Genome-wide association study and admixture mapping identify different asthma-associated loci in Latinos: The Genes-environments & Admixture in Latino Americans study

被引：84

作者：

Galanter, Joshua M. ^{[1
,2
]}

Gignoux, Christopher R. ^{[2
]}

Torgerson, Dara G. ^{[1
]}

Roth, Lindsey A. ^{[1
]}

Eng, Celeste ^{[1
]}

Oh, Sam S. ^{[1
]}

Nguyen, Elizabeth A. ^{[3
]}

Drake, Katherine A. ^{[2
]}

Huntsman, Scott ^{[1
]}

Hu, Donglei ^{[1
]}

Sen, Saunak ^{[4
]}

Davis, Adam ^{[5
]}

Farber, Harold J. ^{[6
,7
]}

Avila, Pedro C. ^{[8
]}

Brigino-Buenaventura, Emerita ^{[9
]}

LeNoir, Michael A. ^{[10
]}

Meade, Kelley ^{[5
]}

Serebrisky, Denise ^{[11
]}

Borrell, Luisa N. ^{[12
]}

Rodriguez-Cintron, William ^{[13
]}

Estrada, Andres Moreno ^{[14
]}

Mendoza, Karla Sandoval ^{[14
]}

Winkler, Cheryl A. ^{[15
]}

Klitz, William ^{[16
]}

Romieu, Isabelle ^{[17
]}

London, Stephanie J. ^{[18
]}

Gilliland, Frank ^{[19
]}

Martinez, Fernando ^{[20
]}

Bustamante, Carlos ^{[14
]}

Williams, L. Keoki ^{[21
]}

Kumar, Rajesh ^{[22
]}

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

Burchard, Esteban G. ^{[1
,2
]}

机构：

[1] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA

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

[3] St Louis Univ, Sch Med, St Louis, MO 63103 USA

[4] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA

[5] Childrens Hosp & Res Ctr Oakland, Oakland, CA USA

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

[7] Texas Childrens Hosp, Houston, TX 77030 USA

[8] Northwestern Univ, Div Allergy Immunol, Feinberg Sch Med, Chicago, IL 60611 USA

[9] Kaiser Permanente Vallejo Med Ctr, Dept Allergy & Immunol, Vallejo, CA USA

[10] Bay Area Pediat, Oakland, CA USA

[11] Jacobi Med Ctr, Pediat Pulm Div, Bronx, NY USA

[12] CUNY Herbert H Lehman Coll, Dept Hlth Sci, Grad Program Publ Hlth, Bronx, NY 10468 USA

[13] Vet Caribbean Hlth Care Syst, San Juan, PR USA

[14] Stanford Univ, Dept Genet, Stanford, CA 94305 USA

[15] NIH, Frederick Natl Lab Canc Res, Frederick, MD USA

[16] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA

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

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

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

[20] Univ Arizona, Dept Pediat, Tucson, AZ 85721 USA

[21] Henry Ford Hlth Syst, Dept Internal Med, Detroit, MI USA

[22] Ann & Robert H Lurie Childrens Hosp Chicago, Chicago, IL USA

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

来源：

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY | 2014年 / 134卷 / 02期

基金：

美国国家卫生研究院;

关键词：

Asthma; Latinos; admixture mapping; genome-wide association study; local ancestry; 17q21; 6p21; AFRICAN-AMERICAN; UNITED-STATES; CANCER RISK; ANCESTRY; IDENTIFICATION; HERITABILITY; INDIVIDUALS; POPULATIONS; IMPUTATION; INFERENCE;

D O I：

10.1016/j.jaci.2013.08.055

中图分类号：

R392 [医学免疫学];

学科分类号：

100102 ;

