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|Title:||Asthma-Susceptibility Variants Identified Using Probands in Case-Control and Family-Based Analyses|
|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;Celedón, Juan C;Lange, Christoph;O'Connor, George T;Raby, Benjamin A;Silverman, Edwin K;Weiss, Scott T|
|Description:||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.|
National Heart, Lung, and Blood Insitute and the National Institutes of Health (U01 HL075419, U01 HL65899, PO1 HL083069, R01 HL086601, T32 HL07437, N01-HC-25195); National Institutes of Health (R37 HL066289, HL04370, R01 HL087680; National Library of Medicine (2T15LM007092-16); Affymetrix Inc. (N02-HL-6-4278); Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center; Young Clinical Scientist Award from the Flight Attendant Medical Research Institute
|Standard no:||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)|
|Appears in Collections:||School of Medicine|
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