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Background: Anthropometric measures show high heritability, and genetic correlations have been found between obesity-related traits. However, we lack a comprehensive analysis of the genetic background of human body morphology using detailed anthropometric measures., Methods: Height, weight, 7 skinfold thicknesses, 7 body circumferences and 4 body diameters (skeletal breaths) were measured in 214 pairs of twin children aged 3-18 years (87 monozygotic pairs) in the Autonomous Region of Madeira, Portugal. Factor analysis (Varimax rotation) was used to analyze the underlying structure of body physique. Genetic twin modeling was used to estimate genetic and environmental contributions to the variation and co-variation of the anthropometric traits., Results: Together, two factors explained 80% of the variation of all 22 anthropometric traits in boys and 73% in girls. Obesity measures (body mass index, skinfold thickness measures, as well as waist and hip circumferences) and limb circumferences loaded most strongly on the first factor, whereas height and body diameters loaded especially on the second factor. These factors as well as all anthropometric measures showed high heritability (80% or more for most of the traits), whereas the rest of the variation was explained by environmental factors not shared by co-twins. Obesity measures showed high genetic correlations (0.75-0.98). Height showed the highest genetic correlations with body diameter measures (0.58-0.76). Correlations between environmental factors not shared by co-twins were weaker than the genetic correlations but still substantial. The correlation patterns were roughly similar in boys and girls., Conclusions: Our results show high genetic correlations underlying the human body physique, suggesting that there are sets of genes widely affecting anthropometric traits. Better knowledge of these genetic variants can help to understand the development of obesity and other features of the human physique., (© 2023. The Author(s).)

Living in the same household exposes family members to shared environments and may be reflected in estimates of shared environment in twin analyses. The age at the separation of cotwins in a twin pair marks the end of such shared exposure, and the age of separation is commonly self-reported in studies. The objective of the study was to summarize the age at separation from residential records and use it to validate with self-reported separation status and age at the third and fourth wave of data collection in the FinnTwin12 cohort. Age at separation was generated from the address information, linking it to the Finnish Population information system since birth. Descriptive statistics by sex and zygosity are presented. The mean age at separation from residential records was 20.36 years old. Women separated earlier than men and dizygotic pairs earlier than monozygotic pairs. We also calculated the sensitivity and specificity with the self-reported separation status at waves 3 and 4, and interrater reliability with the self-reported separation age at wave 4. Age at separation from residential records had a relatively poor agreement with the self-report. This work enables us to use a more precise and objective measure for the shared environment in future twin studies.

We tested the causality between education and smoking using the natural experiment of discordant twin pairs allowing to optimally control for background genetic and childhood social factors. Data from 18 cohorts including 10,527 monozygotic (MZ) and same-sex dizygotic (DZ) twin pairs discordant for education and smoking were analyzed by linear fixed effects regression models. Within twin pairs, education levels were lower among the currently smoking than among the never smoking co-twins and this education difference was larger within DZ than MZ pairs. Similarly, education levels were higher among former smoking than among currently smoking co-twins, and this difference was larger within DZ pairs. Our results support the hypothesis of a causal effect of education on both current smoking status and smoking cessation. However, the even greater intra-pair differences within DZ pairs, who share only 50% of their segregating genes, provide evidence that shared genetic factors also contribute to these associations.

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). We additionally tested whether similarity in one domain translated into greater similarity in another. Results suggest that a lower degree of similarity in co-twins' exposome profiles was associated with greater differences in their behavior and substance use. The strongest association was identified between excessive drinking behavior and the external exposome. Overall, our study demonstrates how social behavior and especially substance use are connected to the internal and external exposomes, while controlling for familial confounders. [ABSTRACT FROM AUTHOR]

Background: Separating with close siblings and leaving the parental home at an early age represents a major life event for an adolescent (reflected by age at separation in a twin pair) and may predispose them to poor mental health. This study aims to examine the association of age at separation and residential mobility on depressive symptoms in late adolescence and young adulthood and to explore possible underlying genetic effects. Methods: Residential mobility consisted of the number and total distance of moves before age 17. Based on 3071 twins from the FinnTwin12 cohort, we used linear regression to assess the association of age at separation and residential mobility with General Behavior Inventory (GBI) scores at age 17 and in young adulthood. A higher GBI score indicated more depressive symptoms occurred. Then, the mixed model for repeated measures (MMRM) was used to visualize the scores' trajectory and test the associations, controlling for "baseline" state. Twin analyses with a bivariate cross-lagged path model were performed between the difference in GBI scores, between cotwins, and separation status for the potential genetic influence. Results: Compared to twins separated before age 17, twins who separated later had significantly lower GBI scores at age 17 and in young adulthood. In MMRM, separation at a later age and a higher number of moves were associated with a higher GBI score in young adulthood. A small genetic effect was detected wherein GBI within-pair differences at age 17 were associated with separation status before age 22 (coefficient: 0.01). Conclusion: The study provides valid evidence about the influence of siblings and family on depressive symptoms in later adolescence and young adulthood while finding some evidence for a reverse direction effect. This suggests more caution in the interpretation of results. A strong association between residential mobility and depressive symptoms was affirmed, although further detailed research is needed. [ABSTRACT FROM AUTHOR]