摘要：

Background: Asthma is a complex disease with both genetic and environmental causes. Genome-wide association studies of asthma have mostly involved European populations, and replication of positive associations has been inconsistent. Objective: We sought to identify asthma-associated genes in a large Latino population with genome-wide association analysis and admixture mapping. Methods: Latino children with asthma (n = 1893) and healthy control subjects (n = 1881) were recruited from 5 sites in the United States: Puerto Rico, New York, Chicago, Houston, and the San Francisco Bay Area. Subjects were genotyped on an Affymetrix World Array IV chip. We performed genome-wide association and admixture mapping to identify asthma-associated loci. Results: We identified a significant association between ancestry and asthma at 6p21 (lowest P value: rs2523924, P < 5 x 10(-6)). This association replicates in a meta-analysis of the EVE Asthma Consortium (P = .01). Fine mapping of the region in this study and the EVE Asthma Consortium suggests an association between PSORS1C1 and asthma. We confirmed the strong allelic association between SNPs in the 17q21 region and asthma in Latinos (IKZF3, lowest P value: rs90792, odds ratio, 0.67; 95% CI, 0.61-0.75; P = 6 x 10(-13)) and replicated associations in several genes that had previously been associated with asthma in genome-wide association studies. Conclusions: Admixture mapping and genome-wide association are complementary techniques that provide evidence for multiple asthma-associated loci in Latinos. Admixture mapping identifies a novel locus on 6p21 that replicates in a meta-analysis of several Latino populations, whereas genome-wide association confirms the previously identified locus on 17q21.

引用

页码：295 / 305

页数：11

共 66 条

[1] Fast model-based estimation of ancestry in unrelated individuals [J].

Alexander, David H. ;

Novembre, John ;

Lange, Kenneth .

GENOME RESEARCH, 2009, 19 (09) :1655-1664

[2] Genome-Wide Scan Identifies TNIP1, PSORS1C1, and RHOB As Novel Risk Loci for Systemic Sclerosis [J].

Allanore, Yannick ;

Saad, Mohamad ;

Dieude, Philippe ;

Avouac, Jerome ;

Distler, Jorg H. W. ;

Amouyel, Philippe ;

Matucci-Cerinic, Marco ;

Riemekasten, Gabriella ;

Airo, Paolo ;

Melchers, Inga ;

Hachulla, Eric ;

Cusi, Daniele ;

Wichmann, H. -Erich ;

Wichmann, Erich ;

Wipff, Julien ;

Lambert, Jean-Charles ;

Hunzelmann, Nicolas ;

Tiev, Kiet ;

Caramaschi, Paola ;

Diot, Elisabeth ;

Kowal-Bielecka, Otylia ;

Valentini, Gabriele ;

Mouthon, Luc ;

Czirjak, Laszlo ;

Damjanov, Nemanja ;

Salvi, Erika ;

Conti, Costanza ;

Mueller, Martina ;

Mueller-Ladner, Ulf ;

Riccieri, Valeria ;

Ruiz, Barbara ;

Cracowski, Jean-Luc ;

Letenneur, Luc ;

Dupuy, Anne Marie ;

Meyer, Oliver ;

Kahan, Andre ;

Munnich, Arnold ;

Boileau, Catherine ;

Martinez, Maria .

PLOS GENETICS, 2011, 7 (07)

[3] A map of human genome variation from population-scale sequencing [J].

Altshuler, David ;

Durbin, Richard M. ;

Abecasis, Goncalo R. ;

Bentley, David R. ;

Chakravarti, Aravinda ;

Clark, Andrew G. ;

Collins, Francis S. ;

De la Vega, Francisco M. ;

Donnelly, Peter ;

Egholm, Michael ;

Flicek, Paul ;

Gabriel, Stacey B. ;

Gibbs, Richard A. ;

Knoppers, Bartha M. ;

Lander, Eric S. ;

Lehrach, Hans ;

Mardis, Elaine R. ;

McVean, Gil A. ;

Nickerson, DebbieA. ;

Peltonen, Leena ;

Schafer, Alan J. ;

Sherry, Stephen T. ;

Wang, Jun ;

Wilson, Richard K. ;

Gibbs, Richard A. ;

Deiros, David ;

Metzker, Mike ;

Muzny, Donna ;

Reid, Jeff ;

Wheeler, David ;

Wang, Jun ;

Li, Jingxiang ;

Jian, Min ;

Li, Guoqing ;

Li, Ruiqiang ;

Liang, Huiqing ;

Tian, Geng ;

Wang, Bo ;

Wang, Jian ;

Wang, Wei ;

Yang, Huanming ;

Zhang, Xiuqing ;

Zheng, Huisong ;

Lander, Eric S. ;

Altshuler, David L. ;

Ambrogio, Lauren ;

Bloom, Toby ;

Cibulskis, Kristian ;

Fennell, Tim J. ;

Gabriel, Stacey B. .

