Genetic Epidemiology, Psychiatric Genetics, Asthma Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
21150878
TITLE
Association between ORMDL3, IL1RL1 and a deletion on chromosome 17q21 with asthma risk in Australia.
ABSTRACT
Genome-wide association studies followed by replication provide a powerful approach to map genetic risk factors for asthma. We sought to search for new variants associated with asthma and attempt to replicate the association with four loci reported previously (ORMDL3, PDE4D, DENND1B and IL1RL1). Genome-wide association analyses of individual single nucleotide polymorphisms (SNPs), rare copy number variants (CNVs) and overall CNV burden were carried out in 986 asthma cases and 1846 asthma-free controls from Australia. The most-associated locus in the SNP analysis was ORMDL3 (rs6503525, P = 4.8 × 10⁻⁷). Five other loci were associated with P < 10⁻⁵, most notably the chemokine CXC motif ligand 14 (CXCL14) gene (rs31263, P = 7.8 × 10⁻⁶). We found no evidence for association with the specific risk variants reported recently for PDE4D, DENND1B and ILR1L1. However, a variant in IL1RL1 that is in low linkage disequilibrium with that reported previously was associated with asthma risk after accounting for all variants tested (rs10197862, gene wide P = 0.01). This association replicated convincingly in an independent cohort (P = 2.4 × 10⁻⁴). A 300-kb deletion on chromosome 17q21 was associated with asthma risk, but this did not reach experiment-wide significance. Asthma cases and controls had comparable CNV rates, length and number of genes affected by deletions or duplications. In conclusion, we confirm the association between asthma risk and variants in ORMDL3 and identify a novel risk variant in IL1RL1. Follow-up of the 17q21 deletion in larger cohorts is warranted.
DATE PUBLISHED
2011 Apr
HISTORY
PUBSTATUS PUBSTATUSDATE
aheadofprint 2010/12/08
entrez 2010/12/15 06:00
pubmed 2010/12/15 06:00
medline 2011/07/08 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Ferreira MA Ferreira Manuel A R MA Queensland Institute of Medical Research, Brisbane, QLD, Australia. manuel.ferreira@qimr.edu.au
McRae AF McRae Allan F AF
Medland SE Medland Sarah E SE
Nyholt DR Nyholt Dale R DR
Gordon SD Gordon Scott D SD
Wright MJ Wright Margaret J MJ
Henders AK Henders Anjali K AK
Madden PA Madden Pamela A PA
Visscher PM Visscher Peter M PM
Wray NR Wray Naomi R NR
Heath AC Heath Andrew C AC
Montgomery GW Montgomery Grant W GW
Duffy DL Duffy David L DL
Martin NG Martin Nicholas G NG
INVESTIGATORS
JOURNAL
VOLUME: 19
ISSUE: 4
TITLE: European journal of human genetics : EJHG
ISOABBREVIATION: Eur. J. Hum. Genet.
YEAR: 2011
MONTH: Apr
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1476-5438
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Eur J Hum Genet
COUNTRY: England
ISSNLINKING: 1018-4813
NLMUNIQUEID: 9302235
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GRANTS
GRANTID AGENCY COUNTRY
AA07535 NIAAA NIH HHS United States
AA07728 NIAAA NIH HHS United States
AA10248 NIAAA NIH HHS United States
AA11998 NIAAA NIH HHS United States
AA13320 NIAAA NIH HHS United States
AA13321 NIAAA NIH HHS United States
AA13326 NIAAA NIH HHS United States
AA14041 NIAAA NIH HHS United States
DA12854 NIDA NIH HHS United States
K05 AA017688 NIAAA NIH HHS United States
MH66206 NIMH NIH HHS United States
R01 DA012854 NIDA NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Asthma genetics
Australia epidemiology
Chromosomes, Human, Pair 17 genetics
Cyclic Nucleotide Phosphodiesterases, Type 3 genetics
Cyclic Nucleotide Phosphodiesterases, Type 4 genetics
DNA Copy Number Variations genetics
Genetic Predisposition to Disease genetics
Genome-Wide Association Study genetics
Humans genetics
Membrane Proteins genetics
Polymorphism, Single Nucleotide genetics
Receptors, Cell Surface genetics
Sequence Deletion genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 IL1RL1 protein, human
0 Membrane Proteins
0 ORMDL3 protein, human
0 Receptors, Cell Surface
EC 3.1.4.17 Cyclic Nucleotide Phosphodiesterases, Type 3
EC 3.1.4.17 Cyclic Nucleotide Phosphodiesterases, Type 4
EC 3.1.4.17 PDE4D protein, human
OTHER ID's
OTHERID SOURCE
PMC3060316 NLM