Ancient DNA suggests anaemia and low bone mineral density as the cause for porotic hyperostosis in ancient individuals

Abstract

Porotic hyperostosis (PH) is a disease that had high prevalence during the Neolithic. Several hypotheses have been suggested to explain the origin of the disease, such as an iron deficiency diet, low B12 intake, malaria caused by Plasmodium spp., low haemoglobin levels or low vitamin D levels. None of these hypotheses have been tested genetically. Here, I calculated different genetic scores to test each hypothesis. Additionally, I calculated a genetic score of bone mineral density as it is a phenotype that seems to be selected in ancient Europeans. I apply these genetic scores on 80 ancient samples, 33 with diagnosed PH. The results seem to suggest anaemia and low bone mineral density as the main cause for this disease. Additionally, Neolithic individuals show the lowest genetic risk score for bone mineral density of all other periods tested here, which may explain the highest prevalence of the porotic hyperostosis during this age.

Ancient DNA supports that the evolution of Skin Tone in East Asians intensified after their split with Native Americans

“…sun radiation at which each population is exposed or geographical variables such as latitude or longitude). However, there is also the possibility that differences in the allele frequency among individuals are caused by differences in their ancestry (1, 14). For example, if individuals with higher values for a less pigmented skin genetic score belong to a different population than individuals with lower values they will be sharing different alleles, including those associated with skin tone.…”

“…Polygenic Risk Scores are applied to study phenotypes that are influenced by multiple genomic variants (14-18). In humans, examples of these phenotypes are skin pigmentation, bone mineral density or height.…”

“…A genetic risk score can be obtained by summing all the alleles related to a particular phenotype (15) associating a value to the likelihood to develop a particular phenotype (for example, developing a higher or lower bone mineral density, or to develop a darker or a pale pigmentation skin). Polygenic risk scores have been applied several times in ancient DNA studies, for example, to study the height in ancient Europeans (16, 17) to study the genomic variants associated with a bone disease (14), to study the evolution of attention/deficit hyperactivity disorder in Neanderthals and ancient Europeans (18) and, as here, the likelihood to develop a particular skin pigmentation, but in Europeans (1). In this study, the genetic risk score was calculated by summing in each individual all the alleles related to skin pigmentation multiplied by their betta value (a value that measures the intensity that the alleles are related to skin pigmentation) See Supplementary Table 1 ).…”

“…The resulting VCF files were phased and imputed with Beagle 5.4 (version 22Jul22.46e). To phased them I used 1000 genome phase 3, downloaded as reference panels from https://bochet.gcc.biostat.washington.edu/beagle/1000_Genomes_phase3_v5a/b37.bref3/ and GRCh37 genetic maps from https://bochet.gcc.biostat.washington.edu/beagle/genetic_maps/ Polygenic Risk Score estimation Polygenic Risk Scores are applied to study phenotypes that are influenced by multiple genomic variants (14)(15)(16)(17)(18). In humans, examples of these phenotypes are skin pigmentation, bone mineral density or height.…”