Genetic analysis of inflammatory proteins following BCG vaccination in Danish children

The Bacillus Calmette-Guérin (BCG) vaccine, primarily designed for tuberculosis, exerts non-specific immunological effects that vary considerably among children. Limited knowledge exists regarding genetic variants that can impact immune responses post-vaccination. Understanding the genetic factors influencing the immune response in children following BCG vaccination is crucial for optimizing vaccine strategies. Genome-wide pQTL mapping of 65 circulating inflammatory proteins profiled at Month 13 uncovered 11 independent genome-wide significant loci. Following pQTL mapping in BCG-unvaccinated children, whose mean age was not significantly different from that of BCG-vaccinated children, a P-value lookup complemented with statistical colocalization and interaction analyses identified four pQTLs (rs10217747: CXCL11, rs13187850: CD6, rs56283092: LAP-TGF-beta 1, and rs11708321: CDCP1) showing evidence of genotype-by-BCG interactions and larger effect estimates in the BCG group. These variants have previously been associated with inflammatory and autoimmune traits. Genetic analysis of in vitro cytokine production capacity after BCG vaccination identified nominal associations mainly at Month 13 rather than Day 4 or Month 3. These findings enhance our understanding of immune responses to vaccination in children but, given the exploratory genome-wide approach, should be considered hypothesis-generating and require further validation.