Discussion
Our results suggest the effect of RhD genotype-sex interaction on
physical health. Generally, Rh-positive homozygotic women reported worse
physical health than both Rh-negative and heterozygotic women, while
Rh-negative men reported worse physical health than Rh-positive
homozygotic and heterozygotic men. Similar yet nonsignificant trends in
the same direction are present when the mental health of subjects with
Rh-negative and Rh-positive phenotype is compared. Better health of
heterozygotes than homozygotes was expected a priori based on the
theory and already published data (Flegr,
Toman, et al., 2020). Therefore, more sensitive one-sided tests should
be used in the confirmatory part of the study. Result of this test, the
effect of Rh-sex interaction on physical health, remained significant (p
= 0.019) after the correction for multiple (here two) tests.
Detailed analyses showed that Rh-positive homozygote women reported
being more often tired, more often spending more than seven days in a
hospital in the past 5 years, having more frequent chronic health
problems, physical pain, headaches, migraines, orthopedic problems,
neurological problems, attending medical doctors more often, taking more
antibiotics in the last year, and having “other mental health
problems” more often than Rh-negative homozygote women. In contrast,
Rh-positive homozygote men reported better physical condition at the
time of blood sample-taking, a higher life expectancy, and less frequent
common infectious diseases than Rh-negative homozygote men. The number
of significant effects was lower in men than in women, probably because
of the much lower number of men than women in our sample (86 vs 178),
however, the effects were usually stronger than in women. For example, a
partial Kendall’s Tau -0.429 for common infectious diseases was
equivalent to R2 0.49, which means that Rh genotype
was responsible for nearly 50% of the variability in the frequencies of
common infectious diseases in the sample of male Rh-positive and
negative homozygotes.
A comparison of female Rh-positive homozygotes and heterozygotes showed
that heterozygotes had fewer headaches, skin disorders, orthopedic
disorders, neurological disorders, suffered less physical pains, less
chronic physical problems, are less frequently tired, and feel in better
mental health conditions usually, as well as at the time of blood
sample-taking. The same comparison for male homozygotes and
heterozygotes showed that heterozygotes had had fewer acute illnesses in
the past 6 months, feel usually in better mental conditions, and
especially feel less depressed. At the same time, heterozygotes reported
to be treated for chronic problems more often – which corresponded with
taking more prescribed drugs at the time of blood sample-taking.
Heterozygotic men reported less frequent acute disorders, especially
common infectious diseases, and less frequent or less serious depression
than Rh-negative men. Paradoxically, heterozygotic women reported more
frequent headaches, consuming more antibiotics, and staying for more
than one week in the hospital more often than Rh-negative women. A
higher frequency of headaches in (healthier) heterozygotes was already
described in the previous study (Flegr,
Toman, et al., 2020).
A comparison of women with Rh-positive and Rh-negative phenotype showed
worse health of the former. Rh-positive women reported more chronic
problems, more headaches, migraines, orthopedic disorders, more frequent
use of antibiotics in the past year, more frequently spending at least
seven days in a hospital in the past five years, and more intensive
“other” mental health problems (other than depression, anxiousness,
phobias). Rh-positive men reported longer life expectancy, less frequent
chronic physical health problems, and less frequent common infectious
diseases. In fact, Rh-positive men scored non-significantly better in
nearly all other health-related variables (except frequency of
hospitalization) but most of these (sometimes relatively strong)
associations were non-significant because of the low number of male
participants in the study.
Present results can be compared with those of the recent study based on
data from 2,539 respondents of an electronic questionnaire (23% Rh
negative) (Flegr, Toman, et al., 2020).
In this study, a subpopulation of Rh-positive heterozygotes was
identified based on their Rh-phenotype (positive) and Rh-phenotype of
their biological parents (either father or mother Rh-negative). This
design did not allow comparing Rh-positive homozygotes with the other
two groups because part of heterozygotes did not report an Rh-negative
parent and these subjects finished in the same group as homozygotes.
