Significant evidence for linkage to chromosome 5q13 in a genome-wide scan for asthma in an extended pedigree resource

Department of Biomedical Informatics, Division of Genetic Epidemiology, University of Utah School of Medicine, Salt Lake City, UT 84112-5750, USA.
European journal of human genetics: EJHG (Impact Factor: 4.35). 01/2009; 17(5):636-43. DOI: 10.1038/ejhg.2008.236
Source: PubMed


Asthma is a multifactorial disease with undetermined genetic factors. We performed a genome-wide scan to identify predisposition loci for asthma. The asthma phenotype consisted of physician-confirmed presence or absence of asthma symptoms. We analyzed 81 extended Utah pedigrees ranging from three to six generations, including 742 affected individuals, ranging from 2 to 40 per pedigree. We performed parametric multipoint linkage analyses with dominant and recessive models. Our analysis revealed genome-wide significant evidence of linkage to region 5q13 (log of the odds ratio (LOD)=3.8, recessive model), and suggestive evidence for linkage to region 6p21 (LOD=2.1, dominant model). Both the 5q13 and 6p21 regions indicated in these analyses have been previously identified as regions of interest in other genome-wide scans for asthma-related phenotypes. The evidence of linkage at the 5q13 region represents the first significant evidence for linkage on a genome-wide basis for this locus. Linked pedigrees localize the region to approximately between 92.3-105.5 Mb.

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Available from: Lisa A Cannon-Albright, Oct 06, 2015
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    • "Results from MCLINK have shown a high degree of similarity to other MCMC linkage methods [44] and also to exact linkage methods and variance components linkage methods as applied to extended pedigrees [45]. MCLINK has been previously used to identify candidate genomic regions for a number of complex diseases in extended pedigrees [44,46-48]. Allele frequencies for the MCLINK analysis were estimated using all of the observed data. "
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    ABSTRACT: The latent p value is a recently proposed empirical method for assessing evidence against a null hypothesis in a stochastic system involving latent, unobservable variables. It is particularly applicable to genome-wide genetic linkage analysis for test statistics with poorly defined analytical distributions. We describe an implementation of the latent p value method and its application to a linkage analysis of asthma in 81 extended pedigrees containing 1,858 people genotyped at 533 microsatellite markers. We compare the performance of the latent p value method to a more conventional p value calculation. We also compare the performance of various linkage statistics within this pedigree resource. Using a novel linkage score referred to as the C-link statistic, our analysis provides strong evidence for a recessive gene influencing asthma on chromosome 5q13 (median latent p value = 0.03). We also demonstrate remarkable improvement in computational requirements compared to a more conventional empirical p value calculation. The latent p value method is indeed feasible and provides a computationally efficient means to evaluate evidence for linkage regardless of the choice of linkage statistic.
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