Protein Associations With Alcohol Consumption and Genetic Risk for Alcohol-Related Sociomedical Conditions.

Studies investigating proteomic associations with alcohol consumption and the genetic links of these proteins to alcohol-related traits are scarce. The aims of our study were (1) to identify proteins associated with alcohol consumption and (2) to investigate the molecular pathways and genetics linking the identified proteins to alcohol consumption and related sociomedical conditions. We generated proteomic and genotypic data from blood samples of 387 Finnish twins (age range: 56-70) and calculated polygenic risk scores (PRSs) of eight alcohol-related traits: obesity, alcohol dependence, number of drinks per week, number of cigarettes per day, major depressive disorders (MDDs), schizophrenia, externalising behaviour and educational attainment.

Biological aging acceleration in major depressive disorder: a multi-omics, multi-modal analyses.

Major depressive disorder (MDD) is linked to a higher risk of premature aging, but the mechanisms underlying this association remain unclear. Using data from two population cohorts (UK Biobank and Finnish Twin Cohort), we evaluate the relationship between systemic and organ-specific proteomic and epigenetic aging acceleration and MDD. A lifetime history of MDD was associated with accelerated proteomic aging at both systemic and organ-specific levels-including the brain-in both cohorts, with stronger associations than those observed with systemic epigenetic aging.

Genetic and environmental effects on weight gain from young adulthood to old age and its association with body mass index at early young adulthood: an individual-based pooled analysis of 16 twin cohorts.

Introduction: Genetic factors contribute to weight gain, but how these effects change over adulthood is still unknown. We studied the impact of genetics on BMI change from young adulthood to old age and its relationship with BMI in early young adulthood.

Data And Methods: Data from 16 longitudinal twin cohorts, including 111,370 adults (56% women) and 55,657 complete twin pairs (42% monozygotic), were pooled.

A proteomic signature of healthspan.

The focus of aging research has shifted from increasing lifespan to enhancing healthspan to reduce the time spent living with disability. Despite significant efforts to develop biomarkers of aging, few studies have focused on biomarkers of healthspan. We developed a proteomics-based signature of healthspan [healthspan proteomic score (HPS)] using proteomic data from the Olink Explore 3072 assay in the UK Biobank Pharma Proteomics Project (53,018 individuals and 2,920 proteins).

Molecular landscape of sex- and modality-specific exercise adaptation in human skeletal muscle through large-scale multi-omics integration.

We investigated the molecular mechanisms of exercise adaptations in human muscle by integrating genome, methylome, transcriptome, and proteome data from over 1,000 participants (2,340 muscle samples). We identified distinctive signatures associated with maximal oxygen consumption (VO), and multi-omics integration uncovered five key genes as robust exercise markers across layers, with transcription factors functioning as activators, synergizing with DNA methylation to regulate gene expression. Minimal sex differences were observed, while modality-specific analysis highlighted distinct pathways for aerobic and resistance exercise, contrasting with muscle disuse patterns.

Twin Study Provides Heritability Estimates for 2321 Plasma Proteins and Assesses Missing SNP Heritability.

Assessing how much variability in blood plasma proteins is due to genetic or environmental factors is essential for advancing personalized medicine. While large-scale studies have established SNP-based heritability (SNP-h) estimates for plasma proteins, less is known about the proportion of total genetic effects on protein variability. We applied quantitative genetic twin models to estimate the heritability of 2321 plasma proteins and to assess the proportion of heritability accounted for by SNP-h estimates.

Twin pair analysis uncovers links between DNA methylation, mitochondrial DNA quantity and obesity.

Alterations in mitochondrial metabolism in obesity may indicate disrupted communication between mitochondria and nucleus, and DNA methylation may influence this interplay. Here, we leverage data from the Finnish Twin Cohort study subcohort (n = 173; 86 full twin pairs, 1 singleton), including comprehensive measurements of obesity-related outcomes, mitochondrial DNA quantity and nuclear DNA methylation levels in adipose and muscle tissue, to identify one CpG at SH3BP4 significantly associated with mitochondrial DNA quantity in adipose tissue (FDR < 0.05).

