Biology subjects

Jylhävä, J.

Publications and source records attributed to Jylhävä, J..

3 recordsLinked to original sources

bioRxiv2022

Methylation status of VTRNA2-1/nc886 is stable across human populations, monozygotic twin pairs and in majority of somatic tissues

Aims and methodsOur aim was to characterise the methylation level of a polymorphically imprinted gene, VTRNA2-1/nc886, in human populations and somatic tissues. We utilised 48 datasets, consisting of >30 different tissues and >30 000 individuals. ResultsWe show that the nc886 methylation status is associated with twin status and ethnic background, but the variation between populations is limited. Monozygotic twin pairs present concordant methylation, while [~]30% of dizygotic twin pairs present discordant methylation in the nc886 locus. The methylation levels of nc886 are uniform across somatic tissues, except in cerebellum and skeletal muscle. ConclusionWe hypothesize that the nc886 imprint is established in the oocyte and that after implantation, the methylation status is stable, excluding a few specific tissues.

molecular biology↗

bioRxiv2019

Comprehensive longitudinal study of epigenetic mutations in aging

BackgroundThe role of DNA methylation in aging has been widely studied. However, epigenetic mutations, here defined as aberrant methylation levels compared to the distribution in a population, are less understood. Hence, we investigated longitudinal accumulation of epigenetic mutations, using 994 blood samples collected at up to five time points from 375 individuals in old ages.\n\nResultsWe verified earlier cross-sectional evidence on the increase of epigenetic mutations with age, and identified important contributing factors including sex, CD19+ B cells, genetic background, cancer diagnosis and technical artifacts. We further classified epigenetic mutations into High/Low Methylation Outliers (HMO/LMO) according to their changes in methylation, and specifically studied methylation sites (CpGs) that were prone to mutate (frequently mutated CpGs). We validated four epigenetically mutated CpGs using pyrosequencing in 93 samples. Furthermore, by using twins, we concluded that the age-related accumulation of epigenetic mutations was not related to genetic factors, hence driven by stochastic or environmental effects.\n\nConclusionsHere we conducted a comprehensive study of epigenetic mutation and highlighted its important role in aging process and cancer development.

genetics↗

bioRxiv2018

The frailty index is a predictor of cause-specific mortality independent of familial effects from midlife onwards

BackgroundFrailty index (FI) is a well-established predictor of all-cause mortality, but less is known for cause-specific mortality and whether familial effects influence the associations. Furthermore, the population mortality impact of frailty remains understudied.\n\nObjectivesTo estimate the predictive value of frailty for all-cause and cause-specific mortality, and to test whether the associations are time-dependent. We also assessed the proportion of deaths that are attributable to increased levels of frailty.\n\nMethodsWe analyzed 42,953 participants from the Screening Across the Lifespan Twin Study (aged 41-95 years at baseline) with up to 20-years mortality follow-up. The FI was constructed using 44 health-related items. Deaths due to cardiovascular disease (CVD), respiratory-related causes and cancer were considered in the cause-specific analysis. Generalized survival models were used in the analysis.\n\nResultsIncreased FI was associated with higher risks of all-cause, CVD, and respiratory-related mortality. No significant associations were observed for cancer mortality. No attenuation of the mortality associations was found in unrelated individuals when adjusting for familial effects in twin pairs. The associations were time-dependent with relatively greater effects observed in younger ages. The proportion of deaths attributable to FI levels >0.10 were 13.0% of all-cause deaths, 14.7% of CVD deaths and 12.5% of respiratory-related deaths in men, and 12.2% of all-cause deaths, 9.9% of CVD deaths and 21.9% of respiratory-related deaths in women.\n\nConclusionsIncreased FI predicts higher risks of all-cause, CVD, and respiratory-related mortality independent of familial effects. Increased FI levels have a significant population mortality impact in both men and women.

epidemiology↗