Pooling data and linkage analysis in the chromosome 5q candidate region for asthma.

Abstract:

:We investigated a variety of methods for pooling data from eight data sets (n = 5,424 subjects) to validate evidence for linkage of markers in the cytokine cluster on chromosome 5q31-33 to asthma and asthma-associated phenotypes. Chromosome 5 markers were integrated into current genetic linkage and physical maps, and a consensus map was constructed to facilitate effective data pooling. To provide more informative phenotypes with better distributional properties, variance component models were fitted using Gibbs sampling methods in order to generate residual additive genetic effects, or sigma-squared-A-random-effects (SSARs), which were used as derived phenotypes in subsequent linkage analyses. Multipoint estimates of alleles shared identically by descent (IBD) were computed for all full sibling pairs. Linkage analyses were performed with a new Haseman-Elston method that uses generalized-least-squares and a weighted combination of the mean-corrected trait-sum squared and trait-difference squared as the dependent variable. Analyses were performed with all data sets pooled together, and also separately with the resulting linkage statistics pooled by several meta-analytic methods. Our results provide no significant evidence that loci conferring susceptibility to asthma affection or atopy, as measured by total serum IgE levels, are present in the 5q31-33 region. This study has provided a clearer understanding of the significance, or lack of significance, of the 5q31-33 region in asthma genetics for the phenotypes studied.

journal_name

Genet Epidemiol

journal_title

Genetic epidemiology

authors

Jacobs KB,Burton PR,Iyengar SK,Elston RC,Palmer LJ

doi

10.1002/gepi.2001.21.s1.s103

subject

Has Abstract

pub_date

2001-01-01 00:00:00

pages

S103-8

eissn

0741-0395

issn

1098-2272

journal_volume

21 Suppl 1

pub_type

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