A Risk Factor Atlas for Allergy-Related Airway Diseases: Evidence From Multi-Biobank Genetic Study

Purpose: Understanding factors contributing to allergy-related airway diseases (AADs).Methods: We conducted a meta-analysis of Mendelian randomization (MR) estimates from multi-biobank to investigate the effects of 83 common factors on asthma, allergic rhinitis (AR), chronic rhinosinusitis (CRS), and nasal polyps (NPs).Data for AADs were obtained from multiple independent populations including FinnGen, UK Biobank and large consortia (asthma, 137,498 cases and 1,009,466 controls; AR, 51,712 cases and 592,784 controls; CRS, 24,688 cases and 760,073 controls; and NP, 11,796 cases and 760,075 controls).The metaanalyses combining the above multi-biobank MR results were employed as our main results.Results: Genetically proxied social isolation, smoking time and frequency, sedentary time, global and central obesity, C-reactive protein (CRP), insomnia, major depressive disorder (MDD), anxiety, attention deficit hyperactivity disorder, neuroticism, posttraumatic stress disorder (PTSD), rheumatoid arthritis (RA), atopic dermatitis (AD), type 1 diabetes (T1D), gastroesophageal reflux disease (GERD), childhood obesity, early menarche, smoking around birth, and childhood maltreatment could increase the risk of asthma.Education, higher income, cheese intake, sleep duration, high density lipoprotein cholesterol, forced expiratory volume in 1 second/forced vital capacity, well-being and ulcerative colitis were associated with a decreased risk of asthma.Social isolation, CRP, Crohn's disease, GERD, insomnia, MDD, neuroticism and AD could increase the risk of AR, whereas well-being could decrease the risk of AR.Sedentary time, MDD, anxiety, PTSD, opioid use disorder, RA, AD, T1D, hypothyroidism, and GERD could increase the risk of CRS, whereas coffee intake, apolipoprotein A1, and well-being were associated with a decreased risk of CRS.Smoking duration, RA, AD and T1D could increase the risk of NP, whereas fresh fruit intake could decrease the risk of NP.Conclusions: This study offers potential causal evidence for AAD risk factors and provides actionable targets for primary prevention.