The effects of RhD blood group genotype on physical and mental health: A preregistered cross-sectional study - data

Data for the paper The effects of RhD blood group genotype on physical and mental health: A preregistered cross-sectional studyBackground The stable coexistence of RhD-positive and RhD-negative subjects in a population is an evolutionary conundrum because carriers of the less numerous allele as a rule suffer from lower fecundity due to frequent haemolytic anaemia of (RhD-positive) newborns born to RhD-negative women. One explanation of continued stable existence of RhD polymorphism is based on the idea of selection in favour of heterozygotes. In the past eleven years, numerous studies demonstrated that RhD-positive subjects score better in psychomotor tests and health-related variables than RhD-negative homozygotes. Nevertheless, evidence of better health and performance of heterozygotes is scarce and merely indirect. Methods In this preregistered study, we compared the physical and mental health of 2,539 subjects whose RhD genotype could be estimated based on their and their parents’ RhD phenotype. We also compared the prevalence of 23 mental health disorders in RhD-negative and RhD-positive subjects. We confirmed that RhD-negative homozygotes are in worse physical and mental health than subjects with RhD-positive phenotype and that RhD-positive heterozygotes enjoy better health than a mixed population of all other genotypes. RhD-negative subjects are more frequently diagnosed with obsessive-compulsive disorder (OR=2.25, C.I.95 = 1.08–4.54) and with epilepsy (OR=2.57, C.I.95 = 1.10–5.82), whereby both values remained significant after correction for multiple tests. Results For the first time, we demonstrated that RhD-positive homozygotes suffer from worse health than RhD-negative homozygotes, which strongly supports the heterozygote advantage hypothesis. When subjects with RhD-negative and RhD-positive phenotype are compared, the worse health of RhD-positive homozygotes could outweigh the better health of RhD-positive heterozygotes especially in countries with a low frequency of alleles for RhD-negativity, where most RhD positive individuals are homozygotes. This suggests that the effects of RhD genotypes, not phenotypes, should be compared in future studies.