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
16380917
TITLE
Robust estimation of experimentwise P values applied to a genome scan of multiple asthma traits identifies a new region of significant linkage on chromosome 20q13.
ABSTRACT
Over 30 genomic regions show linkage to asthma traits. Six asthma genes have been cloned, but the putative loci in many linked regions have not been identified. To search for asthma susceptibility loci, we performed genomewide univariate linkage analyses of seven asthma traits, using 202 Australian families ascertained through a twin proband. House-dust mite sensitivity (Dpter) exceeded the empirical threshold for significant linkage at 102 cM on chromosome 20q13, near marker D20S173 (empirical pointwise P = .00001 and genomewide P = .005, both uncorrected for multiple-trait testing). Atopy, bronchial hyperresponsiveness (BHR), and forced expiratory volume in 1 s (FEV1) were also linked to this region. In addition, 16 regions were linked to at least one trait at the suggestive level, including 12q24, which has consistently shown linkage to asthma traits in other studies. Some regions were expected to be false-positives arising from multiple-trait testing. To address this, we developed a new approach to estimate genomewide significance that accounts for multiple-trait testing and for correlation between traits and that does not require a Bonferroni correction. With this approach, Dpter remained significantly linked to 20q13 (empirical genomewide P = .042), and airway obstruction remained linked to 12q24 at the suggestive level. Finally, we extended this method to show that the linkage of Dpter, atopy, BHR, FEV1, asthma, and airway obstruction to chromosome 20q13 is unlikely to be due to chance and may result from a quantitative trait locus in this region that affects several of these traits.
DATE PUBLISHED
2005 Dec
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2005/07/18
accepted 2005/09/08
aheadofprint 2005/10/14
pubmed 2005/12/29 09:00
medline 2006/01/31 09:00
entrez 2005/12/29 09:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Ferreira MA Ferreira Manuel A R MA Queensland Institute of Medical Research, Brisbane, Australia. manuelF@qimr.edu.au
O'Gorman L O'Gorman Louise L
Le Souëf P Le Souëf Peter P
Burton PR Burton Paul R PR
Toelle BG Toelle Brett G BG
Robertson CF Robertson Colin F CF
Visscher PM Visscher Peter M PM
Martin NG Martin Nicholas G NG
Duffy DL Duffy David L DL
INVESTIGATORS
JOURNAL
VOLUME: 77
ISSUE: 6
TITLE: American journal of human genetics
ISOABBREVIATION: Am. J. Hum. Genet.
YEAR: 2005
MONTH: Dec
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Print
ISSN: 0002-9297
ISSNTYPE: Print
MEDLINE JOURNAL
MEDLINETA: Am J Hum Genet
COUNTRY: United States
ISSNLINKING: 0002-9297
NLMUNIQUEID: 0370475
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Comparative Study
Journal Article
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GRANTS
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adult
Aged
Animals
Asthma physiopathology
Bronchial Hyperreactivity genetics
Chromosome Mapping genetics
Chromosomes, Human, Pair 12 genetics
Chromosomes, Human, Pair 20 genetics
Dermatophagoides pteronyssinus immunology
Female immunology
Forced Expiratory Volume genetics
Genetic Linkage genetics
Genetic Markers genetics
Genome, Human genetics
Humans genetics
Hypersensitivity, Immediate genetics
Male genetics
Middle Aged genetics
Probability genetics
Quantitative Trait Loci genetics
Skin Tests genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 Genetic Markers
OTHER ID's
OTHERID SOURCE
PMC1285164 NLM