A5043098809- Epigenetics and DNA Methylation
- Birth, Development, and Health
- Genetic Associations and Epidemiology
- Genetic Syndromes and Imprinting
- Adipose Tissue and Metabolism
- Health, Environment, Cognitive Aging
- Genetics and Neurodevelopmental Disorders
- Synthesis and Biological Evaluation
- Genetic factors in colorectal cancer
- Childhood Cancer Survivors' Quality of Life
- Cancer-related gene regulation
- RNA modifications and cancer
- Diet and metabolism studies
- Identity, Memory, and Therapy
- Cancer Diagnosis and Treatment
- Adolescent and Pediatric Healthcare
- Smoking Behavior and Cessation
- Bioinformatics and Genomic Networks
- Prenatal Screening and Diagnostics
- Nutritional Studies and Diet
- Cannabis and Cannabinoid Research
- Metabolomics and Mass Spectrometry Studies
- Cancer-related molecular mechanisms research
- Nicotinic Acetylcholine Receptors Study
- Nutrition, Genetics, and Disease
University of Helsinki
2016-2025
Institute for Molecular Medicine Finland
2017-2025
Minerva Foundation
2022-2025
Finland University
2017-2024
ORCID
2021
Duke University
2021
National Heart Lung and Blood Institute
2018
University of Mississippi Medical Center
2018
Framingham Heart Study
2018
University Medical Center Groningen
2018
Mounting evidence from both animal and human studies suggests that the epigenome is in constant drift over life course response to stochastic environmental factors. In humans, this has been highlighted by a small number of have demonstrated discordant DNA methylation patterns adolescent or adult monozygotic (MZ) twin pairs. However, date, it remains unclear when such differences emerge, how prevalent they are across different tissues. To address this, we examined four differentially...
Comparison between groups of monozygotic (MZ) and dizygotic (DZ) twins enables an estimation the relative contribution genetic shared nonshared environmental factors to phenotypic variability. Using DNA methylation profiling ∼20,000 CpG sites as a phenotype, we have examined discordance levels in three neonatal tissues from 22 MZ 12 DZ twin pairs. exhibit wide range within-pair differences at birth, but show generally lower than Within-pair was lowest islands all increased function distance...
Abstract Background Biological aging estimators derived from DNA methylation data are heritable and correlate with morbidity mortality. Consequently, identification of genetic environmental contributors to the variation in these measures populations has become a major goal field. Results Leveraging SNP more than 40,000 individuals, we identify 137 genome-wide significant loci, which 113 novel, association study (GWAS) meta-analyses four epigenetic clocks surrogate markers for granulocyte...
Nicotinamide adenine dinucleotide (NAD+) precursor nicotinamide riboside (NR) has emerged as a promising compound to improve obesity-associated mitochondrial dysfunction and metabolic syndrome in mice. However, most short-term clinical trials conducted so far have not reported positive outcomes. Therefore, we aimed determine whether long-term NR supplementation boosts biogenesis health humans. Twenty body mass index (BMI)-discordant monozygotic twin pairs were supplemented with an escalating...
Abstract Background The extent to which development- and age-associated epigenetic changes are influenced by genetic, environmental stochastic factors remains be discovered. Twins provide an ideal model with investigate these influences but previous cross-sectional twin studies contradictory evidence of within-pair drift over time. Longitudinal can potentially address this discrepancy. Results In a pilot, genome-scale study DNA from buccal epithelium, relatively homogeneous tissue, we show...
Low mitochondrial number and activity have been suggested as underlying factors in obesity, type 2 diabetes, metabolic syndrome. However, the stage at which dysfunction manifests adipose tissue after onset of obesity remains unknown. Here we examined subcutaneous (SAT) samples from healthy monozygotic twin pairs, 22.8–36.2 years age, who were discordant (ΔBMI >3 kg/m2, mean length discordance 6.3 ± 0.3 years, n = 26) concordant <3 14) for body weight, assessed their detailed...
Tobacco smoking is a risk factor for multiple diseases, including cardiovascular disease and diabetes. Many smoking-associated signals have been detected in the blood methylome, but extent to which these changes are widespread metabolically relevant tissues, impact gene expression or metabolic health, remains unclear. We investigated DNA methylation variation adipose tissue biopsies from 542 healthy female twins. Replication, specificity, longitudinal stability of effects were explored...
Aim: Smoking strongly influences DNA methylation, with current and never smokers exhibiting different methylation profiles. Methods: To advance the practical applicability of smoking-associated signals, we used machine learning methodology to train a classifier for smoking status prediction. Results: We show prediction performance our on three independent whole-blood datasets demonstrating its robustness global applicability. Furthermore, examine reasons biologically meaningful...
