Asthma-susceptibility variants identified using probands in case-control and family-based analyses.
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.
Himes
Blanca E
BE
Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA, USA.
Lasky-Su
Jessica
J
Wu
Ann C
AC
Wilk
Jemma B
JB
Hunninghake
Gary M
GM
Klanderman
Barbara
B
Murphy
Amy J
AJ
Lazarus
Ross
R
Soto-Quiros
Manuel E
ME
Avila
Lydiana
L
Celedón
Juan C
JC
Lange
Christoph
C
O'Connor
George T
GT
Raby
Benjamin A
BA
Silverman
Edwin K
EK
Weiss
Scott T
ST
D001249:Asthma / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D005190:Family; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012107:Research Design