Genetics of Asthma and Hay Fever in Australian Twins

Duffy, David L.; Martin, Nicholas G.; Battistutta, Diana; Hopper, John L.; Mathews, John D.

doi:10.1164/ajrccm/142.6_pt_1.1351

Cited by 470 publications

(316 citation statements)

References 26 publications

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“…17 The use of twins also increases capacity over population-based studies to conduct multivariate analyses to decipher complex relationships between genes and pleiotropic effects. 18,19 A significant challenge in the application of high-throughput expression profiling of unrelated individuals is the inherent variation due to differences in genetic, ethnic and demographic variables. [20][21][22] Clearly, a twin study design offers significant advantages in dealing with these sources of variation in disease genetics.…”

Section: Introductionmentioning

confidence: 99%

Expression profiling in monozygotic twins discordant for bipolar disorder reveals dysregulation of the WNT signalling pathway

et al. 2007

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To identify genes dysregulated in bipolar disorder (BD1), we carried out global gene expression profiling using whole-genome microarrays. To minimize genetic variation in gene expression levels between cases and controls, we compared expression profiles in lymphoblastoid cell lines from monozygotic twin pairs discordant for the disease. We identified 82 genes that were differentially expressed by X1.3-fold in three BD1 cases compared to their co-twins, and which were statistically (Pp0.05) differentially expressed between the groups of BD1 cases and controls. Using quantitative reverse transcriptasepolymerase chain reaction, we confirmed the differential expression of some of these genes, including: KCNK1, MAL, PFN2, TCF7, PGK1 and PI4KCB, in at least two of the twin pairs. In contrast to the findings of a previous study by Kakiuchi and colleagues with similar discordant BD1 twin design, our data do not support the dysregulation of XBP1 and HSPA5. From pathway and gene ontology analysis, we identified upregulation of the WNT signalling pathway and the biological process of apoptosis. The differentially regulated genes and pathways identified in this study may provide insights into the biology of BD1.

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Section: Introductionmentioning

confidence: 99%

Expression profiling in monozygotic twins discordant for bipolar disorder reveals dysregulation of the WNT signalling pathway

et al. 2007

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“…4 AR may result from genetic determinants common to asthma, but there may be also genetic alterations specific to each of these phenotypes, as indicated by twin studies. 5,6 As for asthma, AR is strongly associated with atopy, with most subjects having rhinitis being atopic, while only a part of atopic subjects suffer from rhinitis. Genetic determinants shared by asthma and AR are likely to result in part from the atopic component of these two diseases.…”

Section: Introductionmentioning

confidence: 99%

Genome screen in the French EGEA study: detection of linked regions shared or not shared by allergic rhinitis and asthma

et al. 2005

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In the sample of 295 French EGEA families with at least one asthmatic subject, a genome screen was conducted to identify potential linkage regions specific either to allergic rhinitis (AR) or to asthma as well as those shared by the two diseases. Two binary rhinitis phenotypes based on (1) diagnosis (AR bin1 ) and (2) symptoms (AR bin2 ) and a categorical ordered trait (AR cat ) were considered. Asthma phenotype was based on answers to a standardized questionnaire plus the presence of bronchial hyper-responsiveness. Linkage analyses were conducted using the maximum likelihood binomial (MLB) method. These analyses provided potential evidence for linkage to three regions in the whole sample: 1p31 for the phenotype defined by AR bin2 plus asthma (P ¼ 0.00016), 2q32 for AR bin2 (P ¼ 0.00016) and 3p24-p14 for AR cat (P ¼ 0.001). Two other regions were detected in the subset of 185 families with at most one asthmatic sib: 9p22 and 9q22-q34 for AR bin1 (P ¼ 0.001 and 0.0007, respectively). No region showed evidence for linkage to asthma without being also linked to AR. While 1p31 may contain a genetic determinant common to asthma and AR, 2q32, 3p24-p14, 9p22 and 9q22-q34 are more likely to harbor genetic factors specific to AR. Genes and Immunity (2005) 6, 95-102.

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“…Asthma is highly heritable, 2 and many centres are now involved in studies to discover the genetic basis of asthma susceptibility. 3 The asthma phenotype is complex.…”

Section: Introductionmentioning

confidence: 99%

Association between quantitative traits underlying asthma and the HLA-DRB1 locus in a family-based population sample

et al. 2001

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The region of human chromosome 6 containing the MHC has been identified as influencing asthma and atopy (allergy) by several genome-wide searches. The MHC contains many genes with potential effects on innate and specific immunity. As a first step in dissecting MHC influences on asthma and its underlying quantitative phenotypes, we have examined the HLA-DRB1 locus in a population sample consisting of 1004 individuals from 230 families from the rural Australian town of Busselton. The locus was strongly associated with the (log e ) total serum IgE concentration, accounting for 4.0% of the s 2 (variance) in that trait (multiallelic test, P=0.00001). The locus also influenced specific IgE titres to common allergens (multi-allelic tests, 2.8% s 2 for the house dust mite allergen Der p I, P=0.0013; 3.0% of s 2 for Der p II, P=0.0007; and 2.1% of s 2 for the cat allergen Fel d I, P=0.014). No associations were found to the categorical phenotype of asthma, or to the quantitative traits of peripheral blood eosinophil counts and bronchial hyper-responsiveness. Transmission disequilibrium tests excluded genetic admixture as a cause of false-positive findings. The results indicate that HLA-DRB1 alleles modulate the total serum IgE concentration and IgE responses to allergens, but do not account for the previous observations of linkage of asthma to the MHC. European Journal of Human Genetics (2001) 9, 341 ± 346.

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Genetics of Asthma and Hay Fever in Australian Twins

Cited by 470 publications

References 26 publications

Expression profiling in monozygotic twins discordant for bipolar disorder reveals dysregulation of the WNT signalling pathway

Expression profiling in monozygotic twins discordant for bipolar disorder reveals dysregulation of the WNT signalling pathway

Genome screen in the French EGEA study: detection of linked regions shared or not shared by allergic rhinitis and asthma

Association between quantitative traits underlying asthma and the HLA-DRB1 locus in a family-based population sample

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