Individuals with fast nicotine metabolism typically smoke more and thus have a greater risk for smoking-induced diseases. Further, the efficacy of smoking cessation pharmacotherapy is dependent on rate metabolism. Our objective was to use metabolite ratio (NMR), an established biomarker rate, in genome-wide association study (GWAS) identify novel genetic variants influencing A heritability estimate 0.81 (95% CI 0.70–0.88) obtained NMR using monozygotic dizygotic twins FinnTwin cohort. We...
Abstract The older Finnish Twin Cohort (FTC) was established in 1974. baseline survey 1975, with two follow-up health surveys 1981 and 1990. fourth wave of assessments done three parts, a questionnaire study twins born during 1945–1957 2011–2012, while were interviewed screened for dementia time periods, between 1999 2007 before 1938 2013 2017 1938–1944. content these 4 is described some initial results are described. In addition, we have invited twin-pairs, based on response to the...
Background: Adolescence is a stage of fast growth and development. Exposures during puberty can have long-term effects on health in later life. This study aims to investigate the role adolescent lifestyle biological aging. Methods: The participants originated from longitudinal FinnTwin12 (n = 5114). Adolescent lifestyle-related factors, including body mass index (BMI), leisure-time physical activity, smoking, alcohol use, were based self-reports measured at ages 12, 14, 17 years. For...
Abstract Background Metabolic syndrome (MetS) is associated with premature aging, but whether this association driven by genetic or lifestyle factors remains unclear. Methods Two independent discovery cohorts, consisting of twins and unrelated individuals, were examined ( N = 268, aged 23–69 years). The findings replicated in two cohorts from the same base population. One consisted individuals 1 564), other 293). Participants’ epigenetic age, estimated using blood DNA methylation data, was...
Abstract Background Machine learning (ML) classifiers are increasingly used for predicting cardiovascular disease (CVD) and related risk factors using omics data, although these outcomes often exhibit categorical nature class imbalances. However, little is known about which ML classifier, or upstream dimension reduction strategy has the strongest influence on prediction quality in such settings. Our study aimed to illustrate compare different machine strategies predict CVD under scenarios....
Familial clustering of endometrial carcinoma (EC) may occur as part hereditary nonpolyposis colorectal cancer (HNPCC), a multiorgan syndrome with mismatch repair (MMR) deficiency. Clustering EC alone, termed familial site-specific EC, constitute separate entity. Because its genetic basis is unknown, our purpose was to characterize such families molecularly.Twenty-three were identified among 519 consecutive patients diagnosed during 1986 1997. Tumor tissues examined for MMR protein expression...
The current epidemic of obesity and associated diseases calls for swift actions to better understand the mechanisms by which genetics environmental factors affect metabolic health in humans. Monozygotic (MZ) twin pairs showing discordance suggest that epigenetic influences represent one such mechanism. We studied genome-wide leukocyte DNA methylation variation 30 clinically healthy young adult MZ discordant body mass index (BMI; average within-pair BMI difference: 5.4 ± 2.0 kg/m2). There...
Previous reports link differential DNA methylation (DNAme) to environmental exposures that are associated with lung function. Direct evidence on function DNAme is, however, limited. We undertook an agnostic epigenome-wide association study (EWAS) pre-bronchodilation and its change in adults. In a discovery–replication EWAS design, blood spirometry were measured twice, 6–15 years apart, the same participants of three adult population-based discovery cohorts (n=2043). Associated markers...
ABSTRACT Purpose Greater leisure-time physical activity (LTPA) associates with healthier lives, but knowledge regarding occupational (OPA) is more inconsistent. DNA methylation (DNAm) patterns capture age-related changes in different tissues. We aimed to assess how LTPA and OPA are associated three DNAm-based epigenetic age estimates, namely, DNAm age, PhenoAge, GrimAge. Methods The participants were young adult (21–25 yr, n = 285) older (55–74 235) twin pairs, including 16 pairs documented...
Monozygotic (MZ) twins and higher-order multiples arise when a zygote splits during pre-implantation stages of development. The mechanisms underpinning this event have remained mystery. Because MZ twinning rarely runs in families, the leading hypothesis is that it occurs at random. Here, we show strongly associated with stable DNA methylation signature adult somatic tissues. This spans regions near telomeres centromeres, Polycomb-repressed heterochromatin, genes involved cell-adhesion, WNT...