Disease incidences increase with age, but the molecular characteristics of ageing that lead to increased disease susceptibility remain inadequately understood. Here we perform a whole-blood gene expression meta-analysis in 14,983 individuals of European ancestry (including replication) and identify 1,497 genes that are differentially expressed with chronological age. The age-associated genes do not harbor more age-associated CpG-methylation sites than other genes, but are instead enriched for the presence of potentially functional CpG-methylation sites in enhancer and insulator regions that associate with both chronological age and gene expression levels. We further used the gene expression profiles to calculate the ‘transcriptomic age' of an individual, and show that differences between transcriptomic age and chronological age are associated with biological features linked to ageing, such as blood pressure, cholesterol levels, fasting glucose, and body mass index. The transcriptomic prediction model adds biological relevance and complements existing epigenetic prediction models, and can be used by others to calculate transcriptomic age in external cohorts.

No abstract

Nematode parasites show a characteristic aggregated distribution among hosts. This observation has important implications for pathogenesis, immunology, and control of these infections, but the relative roles of environment and genetics in determining these patterns have remained uncertain. This paper presents the results of the first genome scan for susceptibility to infection with roundworm (Ascaris lumbricoides). Data on 375 genetic markers were generated for each of 444 members of a genetically isolated Nepalese population, the Jirels. Ascaris worm burden as assessed by egg counts was measured in these same individuals by using the Kato Katz thick smear method. The extensive genealogical data available for the population allowed assignment of all 444 individuals to a single pedigree that contained 6,209 pairs of relatives that were informative for genetic analysis. A variance components linkage analysis resulted in the unequivocal localization of two genes (one on chromosome 1 and another on chromosome 13) with clear, significant effects on susceptibility to Ascaris infection. This is the first evidence that individual quantitative trait loci influence variation in Ascaris burden in humans.

Knowledge of cross-transmission and hybridization between parasites of humans and reservoir hosts is critical for understanding the evolution of the parasite and for implementing control programmes. There is now a consensus that populations of pig and human Ascaris (roundworms) show significant genetic subdivision. However, it is unclear whether this has resulted from a single or multiple host shift(s). Furthermore, previous molecular data have not been sufficient to determine whether sympatric populations of human and pig Ascaris can exchange genes. To disentangle patterns of host colonization and hybridization, we used 23 microsatellite loci to conduct Bayesian clustering analyses of individual worms collected from pigs and humans. We observed strong differentiation between populations which was primarily driven by geography, with secondary differentiation resulting from host affiliation within locations. This pattern is consistent with multiple host colonization events. However, there is low support for the short internal branches of the dendrograms. In part, the relationships among clusters may result from current hybridization among sympatric human and pig roundworms. Indeed, congruence in three Bayesian methods indicated that 4 and 7% of roundworms sampled from Guatemala and China, respectively, were hybrids. These results indicate that there is contemporary cross-transmission between populations of human and pig Ascaris.