Background: The association of sleep bruxism with mortality has not been studied. Objectives: Altogether 12 040 subjects from the nationwide Finnish twin cohort were included in the analyses. We examined whether self‐reported sleep bruxism is associated with increased risk of mortality, and if so, whether the effect is independent of known common risk factors. The time span of the follow‐up was 30 years. Methods: Cox proportional hazards regression models (Hazard Ratios and their 95% Confidence Intervals) adjusted by age, sex and covariates were used to assess the effect of baseline bruxism status in 1990 on future mortality in 1990–2020. Results: The risk of mortality among all participants (n = 12 040), independent of missing covariates and adjusted by age and sex, was 40% higher in weekly bruxers than in never bruxers (HR 1.40, 95% CI 1.16–1.68, p <.001). However, when adjusted by all studied covariates, (n = 11 427) the risk was no longer observed (HR 1.04, 95% CI 0.86–1.25, p =.717). Despite the overall lack of between bruxism and mortality after adjustment for covariates, we examined the cause‐specific risks for major cause‐of‐death groups. There were no substantial associations of weekly bruxism with major disease outcomes by the fully adjusted hazard ratios for them. Conclusion: Bruxism does not kill—in line with its definition of being rather a behaviour (with all its phenotypes) than a disease. [ABSTRACT FROM AUTHOR]

Background: Due to different assessment modes employed, a clear picture of the prevalence of sleep bruxism across time cannot be formed. Moreover, studies on the persistent or fluctuating nature of sleep bruxism have yielded divergent and even contradictory results. The aim of the present study was to evaluate in a nationwide twin cohort whether self‐reported sleep bruxism was correlated longitudinally, pairwise and cross‐twin over a 20‐year period. Objectives: Self‐reported bruxism was assessed in 1990 and 2011 by mailed questionnaires in the Finnish Twin Cohort study of same‐sex twins born 1945–1957. Methods: We assessed the phenotypic stability over time for all participating individuals (n = 4992). Among zygosity verified pairs (n = 516 MZ and n = 837 DZ), we estimated the cross‐sectional zygosity correlations and the zygosity‐specific cross‐twin cross‐time correlations. Results: Reported bruxism appeared rather persistent over time without significant difference regarding zygosity. The overall phenotypic longitudinal correlation was 0.540 and somewhat higher in men (0.596) than in women (0.507). Pairwise trait correlations in 1990 and 2011 were higher in MZ than in DZ pairs. The cross‐twin cross‐time correlations were higher in MZ twins than in DZ twins, but less than the cross‐sectional MZ and DZ pairwise correlations. Conclusions: The higher correlation of reported sleep bruxism in the cross‐twin cross‐time analyses in MZ than in DZ pairs implies a genetic background for bruxism persistence. Also, bruxism over time in individual twins appears to be fairly persistent and somewhat higher in men than women. [ABSTRACT FROM AUTHOR]

Objective: This study investigated 36‐year BMI trajectories in twins whose BMI in young adulthood was below, within, or above their genetically predicted BMI, with a focus on twin pairs with large intrapair BMI differences (within‐pair ΔBMI ≥ 3 kg/m2). Methods: Together, 3227 like‐sexed twin pairs (34% monozygotic) were examined at age ~30 years in 1975 and followed up in 1981, 1990, and 2011. An individual's observed BMI in 1975 was considered within (±2.0), below (<−2.0), or above (>+2.0) genetically predicted BMI, measured by a polygenic risk score of 996,919 single nucleotide polymorphisms. Results: In monozygotic and dizygotic twin pairs with large intrapair BMI differences, the co‐twin with a higher observed BMI in 1975 deviated above predicted BMI more frequently (~2/3) than the co‐twin with a lower BMI deviated below prediction (~1/3). Individuals below, within, and above prediction in 1975 reached, respectively, normal weight, overweight, and obesity by 2011, with a mean BMI increase of 4.5 (95% CI: 4.3–4.8). Conclusions: Categorizing BMI as below, within, or above polygenic risk score‐predicted BMI helps identifying individuals who have been resistant or susceptible to weight gain. This may provide new insights into determinants and consequences of obesity. [ABSTRACT FROM AUTHOR]

