Table 3.
Association between Early-Onset Asthma (Age < 5 yr) and Haplotypes among African American Study Participants
| Haplotype* | Meta-analysis |
SAPPHIRE |
SAGE II |
GCPD-A |
|||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| OR† | P Value | Haplotype Frequency in Case Patients/Control Subjects | OR† | P Value | Haplotype Frequency in Case Patients/Control Subjects | OR† | P Value | Haplotype Frequency in Case Patients/Control Subjects | OR† | P Value | |
| 1: M-M-M-M (G-G-C-T) | Ref | — | 0.751/0.701 | Ref | — | 0.724/0.697 | Ref | — | 0.728/0.694 | Ref | — |
| 2: m-M-M-M (A-G-C-T) | 0.91 (0.81–1.03) | 0.151 | 0.098/0.112 | 0.86 (0.69–1.05) | 0.143 | 0.102/0.101 | 1.02 (0.75–1.41) | 0.887 | 0.113/0.124 | 0.92 (0.77–1.10) | 0.374 |
| 3: M-M-m-M (G-G-T-T) | 1.01 (0.82–1.24) | 0.948 | 0.032/0.033 | 0.90 (0.62–1.29) | 0.556 | 0.043/0.037 | 1.15 (0.71–1.85) | 0.564 | 0.032/0.032 | 1.04 (0.76–1.41) | 0.826 |
| 4: M-m-m-M (G-A-T-T) | 0.99 (0.63–1.57) | 0.978 | 0.009/0.007 | 1.01 (0.47–2.15) | 0.987 | 0.008/0.002 | 3.35 (0.59–18.93) | 0.172 | 0.008/0.008 | 0.85 (0.46–1.56) | 0.598 |
| 5: M-m-m-m (G-A-T-C) | 0.73 (0.65–0.82) | 8.94 × 10−8 | 0.110/0.147 | 0.67 (0.55–0.81) | 6.33 × 10−5 | 0.123/0.164 | 0.71 (0.54–0.94) | 0.017 | 0.116/0.142 | 0.78 (0.66–0.92) | 4.78 × 10−4 |
Definition of abbreviations: GCPD-A = Study of the Genetic Causes of Complex Pediatric Disorders–Asthma; OR = odds ratio; Ref = reference; SAGE II = Study of African Americans, Asthma, Genes and Environment; SAPPHIRE = Study of Asthma Phenotypes and Pharmacogenomic Interactions by Race–Ethnicity.
Haplotypes were based on functional polymorphisms within the African 17q12–21.1 haplotype block containing the early-onset asthma signal. Haplotype order is as follows: rs16965388 (G is the M, and A is the m); rs2305480 (G is the M, and A is the m); rs2305479 (C is the M, and T is the m); and rs11078928 (T is the M, and C is the m). Of note, variants are ordered by mapped position (lowest to highest) in reference genome hg38. However, the GSDMB (gasdermin-B) gene is transcribed from the negative strand. Therefore, rs11078928 is 5′ to the rs16965388 transcribed gene. The GSDMB nucleotide polymorphisms are reported according to the positive (nontranscribed) strand.
ORs are in comparison with the reference haplotype (G-G-C-T).