Moreover, the spectrum of health-related variables under the
above-mentioned study was different and far narrower in comparison with
the present study.
Results of the internet study (Flegr,
Toman, et al., 2020) showed that heterozygotes have better health than
both types of homozygotes. In contrast to the present study, subjects
with Rh-positive phenotype (especially men) expressed better health than
those with Rh-negative phenotype, which is in agreement with the results
of other studies. The internet study found a stronger effect of Rh
phenotype on mental health than on physical health; in the current
study, the effect of genotype on mental health was not significant.
Besides, the previous study observed worse physical health in
Rh-positive than in Rh-negative homozygotes both in men and women (not
only in women as it was in the current study). Nevertheless, it must be
remembered that the current study was performed on just 86 men (23
Rh-positive and 23 negative homozygotes) compared to 502 men in the
previous study. Therefore, the absence of certain significant effects
could be the result of the smaller population sample analyzed in the
current study.
Another recent internet study performed on a sample of 5,527
participants (24% Rh negative) compared only the physical and mental
health of subjects with Rh-positive and Rh-negative phenotype
(Flegr, Kuba, & Kopecký, 2020). This
internet study found worse health in Rh-positive women and better health
in Rh-positive men in comparison to corresponding Rh-negative controls.
All available data about the performance of Rh-positive homozygotes and
heterozygotes (Flegr et al., 2008;
Flegr, Toman, et al., 2020;
Novotná et al., 2008) and the present
study therefore suggest that Rh-positive heterozygotes have better and
Rh-positive homozygotes have worse heath than Rh-negative subjects.
Consequently, it could be argued that the results of a study depend on
the heterozygote-to-homozygote ratio among Rh-positive subjects. This
ratio increases with the increasing prevalence of Rh-minus allele in the
population under study, which depends not only on its prevalence in a
general population but probably also on the auto-selection of the
participants of the study – see the over-representation of Rh-negative
subjects in the studies discussed below.
Another biological variable that should be taken into consideration is
the prevalence of latent toxoplasmosis in studied population sample.
This prevalence varies approximately from 10 to 70% among various
countries, depending on environmental conditions (especially moisture),
eating and other cultural habits, and hygienic standards
(Pappas et al., 2009;
Tenter et al., 2000). It also strongly
varies in relation to urbanization and increases with the age of
subjects (Flegr, 2017;
Kolbeková, Kourbatova, Novotná, Kodym, &
Flegr, 2007). It has been known for a long time that the effects of
Rh-genotype are modulated by toxoplasmosis
(Flegr et al., 2008;
Novotná et al., 2008). For example, amongToxoplasma -free subjects, those who are Rh-negative have
extremely good reaction times. However, after Toxoplasmainfection, the reaction times of Rh-negatives strongly deteriorate. This
results in the observation that Rh-negative Toxoplasma -infected
individuals express the worst reaction times from all subjects. In
contrast with that, the reaction times of Rh-positive homozygotes impair
only slightly while the reaction times of Rh-positive heterozygotes
improve. It has been suggested that this might show that the natural
status of our relatively recent ancestors was actually beingToxoplasma -infected with our physiology tuned up to this status
(Flegr, Toman, et al., 2020). If we
continue in this line of thinking, the spreading of the allele for
Rh-negativity in Europe could have been related to the relative scarcity
of toxoplasmosis in Europe before the advent of the domestic cat – the
only important definitive host of Toxoplasma in Holocene Europe
(Novotná et al., 2008;
Torrey & Yolken, 1995). It is therefore
desirable to control or this variable in future studies. The prevalence
of latent toxoplasmosis in Czech residents of middle age is relatively
high, especially in women (Flegr, 2017).
The presence of about one-third of Toxoplasma -infected subjects
therefore might explain some heterogeneity in the distribution of the
health problems score observed in our data (Fig. 1). In future
(large-scale) studies, analyses should be done separately forToxoplasma -free and Toxoplasma -infected subjects.