Proteomic associations with fluctuation and long-term changes in BMI: A 40-year follow-up study.

Introduction: While some studies have explored associations between weight change and blood proteins, most have been intervention-based, offering limited insight into proteomic associations with long-term weight gain. It remains unclear whether plasma proteins are related to BMI fluctuation over time. This study investigates associations of long-term BMI changes and fluctuations with over 1000 plasma proteins involved in cardiometabolic and inflammation functions.

Multi-Omic Associations of Epigenetic Age Acceleration Are Heterogeneously Shaped by Genetic and Environmental Influences.

Connections between the multi-ome and epigenetic age acceleration (EAA), and especially whether these are influenced by genetic or environmental factors, remain underexplored. We therefore quantified associations between the multi-ome comprising four layers-the proteome, metabolome, external exposome (here, sociodemographic factors), and specific exposome (here, lifestyle)-with six different EAA estimates. Two twin cohorts were used in a discovery-replication scheme, comprising, respectively, young (N = 642; mean age = 22.

Proteomic associations with fluctuation and long-term changes in BMI: A 40-year follow-up study.

Introduction: While some studies have explored associations between weight change and blood proteins, most have been intervention-based, offering limited insight into proteomic associations with long-term weight gain. It remains unclear whether plasma proteins are related to BMI fluctuation over time. This study investigates associations of long-term BMI changes and fluctuations with over 1,000 plasma proteins involved in cardiometabolic and inflammation functions.

The associations of long-term physical activity in adulthood with later biological ageing and all-cause mortality - a prospective twin study.

Objectives: The association between leisure-time physical activity (LTPA) and a lower risk of mortality is susceptible to bias from multiple sources. We investigated the potential of biological ageing to mediate the association between long-term LTPA and mortality and whether the methods used to account for reverse causality affect the interpretation of this association.

Methods: Study participants were twins from the older Finnish Twin Cohort (n = 22,750; 18-50 years at baseline).

Glycemic control in women with GDM: insights from a randomized controlled pilot trial on plant-based Nordic healthy diet versus moderately carbohydrate restricted diet.

Background: Gestational Diabetes Mellitus (GDM) prevalence is rising worldwide, but optimal dietary strategies remain unclear. The eMOM pilot RCT compared a plant-protein rich Healthy Nordic Diet (HND) and a moderately carbohydrate restricted diet (MCRD) and their potential effects on time in glucose target range (≤ 7.8 mmol/L, %TIR), and on newborn body composition.

Suboptimal dietary patterns are associated with accelerated biological aging in young adulthood: A study with twins.

Background & Aims: Suboptimal diets increase morbidity and mortality risk. Epigenetic clocks are algorithms that can assess health and lifespan, even at a young age, before clinical manifestations of diseases. We investigated the association between dietary patterns and biological aging in young adult twins.

Transcriptomic and Metabolomic Analyses in Monozygotic and Dizygotic Twins.

Monozygotic (MZ) and dizygotic (DZ) twins are studied to understand genetic and environmental influences on complex traits, however the mechanisms behind twinning are not completely understood. (Epi)genomic studies identified SNPs associated with DZ twinning and DNA methylation sites with MZ twinning. To find molecular biomarkers of twinning, we compared transcriptomics and metabolomics data from MZ and DZ twins.

Pre-diagnosis blood DNA methylation profiling of twin pairs discordant for breast cancer points to the importance of environmental risk factors.

Background: Assessment of breast cancer (BC) risk generally relies on mammography, family history, reproductive history, and genotyping of major mutations. However, assessing the impact of environmental factors, such as lifestyle, health-related behavior, or external exposures, is still challenging. DNA methylation (DNAm), capturing both genetic and environmental effects, presents a promising opportunity.

Lifestyle differences between co-twins are associated with decreased similarity in their internal and external exposome profiles.

