Table 1. Studies using a hypothesis-driven approach.

Definition of exacerbation	Gene	Associated variants	Reference Number
ER visit or hospitalization	IL13	rs1800925	15
# The mutant allele of rs1800925 was inversely associated with AEs in Costa Rican children with asthma (P=0.069). Although this SNP was not associated with AEs among all non-Hispanic white children, it was associated with increased risk of AEs among children on ICSs (P=0.02) in the CAMP trial.
ICU care, ER visit or hospitalization	IL4RA	rs1805011, rs1801275	17
# The mutant allele of rs1805011 (E375A) and rs1801275 (Q551R), which were more common in African Americans, was associated with a history of AEs in two cohorts of adult asthmatics enrolled in US.
Hospitalization	CHI3L1	rs4950928	19
# The mutant allele of rs4950928 conferred protections against AEs (OR=0.62, 95%CI=0.41–0.92, P=0.018) in children and young adults with asthma in Scotland.
Hospitalization, SA or OSB	ORMDL3	s7216389	21
# The SPN in ORMDL3 rs7216389 was genotyped in 376 children born to mothers with asthma and enrolled in the Copenhagen Prospective Study. This SNP was significantly associated with AEs (hazard ratio=2.66, 95%CI=1.58-4.48, P=0.0002). The increased risk of AEs persisted from 1 to 6 years of age.

AE, Asthma exacerbation; CAMP, Childhood asthma management program; CI, Confidence interval; ER, Emergency room; ICU, Intensive care unit; ICS, Inhaled corticosteroid; OR, Odds ratio; OSB, Oral steroid burst; SA, School absence; SNP, Single nucleotide polymorphism.