Further replication studies of the EVE Consortium meta-analysis identifies 2 asthma risk loci in European Americans

被引：23

作者：

Myers, Rachel A. ^{[1
]}

Himes, Blanca E. ^{[2
]}

Gignoux, Christopher R. ^{[3
]}

Yang, James J. ^{[4
]}

Gauderman, W. James ^{[5
]}

Rebordosa, Cristina ^{[6
,7
]}

Xie, Jianming ^{[1
,8
]}

Torgerson, Dara G. ^{[3
]}

Levin, Albert M. ^{[4
]}

Baurley, James ^{[5
]}

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

Mathias, Rasika A. ^{[9
]}

Romieu, Isabelle ^{[10
,11
]}

Roth, Lindsey A. ^{[3
]}

Conti, David ^{[5
]}

Avila, Lydiana ^{[12
]}

Eng, Celeste ^{[3
]}

Vora, Hita ^{[5
]}

LeNoir, Michael A. ^{[13
]}

Soto-Quiros, Manuel ^{[12
]}

Liu, Jinghua ^{[5
]}

Celedon, Juan C. ^{[14
]}

Farber, Harold J. ^{[15
]}

Kumar, Rajesh ^{[16
]}

Avila, Pedro C. ^{[17
]}

Meade, Kelley ^{[18
]}

Serebrisky, Denise ^{[19
,20
]}

Thyne, Shannon ^{[21
]}

Rodriguez-Cintron, William ^{[22
]}

Rodriguez-Santana, Jose R. ^{[23
]}

Borrell, Luisa N. ^{[24
]}

Lemanske, Robert F., Jr. ^{[25
]}

Bleecker, Eugene R. ^{[26
]}

Meyers, Deborah A. ^{[27
]}

London, Stephanie J. ^{[27
]}

Barnes, Kathleen C. ^{[9
]}

Raby, Benjamin A. ^{[2
]}

Martinez, Fernando D. ^{[6
,7
]}

Gilliland, Frank D. ^{[5
]}

Williams, L. Keoki ^{[28
]}

Burchard, Esteban G. ^{[3
,29
]}

Weiss, Scott T. ^{[2
]}

Nicolae, Dan L. ^{[1
,30
,31
]}

Ober, Carole ^{[1
]}

机构：

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

[2] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Channing Div Network Med, Boston, MA 02115 USA

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

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

[5] Univ So Calif, Dept Preventat Med, Los Angeles, CA USA

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

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

[8] Southeast Univ, Sch Biol Sci & Med Engn, Nanjing, Jiangsu, Peoples R China

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

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

[11] Int Agcy Res Canc, F-69372 Lyon, France

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

[13] Bay Area Pediat, Oakland, CA USA

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

[15] Baylor Coll Med, Dept Pediat, Sect Pulmonol, Houston, TX 77030 USA

[16] Ann & Robert H Lurie Childrens Hosp Chicago, Div Allergy & Immunol, Chicago, IL USA

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

[18] Childrens Hosp Oakland, Oakland, CA USA

[19] Albert Einstein Coll Med, Jacobi Med Ctr, Bronx, NY 10467 USA

[20] Albert Einstein Coll Med, Dept Pediat, Bronx, NY 10467 USA

[21] Univ Calif San Francisco, Dept Pediat, San Francisco, CA USA

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

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

[24] CUNY Herbert H Lehman Coll, Dept Hlth Sci, New York, NY USA

[25] Univ Wisconsin, Dept Pediat, Madison, WI USA

[26] Wake Forest Sch Med, Ctr Human Genom, Winston Salem, NC USA

[27] NIEHS, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA

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

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

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

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

来源：

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY | 2012年 / 130卷 / 06期

基金：

美国国家卫生研究院;

关键词：

Asthma; genetic risk factors; meta-analysis; KLK3; GENOME-WIDE ASSOCIATION; PROSTATE-SPECIFIC ANTIGEN; SUSCEPTIBILITY LOCI; INNATE IMMUNITY; VARIANTS; GENETICS; SCREEN; SEQUENCE;

D O I：

10.1016/j.jaci.2012.07.054

中图分类号：

R392 [医学免疫学];

学科分类号：

100102 ;

摘要：

Background: Genome-wide association studies of asthma have implicated many genetic risk factors, with well-replicated associations at approximately 10 loci that account for only a small proportion of the genetic risk. Objectives: We aimed to identify additional asthma risk loci by performing an extensive replication study of the results from the EVE Consortium meta-analysis. Methods: We selected 3186 single nucleotide polymorphisms for replication based on the P values from the EVE Consortium meta-analysis. These single nucleotide polymorphisms were genotyped in ethnically diverse replication samples from 9 different studies, totaling 7202 cases, 6426 controls, and 507 case-parent trios. Association analyses were conducted within each participating study, and the resulting test statistics were combined in a meta-analysis. Results: Two novel associations were replicated in European Americans: rs1061477 in the KLK3 gene on chromosome 19 (combined odds ratio = 1.18; 95% CI, 1.10-1.25) and rs9570077 (combined odds ratio =1.20; 95% CI, 1.12-1.29) on chromosome 13q21. We could not replicate any additional associations in the African Americans or Latinos. Conclusions: This extended replication study identified 2 additional asthma risk loci in populations of European descent. The absence of additional loci for African Americans and Latinos highlights the difficulty in replicating associations in admixed populations. (J Allergy Clin Immunol 2012;130:1294-301.)

引用

页码：1294 / 1301

页数：8

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