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

被引：671

作者：

Torgerson, Dara G. ^{[1
]}

Ampleford, Elizabeth J. ^{[2
]}

Chiu, Grace Y. ^{[3
]}

Gauderman, W. James ^{[4
]}

Gignoux, Christopher R. ^{[5
]}

Graves, Penelope E. ^{[6
,7
]}

Himes, Blanca E. ^{[8
,9
]}

Levin, Albert M. ^{[10
]}

Mathias, Rasika A. ^{[11
]}

Hancock, Dana B. ^{[12
]}

Baurley, James W. ^{[4
]}

Eng, Celeste ^{[5
]}

Stern, Debra A. ^{[6
,7
]}

Celedon, Juan C. ^{[13
]}

Rafaels, Nicholas ^{[11
]}

Capurso, Daniel ^{[1
]}

Conti, David V. ^{[4
]}

Roth, Lindsey A. ^{[5
]}

Soto-Quiros, Manuel ^{[14
]}

Togias, Alkis ^{[11
]}

Li, Xingnan ^{[2
]}

Myers, Rachel A. ^{[1
]}

Romieu, Isabelle ^{[15
]}

Van Den Berg, David J. ^{[4
]}

Hu, Donglei ^{[5
]}

Hansel, Nadia N. ^{[11
,16
]}

Hernandez, Ryan D. ^{[17
]}

Israel, Elliott ^{[8
,9
]}

Salam, Muhammad T. ^{[4
]}

Galanter, Joshua ^{[5
]}

Avila, Pedro C. ^{[18
]}

Avila, Lydiana ^{[14
]}

Rodriquez-Santana, Jose R. ^{[19
]}

Chapela, Rocio ^{[20
]}

Rodriguez-Cintron, William ^{[21
]}

Diette, Gregory B. ^{[11
,16
]}

Adkinson, N. Franklin ^{[11
]}

Abel, Rebekah A. ^{[1
]}

Ross, Kevin D. ^{[1
]}

Shi, Min ^{[12
]}

Faruque, Mezbah U. ^{[22
]}

Dunston, Georgia M. ^{[23
]}

Watson, Harold R. ^{[24
,25
]}

Mantese, Vito J. ^{[11
]}

Ezurum, Serpil C. ^{[26
,27
]}

Liang, Liming ^{[28
,29
]}

Ruczinski, Ingo ^{[30
]}

Ford, Jean G. ^{[16
]}

Huntsman, Scott ^{[5
]}

Chung, Kian Fan ^{[31
]}

机构：

[1] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA

[2] Wake Forest Univ, Bowman Gray Sch Med, Ctr Genom, Winston Salem, NC USA

[3] Westat Corp, Res Triangle Pk, NC USA

[4] Univ So Calif, Dept Prevent Med, Los Angeles, CA 90089 USA

[5] Univ Calif San Francisco, Dept Med, San Francisco, CA USA

[6] Univ Arizona, Arizona Resp Ctr, Tucson, AZ USA

[7] Univ Arizona, Inst BIO5, Tucson, AZ USA

[8] Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA

[9] Harvard Univ, Sch Med, Boston, MA USA

[10] Henry Ford Hlth Syst, Dept Publ Hlth Sci, Detroit, MI USA

[11] Johns Hopkins Univ, Dept Med, Baltimore, MD USA

[12] Natl Inst Environm Hlth Sci, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC USA

[13] Univ Pittsburgh, Div Pediat Pulmonol, Pittsburgh, PA USA

[14] Hosp Nacl Ninos Dr Carlos Saenz Herrera, San Jose, Costa Rica

[15] Inst Nacl Salud Publ, Mexico City, DF, Mexico

[16] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA

[17] Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, San Francisco, CA 94143 USA

[18] Northwestern Univ, Dept Med, Chicago, IL 60611 USA

[19] Ctr Neumol Pediat, San Juan, PR USA

[20] Inst Nacl Enfermedades Resp, Mexico City, DF, Mexico

[21] Vet Affairs Med Ctr, San Juan, PR USA

[22] Howard Univ, Coll Med, Dept Community & Family Med, Washington, DC USA

[23] Howard Univ, Dept Microbiol, Washington, DC 20059 USA

[24] Univ W Indies, Fac Med Sci, St Michael, Barbados

[25] Queen Elizabeth Hosp, St Michael, Barbados

[26] Cleveland Clin, Lerner Res Inst, Cleveland, OH 44106 USA

[27] Cleveland Clin, Resp Inst, Cleveland, OH 44106 USA

[28] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA

[29] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA

[30] Johns Hopkins Univ, Dept Biostat, Baltimore, MD 21205 USA

[31] Imperial Coll Sch Med, London, England

[32] Univ Texas Med Branch, Dept Internal Med, Galveston, TX USA

[33] Washington Univ, Dept Med, St Louis, MO USA

[34] Hosp Infantil Mexico Dr Federico Gomez, Mexico City, DF, Mexico

[35] Univ Freiburg, Dept Pediat, D-7800 Freiburg, Germany

[36] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA

[37] Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Madison, WI USA

[38] Univ Wisconsin, Dept Pediat, Sch Med & Publ Hlth, Madison, WI USA

[39] Henry Ford Hlth Syst, Ctr Hlth Serv Res, Dept Internal Med, Detroit, MI USA

[40] Univ Chicago, Dept Med, Chicago, IL 60637 USA

[41] Univ Chicago, Dept Stat, Chicago, IL 60637 USA

来源：

NATURE GENETICS | 2011年 / 43卷 / 09期

关键词：

ORMDL3; EXPRESSION; CHILDHOOD ASTHMA; VARIANTS; 17Q21; SUSCEPTIBILITY; SEQUENCE; CHILDREN; ONSET; GENE;

D O I：

10.1038/ng.888

中图分类号：

Q3 [遗传学];

学科分类号：

071007 [遗传学];

摘要：

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 x 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.

引用

页码：887 / U103

页数：7

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