Asthma-Susceptibility Variants Identified Using Probands in Case-Control and Family-Based Analyses
Date
2010-8-10
Authors
Himes, Blanca E.
Lasky-Su, Jessica
Wu, Ann C.
Wilk, Jemma B.
Hunninghake, Gary M.
Klanderman, Barbara
Murphy, Amy J.
Lazarus, Ross
Soto-Quiros, Manuel E.
Avila, Lydiana
Version
OA Version
Citation
Himes, Blanca E, Jessica Lasky-Su, Ann C Wu, Jemma B Wilk, Gary M Hunninghake, Barbara Klanderman, Amy J Murphy, Ross Lazarus, Manuel E Soto-Quiros, Lydiana Avila, Juan C Celedón, Christoph Lange, George T O'Connor, Benjamin A Raby, Edwin K Silverman, Scott T Weiss. "Asthma-susceptibility variants identified using probands in case-control and family-based analyses" BMC Medical Genetics 11:122. (2010)
Abstract
BACKGROUND: Asthma is a chronic respiratory disease whose genetic basis has been explored for over two decades, most recently via genome-wide association studies. We sought to find asthma-susceptibility variants by using probands from a single population in both family-based and case-control association designs. METHODS: We used probands from the Childhood Asthma Management Program (CAMP) in two primary genome-wide association study designs: (1) probands were combined with publicly available population controls in a case-control design, and (2) probands and their parents were used in a family-based design. We followed a two-stage replication process utilizing three independent populations to validate our primary findings. RESULTS: We found that single nucleotide polymorphisms with similar case-control and family-based association results were more likely to replicate in the independent populations, than those with the smallest p-values in either the case-control or family-based design alone. The single nucleotide polymorphism that showed the strongest evidence for association to asthma was rs17572584, which replicated in 2/3 independent populations with an overall p-value among replication populations of 3.5E-05. This variant is near a gene that encodes an enzyme that has been implicated to act coordinately with modulators of Th2 cell differentiation and is expressed in human lung. CONCLUSIONS: Our results suggest that using probands from family-based studies in case-control designs, and combining results of both family-based and case-control approaches, may be a way to augment our ability to find SNPs associated with asthma and other complex diseases.
Description
License
Copyright 2010 Himes et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.