Genome-wide association study identifies multiple susceptibility loci for pulmonary fibrosis

被引：588

作者：

Fingerlin, Tasha E. ^{[1
]}

Murphy, Elissa ^{[2
]}

Zhang, Weiming ^{[1
]}

Peljto, Anna L. ^{[1
]}

Brown, Kevin K. ^{[2
,3
]}

Steele, Mark P. ^{[4
]}

Loyd, James E. ^{[4
]}

Cosgrove, Gregory P. ^{[2
,3
]}

Lynch, David ^{[3
]}

Groshong, Steve ^{[3
]}

Collard, Harold R. ^{[5
]}

Wolters, Paul J. ^{[5
]}

Bradford, Williamson Z. ^{[6
]}

Kossen, Karl ^{[6
]}

Seiwert, Scott D. ^{[6
]}

du Bois, Roland M. ^{[7
,8
]}

Garcia, Christine Kim ^{[9
]}

Devine, Megan S. ^{[9
]}

Gudmundsson, Gunnar ^{[10
,11
,12
,13
]}

Isaksson, Helgi J. ^{[10
,11
,12
,13
]}

Kaminski, Naftali ^{[14
]}

Zhang, Yingze ^{[14
]}

Gibson, Kevin F. ^{[14
]}

Lancaster, Lisa H. ^{[4
]}

Cogan, Joy D. ^{[4
]}

Mason, Wendi R. ^{[4
]}

Maher, Toby M. ^{[7
,8
]}

Molyneaux, Philip L. ^{[7
,8
]}

Wells, Athol U. ^{[7
,8
]}

Moffatt, Miriam F. ^{[7
,8
]}

Selman, Moises ^{[15
]}

Pardo, Annie ^{[16
]}

Kim, Dong Soon ^{[17
]}

Crapo, James D. ^{[2
,3
]}

Make, Barry J. ^{[2
,3
]}

Regan, Elizabeth A. ^{[3
]}

Walek, Dinesha S. ^{[18
]}

Daniel, Jerry J. ^{[18
]}

Kamatani, Yoichiro ^{[19
]}

Zelenika, Diana ^{[20
]}

Smith, Keith ^{[2
]}

McKean, David ^{[2
]}

Pedersen, Brent S. ^{[2
]}

Talbert, Janet ^{[3
]}

Kidd, Raven N. ^{[21
]}

Markin, Cheryl R. ^{[4
]}

Beckman, Kenneth B. ^{[18
]}

Lathrop, Mark ^{[19
,20
]}

Schwarz, Marvin I. ^{[2
,3
]}

Schwartz, David A. ^{[2
,3
,22
]}

机构：

[1] Univ Colorado Denver, Sch Publ Hlth, Denver, CO USA

[2] Univ Colorado Denver, Sch Med, Dept Med, Denver, CO USA

[3] Natl Jewish Hlth, Dept Med, Denver, CO USA

[4] Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37212 USA

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

[6] InterMune, Brisbane, Qld, Australia

[7] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London, England

[8] Royal Brompton Hosp, London SW3 6LY, England

[9] Univ Texas Southwestern, Dept Med, Dallas, TX USA

[10] Landspitali Univ Hosp, Dept Med, Reykjavik, Iceland

[11] Landspitali Univ Hosp, Dept Pathol, Reykjavik, Iceland

[12] Univ Iceland, Fac Med, Dept Med, Reykjavik, Iceland

[13] Univ Iceland, Fac Med, Dept Pathol, Reykjavik, Iceland

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

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

[16] Univ Nacl Autonoma Mexico, Fac Ciencias, Mexico City 04510, DF, Mexico

[17] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Pulm, Seoul, South Korea

[18] Univ Minnesota, Biomed Genom Ctr, Minneapolis, MN USA

[19] Ctr Etud Polymorphisme Humain, Fdn Jean Dausset, F-75010 Paris, France

[20] CEA, Ctr Natl Genotypage, Inst Genom, Evry, France

[21] Quintiles, Parsippany, NJ USA

[22] Univ Colorado Denver, Dept Immunol, Denver, CO USA

来源：

NATURE GENETICS | 2013年 / 45卷 / 06期

关键词：

SURFACTANT PROTEIN-C; GENOTYPE IMPUTATION; SIGNALING PATHWAY; MUTATIONS; PROMOTER; CATENIN; DISEASE; SCAN; HETEROZYGOSITY; METAANALYSIS;

D O I：

10.1038/ng.2609

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

We performed a genome-wide association study of non-Hispanic, white individuals with fibrotic idiopathic interstitial pneumonias (IIPs; n = 1,616) and controls (n = 4,683), with follow-up replication analyses in 876 cases and 1,890 controls. We confirmed association with TERT at 5p15, MUC5B at 11p15 and the 3q26 region near TERC, and we identified seven newly associated loci (P-meta = 2.4 x 10(-8) to 1.1 x 10(-19)), including FAM13A (4q22), DSP (6p24), OBFC1 (10q24), ATP11A (13q34), DPP9 (19p13) and chromosomal regions 7q22 and 15q14-15. Our results suggest that genes involved in host defense, cell-cell adhesion and DNA repair contribute to risk of fibrotic IIPs.

引用

页码：613 / +

页数：11

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