Unifying Candidate Gene and GWAS Approaches in Asthma

被引：77

作者：

Michel, Sven ^{[1
]}

Liang, Liming ^{[2
]}

Depner, Martin ^{[3
]}

Klopp, Norman ^{[4
]}

Ruether, Andreas ^{[5
]}

Kumar, Ashish ^{[6
]}

Schedel, Michaela ^{[1
]}

Vogelberg, Christian ^{[7
]}

von Mutius, Erika ^{[3
]}

von Berg, Andrea ^{[8
]}

Bufe, Albrecht ^{[9
]}

Rietschel, Ernst ^{[10
]}

Heinzmann, Andrea ^{[11
]}

Laub, Otto ^{[12
]}

Simma, Burkhard ^{[13
]}

Frischer, Thomas ^{[14
]}

Genuneit, Jon ^{[15
]}

Gut, Ivo G. ^{[16
,17
]}

Schreiber, Stefan

Lathrop, Mark ^{[16
]}

Illig, Thomas ^{[4
]}

Kabesch, Michael ^{[1
]}

机构：

[1] Hannover Med Sch, Ctr Pediat, Clin Pediat Pneumol Allergol & Neonatol, D-3000 Hannover, Germany

[2] Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA

[3] Univ Munich, Univ Childrens Hosp, Munich, Germany

[4] Helmholtz Ctr Munich, Inst Epidemiol, Neuherberg, Germany

[5] Univ Hosp Schleswig Holstein, Inst Clin Mol Biol, Kiel, Germany

[6] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England

[7] Tech Univ Dresden, Univ Childrens Hosp, Dresden, Germany

[8] Marien Hosp, Childrens Dept, Res Inst Prevent Allerg Dis, Wesel, Germany

[9] Ruhr Univ Bochum, Dept Expt Pneumol, Bochum, Germany

[10] Univ Cologne, Univ Childrens Hosp, Cologne, Germany

[11] Univ Freiburg, Univ Childrens Hosp, Freiburg, Germany

[12] Kinder & Jugendarztpraxis Laub, Rosenheim, Germany

[13] Landeskrankenhaus Feldkirch, Childrens Dept, Univ Teaching Hosp, Feldkirch, Austria

[14] Univ Childrens Hosp Vienna, Vienna, Austria

[15] Univ Ulm, Inst Epidemiol, Ulm, Germany

[16] Commissariat Energie Atom, Inst Genom, Ctr Natl Genotypage, Evry, France

[17] Ctr Nacl Anal Genom, Barcelona, Spain

来源：

PLOS ONE | 2010年 / 5卷 / 11期

关键词：

NECROSIS-FACTOR-ALPHA; ETHNICALLY DIVERSE POPULATIONS; GENOME-WIDE ASSOCIATION; CHILDHOOD ASTHMA; BRONCHIAL HYPERRESPONSIVENESS; RECEPTOR POLYMORPHISMS; ADAM33; POLYMORPHISMS; ATOPIC ASTHMA; ADULT ASTHMA; BIRTH COHORT;

D O I：

10.1371/journal.pone.0013894

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The first genome wide association study (GWAS) for childhood asthma identified a novel major susceptibility locus on chromosome 17q21 harboring the ORMDL3 gene, but the role of previous asthma candidate genes was not specifically analyzed in this GWAS. We systematically identified 89 SNPs in 14 candidate genes previously associated with asthma in >3 independent study populations. We re-genotyped 39 SNPs in these genes not covered by GWAS performed in 703 asthmatics and 658 reference children. Genotyping data were compared to imputation data derived from Illumina HumanHap300 chip genotyping. Results were combined to analyze 566 SNPs covering all 14 candidate gene loci. Genotyped polymorphisms in ADAM33, GSTP1 and VDR showed effects with p-values <0.0035 (corrected for multiple testing). Combining genotyping and imputation, polymorphisms in DPP10, EDN1, IL12B, IL13, IL4, IL4R and TNF showed associations at a significance level between p = 0.05 and p = 0.0035. These data indicate that (a) GWAS coverage is insufficient for many asthma candidate genes, (b) imputation based on these data is reliable but incomplete, and (c) SNPs in three previously identified asthma candidate genes replicate in our GWAS population with significance after correction for multiple testing in 14 genes.

引用

页数：10

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