Three interesting studies of genetic variation

Meiosis errors, Epstein-Barr virus, and lifespan

I haven’t had much time for blogging these days, but I wanted to highlight three cool studies that came out recently, studying the genetics of meiosis, Epstein-Barr virus, and lifespan.

Genetics of meiosis fidelity

Common variation in meiosis genes shapes human recombination and aneuploidy (Carioscia et al., Nature 2026). This study looked at data from an embryo testing company, Natera,¹ which used SNP microarrays to determine embryo genotype and chromosome copy number. The researchers also obtained genotypes of the parents. This gave a sample size of 22,850 biological mothers and 139,416 embryos. Getting this data must have been a bureaucratic nightmare!

Fig. 1 from (Carioscia et al., Nature 2026) (CC-BY). The biggest factor for aneuploidy is maternal age, but genetics also have a role!

With the ability to examine genotypes of both parents and embryos, the researchers identified variants in meiosis-associated genes which impact the number of crossovers during meiosis and the risk of aneuploidy. Aneuploid embryos tended to have fewer crossovers, which makes sense given that a lower crossover rate would increase the risk of having zero crossovers (in which case the chromosomes wouldn’t stay together). Furthermore, women with high risk of having aneuploid embryos also had a shorter reproductive lifespan (later menarche and earlier menopause).

It would be quite interesting to see if these results replicate in Ovelle’s in vitro meiosis induction system.

Genetics of Epstein-Barr virus infection

Population-scale sequencing resolves determinants of persistent EBV DNA
I’ve been interested in Epstein-Barr virus (EBV) for a while due to its prevalence and ability to cause a wide variety of problems (autoimmune diseases, cancer, etc.)

For historical reasons,² the EBV genome was included in the GRCh38 human genome reference assembly. Most researchers ignore this, but Nyeo et al. looked at EBV read counts in UK Biobank whole genome sequencing data, which comes from blood samples. They found that about 10% of individuals had a high burden of EBV DNA in their blood. Over 90% of the UK Biobank population is positive for EBV, so the people with a lot of EBV DNA represent those whose immune systems struggle to control the infection.

The genetics of persistent EBV DNA were strongly associated with the immune system. There were several significant genetic variants across the genome, but the most important were at the HLA locus (which will be no surprise to any immunologist). Understanding HLA interactions with EBV may help with vaccine development, and this paper makes a big contribution.

The researchers also looked at genetic variation within the EBV genome, but didn’t find any significant effects on pathogenesis (this was strong evidence against the results of several previous smaller studies).

Genetics of lifespan

Heritability of intrinsic human life span is about 50% when confounding factors are addressed

Human lifespan, like other complex traits, is heritable to at least some extent. Readers may recall that heritability of a trait is the proportion of total variance explained by genetic variance (as opposed to non-genetic variance).

Many previous studies found a rather low heritability for lifespan (about 20-25%). But it turns out that this is because they examined cohorts who were born from 1870-1920, when non-genetic variance of lifespan was much higher than it is today. This study (Shenhar et al. 2026) examined three cohorts of Scandinavian twins and one cohort of American centenarian-sibling pairs, and analyzed extrinsic (accident, homicide, infectious disease) vs intrinsic mortality.

Fig. 1 of Shenhar et al. 2026 (CC-BY)

The result is somewhat of a tautology: when ignoring many sources of environmental variance (extrinsic mortality), the heritability of lifespan increases to 50-55%. But this is still interesting, because extrinsic mortality is much lower today than it was 100 years ago, so the higher estimate of heritability is more relevant.

Hopefully extrinsic mortality will remain low across the world in years to come!

1. Natera recently discontinued PGT-A testing; I’m not sure why

2. Early human genome sequencing often used cell lines that were positive for EBV, and researchers wanted to exclude EBV reads from aligning to the true human genome by adding a decoy EBV sequence.