Trans-ethnic analysis in over 780,000 individuals yields new insights into the genetic etiology of allergic diseases

Ever-increasing studies revealed an etiological association between peripheral blood markers and allergic diseases, yet the debate on causality persists. Here, we performed Mendelian randomization (MR) analyses over 780,000 individuals to explore the generalizability and heterogeneity of causalities among diverse allergic diseases and ethnicities. MR analyses from three nationwide biobanks identified seven shared heritable factors on broad allergic disease phenotype in diverse ethnicities, three of which are newly discovered, and were further corroborated by our observational studies in China andUnited States (US). The causalities of part of these factors on specific allergic diseases are heterogeneous, reflecting the etiological discrepancy among different allergic diseases. Moreover, we identified 11 ethnic-specific causal factors, indicating the necessity of considering patients’ ethnic backgrounds before formulating prevention strategies. Our results support the causalities of 22 factors on allergic diseases, providing valuable insights for the assessment of allergic risks and the design of universal and personalized interventions.