TABLE 5.
Studies investigating for causal association between biochemical factors and asthma using MR
| First author, year | Method | Cases No. | Asthma/allergy | Quality score |
|---|---|---|---|---|
| Raita et al. (2021) 44 | IVW meta‐analysis method | 394,256 subjects of European ancestry | OR per one SD increment in inverse‐rank normalized soluble IL‐6R level 1.02 (95% CI: 1.01–1.03) | 12 |
| Lyons et al. (2019) 50 | IVW | 534 EPGA cases and 6688 controls | Finding a causal effect of eosinophil count on EGPA risk, p < 7.7 × 10−12 | 12 |
| Groot et al. (2020) 53 | PheWAS and Wald estimates | UK biobank: 422,408 unrelated individuals | Wald beta effect estimate for atopy including asthma associated with genetically determined higher levels of clostridium cluster IV ‐0.54 (SE: 0.04), (RR: 0.58 (95% CI: 0.54–0.63)), p = 1.45*10−37 | 11 |
| Amini et al. (2018) 51 | Two‐stage, least square (2SLS) | 13,301 in Lifeline cohort, 967 asthma cases | No significant association for eosinophil count and asthma risk | 10 |
| Zhu et al. (2019) 47 | Generalized summary data‐based Mendelian randomization | UK biobank and Psychiatric genomics consortium: 347,481 European controls and 46,889 asthma cases | Beta effect estimate for MR for asthma associated with MDD: β = 0.21, (SE = 0.049), p = 1.80*10−5 and associated with ADHD: β = 0.054, (SE = 0.026), p = 0.036 | 9 |
| Mulugeta et al. (2020) 46 | PheWAS and random effects IVW | UK biobank: 337,536 white British | OR for asthma associated with MDD 1.23 (95% CI: 1.06–1.44), and OR for painful respiration 1.28 (95% CI: 1.14–1.44) | 9 |
| Rosa et al. (2019) 45 | PheWAS MR and two sample MR IVW | 180,129 asthma cases and 180,709 controls of European ancestry | OR for asthma in causal inference with sIL‐6R 1.03 (95% CI: 1.02–1.04), p = 5.62*10−8 | 9 |
| Valette et al. 49 | IVW | 56,167 asthma cases and 352,255 controls from UKB | Identified 50 blood expressed genes to be causally associated to risk of asthma including MHC, FADS1 and SMAD3 | 9 |
| Huang et al. (2020) 48 | Two‐sample MR Weighted mode | Australian birth cohort (CAS) 234 individuals followed from birth to 10 years | In resting T cells, log odds decrease per SD increase in BTN3A2 for asthma = −0.056. For childhood asthma: −0.047. For adult‐onset asthma: −0.039. For allergic rhinitis: −0.044 | 9 |
| McGowan et al. (2019) 43 | Wald ratio | UK biobank: 38,791 asthma cases and 297,991 controls | Beta effect estimate for asthma: sIL‐6R: 0.0103 (SE: 0.0027), p = 0.0001, IL‐1R: −0.0035 (SE: 0.0018), p = 0.0451 | 7 |
| Folkersen et al. (2020) 42 | IV Wald ratio estimate | Total of up to 21,758 individuals primary European; average per‐protein sample size was 17,747 | Beta for asthma per SD protein for cis‐SNPs for CASP‐8: 0.32 (95%CI: 0.14–0.51), p = 6.1e−04, IL‐6RA: 0.07 (95% CI: 0.04–0.09), p = 6.3e−07, ST2: −0.18 (95% CI: −0.22 to −0.14), p = 4.0e−19 | 7 |
| Arathimos et al. (2017) 52 | Wald ratio | ALSPAC and GABRIEL consortium | No significant evidence for causal effects of increased DNA methylation on asthma. | 6 |
Abbreviations: ADHD, Attention deficit hyperactivity disorder; BTN3A2, Butyrophilin Subfamily 3 Member A2; CAS, Childhood Asthma Study; CASP‐8, Caspase eight; CI, Confidence interval; EGG, Early Growth Genetics; FADS1, Fatty acid desaturase one; GERA, Genetic Epidemiology Research on Aging; IL‐1R, Interleukin 1 receptor; IL‐6RA, Interleukin 6 receptor alpha; IVW, Inverse variance Weighting; MDD, Major Depressive Disorder; MHC, Major histocompatibility complex; MR, Mendelian Randomization; OR, Odds ratio; SD, Standard deviation; SE, Standard Error; sIL‐6R, Soluble Interleukin 6 receptor; SMAD3, SMAD family member 3; ST2, Suppression of tumorigenicity two; UKB, United Kingdom biobank.