NATURE, 2010, 467 (7319) :1061-1073

[4] An integrated map of genetic variation from 1,092 human genomes [J].

Altshuler, David M. ;

Durbin, Richard M. ;

Abecasis, Goncalo R. ;

Bentley, David R. ;

Chakravarti, Aravinda ;

Clark, Andrew G. ;

Donnelly, Peter ;

Eichler, Evan E. ;

Flicek, Paul ;

Gabriel, Stacey B. ;

Gibbs, Richard A. ;

Green, Eric D. ;

Hurles, Matthew E. ;

Knoppers, Bartha M. ;

Korbel, Jan O. ;

Lander, Eric S. ;

Lee, Charles ;

Lehrach, Hans ;

Mardis, Elaine R. ;

Marth, Gabor T. ;

McVean, Gil A. ;

Nickerson, Deborah A. ;

Schmidt, Jeanette P. ;

Sherry, Stephen T. ;

Wang, Jun ;

Wilson, Richard K. ;

Gibbs, Richard A. ;

Dinh, Huyen ;

Kovar, Christie ;

Lee, Sandra ;

Lewis, Lora ;

Muzny, Donna ;

Reid, Jeff ;

Wang, Min ;

Wang, Jun ;

Fang, Xiaodong ;

Guo, Xiaosen ;

Jian, Min ;

Jiang, Hui ;

Jin, Xin ;

Li, Guoqing ;

Li, Jingxiang ;

Li, Yingrui ;

Li, Zhuo ;

Liu, Xiao ;

Lu, Yao ;

Ma, Xuedi ;

Su, Zhe ;

Tai, Shuaishuai ;

Tang, Meifang .

NATURE, 2012, 491 (7422) :56-65

[5]

[Anonymous], PHARMACOGENOM J

[6]

[Anonymous], 2012, R LANG ENV STAT COMP

[7]

[Anonymous], GUID DIAGN MAN ASTHM

[8] HLA antigens and asthma in Greeks [J].

Apostolakis, J ;

Toumbis, M ;

Konstantopoulos, K ;

Kamaroulias, D ;

Anagnostakis, J ;

Georgoulias, V ;

Fessas, P ;

Zervas, J .

RESPIRATORY MEDICINE, 1996, 90 (04) :201-204

[9] Fast and accurate inference of local ancestry in Latino populations [J].

Baran, Yael ;

Pasaniuc, Bogdan ;

Sankararaman, Sriram ;

Torgerson, Dara G. ;

Gignoux, Christopher ;

Eng, Celeste ;

Rodriguez-Cintron, William ;

Chapela, Rocio ;

Ford, Jean G. ;

Avila, Pedro C. ;

Rodriguez-Santana, Jose ;

Burchard, Esteban Gonzalez ;

Halperin, Eran .

BIOINFORMATICS, 2012, 28 (10) :1359-1367

[10] PCAdmix: Principal Components-Based Assignment of Ancestry along Each Chromosome in Individuals with Admixed Ancestry from Two or More Populations [J].

Brisbin, Abra ;

Bryc, Katarzyna ;

Byrnes, Jake ;

Zakharia, Fouad ;

Omberg, Larsson ;

Degenhardt, Jeremiah ;

Reynolds, Andrew ;

Ostrer, Harry ;

Mezey, Jason G. ;

Bustamante, Carlos D. .

HUMAN BIOLOGY, 2012, 84 (04) :343-364

← 1 2 3 4 5 6 7 →