Whether differences in lifestyle between co-twins are reflected in differences in their internal or external exposome profiles remains largely underexplored. We therefore investigated whether within-pair differences in lifestyle were associated with within-pair differences in exposome profiles across four domains: the external exposome, proteome, metabolome and epigenetic age acceleration (EAA). For each domain, we assessed the similarity of co-twin profiles using Gaussian similarities in up to 257 young adult same-sex twin pairs (54% monozygotic).

A Bivariate Twin Study of Lifetime cannabis Initiation and Lifetime Regular Tobacco Smoking Across Three Different Countries.

Regular cigarette smoking and cannabis consumption are strongly positively related to each other, yet few studies explore their underlying variation and covariation. We evaluated the genetic and environmental decomposition of variance and covariance of these two traits in twin data from three countries with different social norms and legislation. Data from the Netherlands Twin Register, FinnTwin12/16, and the Minnesota Center for Twin Family Research (total N = 21,617) were analyzed in bivariate threshold models of lifetime regular smoking initiation (RSI) and lifetime cannabis initiation (CI).

A proteomic signature of healthspan.

The focus of aging research has shifted from increasing lifespan to enhancing healthspan to reduce the time spent living with disability. Despite significant efforts to develop biomarkers of aging, few studies have focused on biomarkers of healthspan. We developed a proteomics-based signature of healthspan (healthspan proteomic score (HPS)) using proteomic data from the Olink Explore 3072 assay in the UK Biobank Pharma Proteomics Project (53,018 individuals and 2920 proteins).

Exploring machine learning strategies for predicting cardiovascular disease risk factors from multi-omic data.

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 and class imbalances. However, little is known about which ML classifier, omics data, or upstream dimension reduction strategy has the strongest influence on prediction quality in such settings. Our study aimed to illustrate and compare different machine learning strategies to predict CVD risk factors under different scenarios.

Enhanced resolution profiling in twins reveals differential methylation signatures of type 2 diabetes with links to its complications.

Background: Type 2 diabetes (T2D) susceptibility is influenced by genetic and environmental factors. Previous findings suggest DNA methylation as a potential mechanism in T2D pathogenesis and progression.

Methods: We profiled DNA methylation in 248 blood samples from participants of European ancestry from 7 twin cohorts using a methylation sequencing platform targeting regulatory genomic regions encompassing 2,048,698 CpG sites.

Metabolic syndrome and epigenetic aging: a twin study.

Background: Metabolic syndrome (MetS) is associated with premature aging, but whether this association is 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 were replicated in two cohorts from the same base population.

Lifestyle differences between co-twins are associated with decreased similarity in their internal and external exposome profiles.

Whether differences in lifestyle between co-twins are reflected in differences in their internal or external exposome profiles remains largely underexplored. We therefore investigated whether within-pair differences in lifestyle were associated with within-pair differences in exposome profiles across four domains: the external exposome, proteome, metabolome and epigenetic age acceleration (EAA). For each domain, we assessed the similarity of co-twin profiles using Gaussian similarities in up to 257 young adult same-sex twin pairs (54% monozygotic).

TWINGEN - protocol for an observational clinical biobank recall and biomarker study to identify individuals with high risk of Alzheimer's disease.

Introduction: A better understanding of the earliest stages of Alzheimer's disease (AD) could expedite the development or administration of treatments. Large population biobanks hold the promise to identify individuals at an elevated risk of AD and related dementias based on health registry information. Here, we establish the protocol for an observational clinical recall and biomarker study called TWINGEN with the aim to identify individuals at high risk of AD by assessing cognition, health and AD-related biomarkers.

DNA methylation sites in early adulthood characterised by pubertal timing and development: a twin study.

Background: Puberty is a highly heritable and variable trait, with environmental factors having a role in its eventual timing and development. Early and late pubertal onset are both associated with various diseases developing later in life, and epigenetic characterisation of pubertal timing and development could lead to important insights. Blood DNA methylation, reacting to both genotype and environment, has been associated with puberty; however, such studies are relatively scarce.