Breakdown - How Your Ancestry Affects You Today ( Pankratov et al 2023)

Paper: 'Ancestral genetic components are consistently associated with the complex trait landscape in European biobanks'

An interesting preprint was circulated around Twitter/X recently, one which might have some fascinating revelations about how your European ancestry affects you biologically today. As many people know, especially long time readers, our understanding of genetics has advanced to the point where we can confidently talk about the main demographic changes which produced modern Europeans. There are three main ancestral components - firstly the post Ice Age hunter-gatherers of the Mesolithic, generally referred to as Western Hunter-Gatherers (WHGs); secondly the Neolithic farming populations which came from Anatolia, often called Early European Farmers (EEFs), and finally the steppe nomads who moved into Europe at the beginning of the Bronze Age, usually called Yamnaya or Western Steppe Herders (WSHs).

These three groups, in various proportions, account for the overwhelming majority of modern European heritage. Since this has been established, researchers are beginning to tease apart what different qualities and traits these different populations brought to the table. One way to do this is called a ‘Genome Wide Association Study’. Simply put, this type of study takes a large number of people who have had their genomes sequenced, then look for a phenotypic trait (say, height, or eye colour) and then see what particular genetic variants are associated with that trait.

In a joint study from researchers based in Scotland, Italy and Estonia - a Genome Wide Association Study was performed using 35,000 individuals from the Estonian Biobank, and 50,000 UK Biobank donors. The rationale being that levels of WHG/EEF/WSH vary from east to west/north to south across Europe. They looked at 53 traits, and used the different ancestral proportions compared to the genetic markers, providing a wide survey of many biological traits and how they are associated with types of ancestry.

You can see all the traits listed on the left here, in order of whether they showed any correlation with ancestry in the different populations. Towards the bottom there is no divergence at all.

The largest signals found in our analysis are divergences in resting heart rate, platelet count and monocyte percentages in blood which increase together with WHG ancestry similarity, see Figure 2A. As shown by our simulations, adaptation might not be necessary to observe such divergence. Nevertheless, given health-relevant changes in platelet count and heart rate variability during winter, coupled with the complex heart rate reactions to cold exposure, it is tempting to speculate about an adaptation to colder climates that WHG suffered when colonizing Europe soon after the last glacial maximum (after 17kya). A similar pattern of divergence can be observed for BMI, hemoglobin concentration, eosinophil blood concentrations and heel bone mineral density. Interestingly, some of these traits such as platelet count and BMI were found to be selected for lower levels during the early Neolithic thus supporting the idea of higher values being WHG-specific and possibly maladaptive in later periods, in favor of more recent incoming genetic components. We replicate known signals of genetic divergence across ancestries for anthropometric and pigmentation traits, most notably an association of Yamnaya ancestry with tall stature and large waist, but also with darker hair and skin pigmentation, surprisingly coupled with poor ease of tanning. These results corroborate the hypothesis that pigmentation decrease in Europe is rather due to post-admixture selection rather than impact of incoming Yamnaya migrations during the Bronze Age. Some red blood cell properties are also divergent, with lower corpuscular volume but higher cell count associated with Yamnaya ancestry, while the opposite is true for Anatolia_N ancestry. These properties are important readouts for B12, folic acid and moreover iron intake, potentially indicating adaptations to pastoralist or farming diets. In this and other cases consistent with findings in EstBB such as blood cholesterol levels, caffeine intake, but also previously mentioned traits (e.g. monocyte percentage, pigmentation), two ancestries are both highly significant for opposite trait values.

There is a lot to unpack here. So having performed the tests on the sample populations, the returned results showed that many traits had no correlation with ancestry, such as ‘age of first intercourse’, ‘grip strength’ and ‘depression’. But some did, and the divergence between them was significant. As the highlighted text shows, a lot of cardiovascular and metabolic traits do show WHGs as outliers, perhaps cold adapted? The authors speculate that some of these traits became maladaptive when confronted with EEF admixture, who presumably were far less cold adapted. That the steppe herders were bigger is no surprise based on skeletal evidence, but their poor tanning skills and slightly darker skin than expected suggests that skin pigmentation, vitamin D and sunlight exposure was a complex genetic landscape until relatively recently? Finally the diet and metabolic traits of the EEF, especially iron metabolism, should also be no surprise. If anyone has read my piece on the Irish famine and haemochromatosis, you’ll be familiar with the point that agricultural diets were a threshold in human metabolism vis-à-vis iron and anemia.

These were the strongest correlations, some weaker ones included:

One last notable example of such a pattern is the frequency of asthma diagnoses, which appear to be positively associated with WHG ancestry and negatively with Yamnaya. Interestingly, the Yamnaya genetic component is also weakly associated with lower indicators of pulmonary function, such as FVC and FEV1. In addition, we find weaker but significant associations of Anatolia_N ancestry with hypermetropia, already suggestive in EstBB, and Yamnaya ancestry with lower blood pressure (both systolic and diastolic) and consequent reduced exposition to hypertension, which was not evident in EstBB . Other weakly divergent traits appreciable in Figure 2A include smoking status, age at menarche and hypothyroidism

How much these should be taken as fact or just noise is uncertain. Certainly something like age of menarche has multiple other factors, significantly diet and levels of physical activity. But still, asthma with WHGs and lower blood pressure for WSHs is an interesting result all the same.

Skin colour and height have been closely followed since the main 2015 genetic papers. But now we see other big divergences between populations, in particular heart rate, inflammatory/immune traits like platelet count and white blood cells, and bone mineral density. Whether these traits were positively selected for to begin with, or a function of genetic drift, remains to be seen. But clearly we are just scratching the surface of how much of a biological shift both the advent of agriculture and the advance of the steppe people was for Europe.