asthma is a common disease with a complex risk architecture including both genetic and environmental factors. We performed a meta-analysis of North American genome-wide association studies of asthma in 5,416 individuals with asthma (cases) including individuals of European American, African American or African Caribbean, and Latino ancestry, with replication in an additional 12,649 individuals from the same ethnic groups. We identified five susceptibility loci. Four were at previously reported loci on 17q21, near IL1RL1, TSLP and IL33, but we report for the first time, to our knowledge, that these loci are associated with asthma risk in three ethnic groups. In addition, we identified a new asthma susceptibility locus at PYHIN1, with the association being specific to individuals of African descent (P = 3.9 × 10-9). These results suggest that some asthma susceptibility loci are robust to differences in ancestry when sufficiently large samples sizes are investigated, and that ancestry-specific associations also contribute to the complex genetic architecture of asthma.

UR - http://www.scopus.com/inward/record.url?scp=80052259316&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80052259316&partnerID=8YFLogxK

U2 - 10.1038/ng.888

DO - 10.1038/ng.888

M3 - Article

C2 - 21804549

AN - SCOPUS:80052259316

SN - 1061-4036

VL - 43

SP - 887

EP - 892

JO - Nature genetics

JF - Nature genetics

IS - 9

ER -

Meta-analysis of genome-wide association studies of asthma in ethnically diverse North American populations

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