Quantitative linkage genome scan for atopy in a large collection of Caucasian families

Bradley T. Webb, Edwin van den Oord, Anthony Akkari, Steve Wilton, Tina Ly, Rachael Duv, Kathleen C. Barnes, Karin Carlsen, Jorrit Gerritsen, Warren Lenney, Michael Silverman, Peter Sly, John Sundy, John Tsanakas, Andrea von Berg, Moira Whyte, Malcolm Blumenthal, Jorgen Vestbo, Lefkos Middleton, Peter J. HelmsWayne H. Anderson, Sreekumar G. Pillai*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Quantitative phenotypes correlated with a complex disorder offer increased power to detect linkage in comparison to affected-unaffected classifications. Asthma is a complex disorder characterized by periods of bronchial obstruction and increased bronchial hyper reactivity. In childhood and early adulthood, asthma is frequently associated also with quantitative measures of atopy. Genome wide quantitative multipoint linkage analysis was conducted for serum IgE levels and percentage of positive skin prick test (SPTper) using three large groups of families originally ascertained for asthma. In this report, 438 and 429 asthma families were informative for linkage using IgE and SPTper which represents 690 independent families. Suggestive linkage (LOD > 2) was found on chromosomes 1, 3, and 8q with maximum LODs of 2.34 (IgE), 2.03 (SPTper), and 2.25 (IgE) near markers D1S1653, D3S2322-D3S1764, and D8S2324, respectively. The results from chromosomes 1 and 3 replicate previous reports of linkage. We also replicate linkage to 5q with peak LODs of 1.96 (SPTper) and 1.77 (IgE) at or near marker D5S1480. Our results provide further evidence implicating chromosomes 1, 3, and 5q. The current report represents one of the biggest genome scans so far reported for asthma related phenotypes. This study also demonstrates the utility of increased sample sizes and quantitative phenotypes in linkage analysis of complex disorders.

Original languageEnglish
Pages (from-to)83-92
Number of pages10
JournalHuman Genetics
Volume121
Issue number1
DOIs
Publication statusPublished - Mar 2007

Keywords

  • MAJOR SUSCEPTIBILITY LOCUS
  • WIDE SEARCH
  • POSITIONAL CLONING
  • ASTHMA PHENOTYPES
  • SPINK5 GENE
  • ASSOCIATION
  • POPULATION
  • DERMATITIS
  • TRAITS
  • POLYMORPHISMS

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