Obesity-induced adipose tissue dysfunction can cause low-grade inflammation and downstream obesity comorbidities. Although preadipocytes may contribute to this pro-inflammatory environment, the underlying mechanisms are unclear. We used human primary preadipocytes from body mass index (BMI) -discordant monozygotic (MZ) twin pairs to generate epigenetic (ATAC-sequence) and transcriptomic (RNA-sequence) data for testing whether increased BMI alters the subnuclear compartmentalization of open chromatin in the twins' preadipocytes, causing downstream inflammation. Here we show that the co-accessibility of open chromatin, i.e. compartmentalization of chromatin activity, is altered in the higher vs lower BMI MZ siblings for a large subset (~ 88.5 Mb) of the active subnuclear compartments. Using the UK Biobank we show that variants within these regions contribute to systemic inflammation through interactions with BMI on C-reactive protein. In summary, open chromatin co-accessibility in human preadipocytes is disrupted among the higher BMI siblings, suggesting a mechanism how obesity may lead to inflammation via gene-environment interactions. Preadipocytes contribute to the pro-inflammatory environment in obesity, via unknown mechanisms. Here, comparing monozygotic twin pairs, the authors show that co-accessibility of chromatin in preadipocytes is altered in siblings with higher compared to lower BMI, and that variants in these regions contribute to systemic inflammation via interactions with BMI. [ABSTRACT FROM AUTHOR]

Introduction: Assortative mating refers describes a phenomenon in which individuals with similar phenotypic traits are more likely to mate and reproduce with each other; i.e. assortative mating occurs when individuals choose partners based on their similarity or dissimilarity in certain traits. to patterns of non-randommating of spouses leading to phenotypic resemblance. There are various theories about the its underlying mechanisms, which have different genetic consequences. Methods: Weanalyzed examined two possible mechanisms underlying assortative mating - phenotypic assortment and social homogamy - for educational attainment in two countries utilizing data of mono- and dizygotic twins and their spouses (1,451 Finnish and 1,616 Dutch twin-spouse pairs). Results: The spousal correlations were 0.51 in Finland and 0.45 in the Netherlands, to which phenotypic assortment contributed 0.35 and 0.30, and social homogamy 0.16 and 0.15, respectively. Conclusion: Both social homogamy and phenotypic assortment are important processes in spouse selection in Finland and the Netherlands. In both countries, phenotypic assortment contributes to a greater degree to the similarity of spouses than social homogamy. [ABSTRACT FROM AUTHOR]

Background: Obesity is a heritable complex phenotype that can increase the risk of age‐related outcomes. Biological age can be estimated from DNA methylation (DNAm) using various "epigenetic clocks." Previous work suggests individuals with elevated weight also display accelerated aging, but results vary by epigenetic clock and population. Here, we utilize the new epigenetic clock GrimAge, which closely correlates with mortality. Objectives: We aimed to assess the cross‐sectional association of body mass index (BMI) with age acceleration in twins to limit confounding by genetics and shared environment. Methods and results: Participants were from the Finnish Twin Cohort (FTC; n = 1424), including monozygotic (MZ) and dizygotic (DZ) twin pairs, and DNAm was measured using the Illumina 450K array. Multivariate linear mixed effects models including MZ and DZ twins showed an accelerated epigenetic age of 1.02 months (p‐value = 6.1 × 10–12) per one‐unit BMI increase. Additionally, heavier twins in a BMI‐discordant MZ twin pair (ΔBMI >3 kg/m2) had an epigenetic age 5.2 months older than their lighter cotwin (p‐value = 0.0074). We also found a positive association between log (homeostatic model assessment of insulin resistance) and age acceleration, confirmed by a meta‐analysis of the FTC and two other Finnish cohorts (overall effect = 0.45 years, p‐value = 4.1 × 10–25) from adjusted models. Conclusion: We identified significant associations of BMI and insulin resistance with age acceleration based on GrimAge, which were not due to genetic effects on BMI and aging. Overall, these results support a role of BMI in aging, potentially in part due to the effects of insulin resistance. [ABSTRACT FROM AUTHOR]

