Genome-wide association study reveals the unique genetic structure of active blood donors

The healthy donor effect (HDE) refers to the observed lower mortality rate among blood donors compared to the general population. While membership biases such as HDE arise due to healthier individuals being more likely to participate, the extent to which it is influenced by genetic differences remains largely unclear. To elucidate the genetic basis of HDE, we conducted a genome-wide association study (GWAS) involving 53,688 active blood donors with extensive donation histories and 228,060 controls from biobank cohorts within the FinnGen project. Our results identified 2,973 genome-wide significant loci associated with repeated blood donation and impacting several health-related endpoints. Importantly, significant variants related not only to blood groups but also influenced the predisposition to somatic and mental diseases, suggesting that HDE is not solely tied to blood donation eligibility criteria. In conclusion, in this work we show that HDE is partially explained by genetic factors affecting various disease categories.