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. Author manuscript; available in PMC: 2023 Nov 11.
Published in final edited form as: J Investig Allergol Clin Immunol. 2022 Nov 24;33(2):76–94. doi: 10.18176/jiaci.0878

Table 1.

Main findings and characteristics of candidate-gene studies for AEs conducted from 15th November, 2018 to 1st October, 2022.

rsID (Gene) Subjects Phenotype EA/EG Effect size (95%CI) or (SE) P PMID [reference]
rs295137 (SPATS2L) 491 European children with moderate-to-severe asthma presenting to the ER Hosp/active asthma management ≥8 h in ER after OCS/return visit within 72 h for one of events after presenting to the ER T OR: 1.77 (1.17, 2.68) 0.006 30644648 [50]
rs7037276 (IL33) T OR: 0.55 (0.33, 0.90) 0.02
rs1342326 (IL33) C OR: 0.52 (0.32, 0.86) 0.01
rs16986718 (NLRP4) 1-year longitudinal study of 1,454 Korean subjects with asthma, including 955 never-smokers Number of ER visits/Hosp/OCS/rescue bronchodilator/increase of asthma medication G Increased annual exacerbation episodes 0.001 30526007
[51]
≥2 exacerbations events vs one/none OR: 2.56 (NA) 6.7×10−5
SNP × pack/years on exacerbations NA 0.014
rs1799768 (SERPINE1) 265 subjects (48% European, 43% African/African American) with poorly controlled asthma enrolled in a randomized clinical trial of soy isoflavones. OCS 4G4G/4G5G vs 5G/5G IRR: 2.57 (1.09–6.07) 0.031 30707970
[52]
Soy isoflavones intake×SNP on OCS NA 0.005
Number of OCS events/person-year RR: 0.28 (0.12, 0.59) <0.001
rs7251960 (CEACAM3) Discovery: 456 Taiwanese children with asthma
Replication: 844 children with mild-to-moderate asthma recruited in the United States		 Discovery: Nocturnal wheezing/ cough or wheezing/dyspnea in the last 2 weeks.
Replication: Asthma-related limitation of activity/wheezing-induced nocturnal awakenings at least once a month in the last 2 months		 CT/TT vs CC ORDiscovery: 2.58 (1.65, 4.03)
ORReplication: 1.53 (1.03,2.31)		 3.12×10−5; 0.035 32606071
[53]
RSV × SNP on exacerbation. NA 0.03
rs1544410 (VDR) 657 Australian children (64.2% European) presenting to the ER with acute asthma/wheezing/ bronchiolitis Exacerbation severity Z-scores TT vs CC Increased severity scores 0.005 32380236
[54]
rs2228570 (VDR) Exacerbation severity Z-scores AA vs GG Increased severity scores 0.001
Lifetime Hosp for acute respiratory illnesses AG vs GG Increased severity scores 0.011
ADRB2 variants 832 children with asthma Hosp/ER visits/OCS in the last 6–12 months despite ICS plus LABA use Arg16/Gln27 vs Gly16/Glu27 1.40 (1.05,1.87) 0.022 34128573
[55]
Arg16/Gln27 vs Gly16/Gln27 1.43 (1.05–1.94) 0.023
rs67622929 (DNASE1L3) Discovery: 1,002 African American subjectss with asthma. Replication: 2,181 Hispanic/Latino children with asthma Hosp/ER visits/OCS in the last 12 months C ORDiscovery: 1.48 (1.18,1.87)
ORReplication: 1.18 (1.01,1.37)		 7.9×10−4; 0.03 33035569
[56]
rs11681246 (LTBP1) 2,681 European children Hosp/ER visits/OCS in the last 6–12 months despite ICS use G OR: 0.72 (0.63, 0.83) 3.28×10−6 32786158
[57]
rs76390075 (LTBP1) 1,347 Hispanic/Latino or African American children with asthma C OR: 0.40 (0.26, 0.63) 6.76×10−5
rs2660845 (LTA4H) Patients with asthma.
Discovery: 523 Europeans with early-onset asthma
R1: 2,514 Europeans with early-onset asthma
R2: 486 Hispanic/Latino children
R3: 71 African American children		 Hosp/ER visits/OCS in the last 6–12 months despite montelukast use G ORDiscovery: 2.92 (1.04,8.18)
ORR1: 1.02 (0.87,1.19)
ORR2: 1.04 (0.78,1.39)
ORR3: 0.27 (0.09,0.80)		 0.041
R1: 0.833
R2: 0.788
R3: 0.019		 34550981
[58]
rs2517955 (PGAP3) 3-year longitudinal study of 273 non-Hispanic white adolescents and adults with asthma Number of asthma-related ER visits/Hosp in 3 years C β: 1.05 (NA) 0.0034 32795586
[59]
rs1031458 (GSDMB) G β: −0.77 (NA) 0.028
rs3902920 (GSDMB) T β: −0.88 (NA) 0.012
rs13431828 (IL1RL1) 2,412 European, Hispanic/Latino or African American children Hosp/ER visits in the last 6–12 months despite ICS use C OR: 1.32 (1.08, 1.62) 0.02 31755552
[60]
OR: 1.31 (1.07, 1.59) 0.02
rs242941 (CRHR1) European adult patients with asthma (nDiscovery=597; nReplication: 9,842) Hosp/ER visits/OCS despite ICS use A RRDiscovery: 6.11 (NA)
RRReplication: 1.16 (NA)		 <0.005; 0.004 33428814
[61]
rs1134481 (TBXT) T RRDiscovery: 0.36 (NA)
RRReplication: 1.02 (NA)		 <0.005; 0.563
rs37973 (GLCCI1) G RRDiscovery: 1.88 (NA)
RRReplication: 0.82 (NA)		 <0.005; <0.005
rs1384006 (OXSR1) 1-year longitudinal study of 1,454 Korean subjects with asthma, including 955 never-smokers Number of ER visits/Hosp/OCS/rescue bronchodilator/increase of asthma medication C Increased annual exacerbation episodes 0.004 34983467
[62]
≥2 exacerbations events vs one/none OR: 0.36 (0.18, 0.72) 0.004
rs9665961 (BIRC3) * 5,710 European adults, 166 European children, 854 Hispanic/Latino children and 493 African American children with asthma Hosp/ER visits/OCS in the last 6–12 months despite ICS use/8% decrease in FEV1 in patients after 6 weeks of ICS therapy A OR: 0.81 (NA) 3.77×10−4 34971648
[63]
*

A total of 35 SNPs in linkage disequilibrium (r2≥0.8) were significantly associated with AEs on the sample size weighted meta-analysis based on p-values. For visual clarity, the most significant variant in the meta-analysis is shown here, accompanied by the odds ratio corresponding to the largest cohort contributing to the rs9665961 genotype data on the multi-ancestry meta-analysis. Abbreviation: β: Regression coefficient; CI: Confidence interval; EA/EG: Effect allele/genotype; ER: Emergency room; FEV1: Forced expiratory volume in the first second; Hosp: Hospitalizations; ICS: Inhaled corticosteroids; IRR: Incidence risk ratio; LABA: Long-acting beta2-agonists; NA: Not available; OCS: Oral corticosteroids use; OR: Odds ratio; RR: Relative risk; Rn: Replication study (number n); RSV: Respiratory syncytial virus; SE: Standard error of the beta coefficient; SNP: Single nucleotide polymorphism; P: P-value.