Background: We sought to clarify the impact of adolescent alcohol misuse on adult physical health and subjective well‐being. To do so, we investigated both the direct associations between adolescent alcohol misuse and early midlife physical health and life satisfaction and the indirect effects on these outcomes attributable to subsequent alcohol problems. Method: The sample included 2733 twin pairs (32% monozygotic; 52% female) from the FinnTwin16 study. Adolescent alcohol misuse was a composite of frequency of drunkenness, frequency of alcohol use, and alcohol problems at ages 16, 17, and 18.5. The early midlife outcomes included somatic symptoms, self‐rated health, and life satisfaction at age 34. The mediators examined as part of the indirect effect analyses included alcohol problems from the Rutgers Alcohol Problem Index at ages 24 and 34. Serial mediation and co‐twin comparison models were applied and included covariates from adolescence and early midlife. Results: There were weak direct associations between adolescent alcohol misuse and early midlife physical health and life satisfaction. However, there was stronger evidence for indirect effects, whereby young adult and early midlife alcohol problems serially mediated the relationship between adolescent alcohol misuse and early midlife somatic symptoms (β = 0.03, 95% CI [0.03, 0.04]), self‐rated health (β = −0.02, 95% CI [−0.03, −0.01]), and life satisfaction (β = −0.03, CI [−0.04, −0.02]). These serial mediation effects were robust in co‐twin comparison analyses. Conclusions: These results provide evidence that alcohol problems are a primary driver linking adolescent alcohol misuse and poor health outcomes across the lifespan. [ABSTRACT FROM AUTHOR]

Background: The sex gap in life expectancy has been narrowing in Finland over the past 4-5 decades; however, on average, women still live longer than men. Epigenetic clocks are markers for biological aging which predict life span. In this study, we examined the mediating role of lifestyle factors on the association between sex and biological aging in younger and older adults.Methods: Our sample consists of younger and older twins (21‒42 years, n = 1 477; 50‒76 years, n = 763) including 151 complete younger opposite-sex twin pairs (21‒30 years). Blood-based DNA methylation was used to compute epigenetic age acceleration by 4 epigenetic clocks as a measure of biological aging. Path modeling was used to study whether the association between sex and biological aging is mediated through lifestyle-related factors, that is, education, body mass index, smoking, alcohol use, and physical activity.Results: In comparison to women, men were biologically older and, in general, they had unhealthier life habits. The effect of sex on biological aging was partly mediated by body mass index and, in older twins, by smoking. Sex was directly associated with biological aging and the association was stronger in older twins.Conclusions: Previously reported sex differences in life span are also evident in biological aging. Declining smoking prevalence among men is a plausible explanation for the narrowing of the difference in life expectancy between the sexes. Data generated by the epigenetic clocks may help in estimating the effects of lifestyle and environmental factors on aging and in predicting aging in future generations. [ABSTRACT FROM AUTHOR]

Background: Do drinking patterns in late adolescence/early adulthood predict lifetime childlessness and number of children? Research on this question has been only tangentially relevant and the results inconsistent. The designs used to date have been compromised by genetic and environmental confounds that are poorly controlled; covariate effects of smoking and education that are often ignored; males being understudied; population‐based sampling rare, and long‐term prospective studies with genetically informative designs yet to be reported. Method: In a 33‐year follow‐up, we linked the drinking patterns of >3500 Finnish twin pairs, assessed at ages 18–25, to registry data on their eventual number of children. Analyses distinguished associations of early drinking patterns with lifetime childlessness from those predictive of family size. Within‐twin pair analyses used fixed‐effects regression models to account for shared familial confounds and genetic liabilities. Childlessness was analyzed with Cox proportional hazards models and family size with Poisson regression. Analyses within‐pairs and of twins as individuals were run before and after adjustment for smoking and education, and for oral contraceptive (OC) use in individual‐level analyses of female twins. Results: Baseline abstinence and heavier drinking both significantly predicted lifetime childlessness in individual‐level analyses. Few abstinent women used OCs, but they were nonetheless more often eventually childless; adjusting for smoking and education did not affect this finding. Excluding childless twins, Poisson models of family size showed heavier drinking at 18–25 to be predictive of fewer children in both men and women. Those associations were replicated in within‐pair analyses of dizygotic twins, each level of heavier drinking being associated with smaller families. Among monozygotic twins, associations of drinking with completed family size yielded effects of similar magnitude, reaching significance at the highest levels of consumption, ruling out familial confounds. Conclusions: Compared to moderate levels of drinking, both abstinence and heavier drinking in late adolescence/early adulthood predicted a greater likelihood of lifetime childlessness and eventual number of children. Familial confounds do not fully explain these associations. [ABSTRACT FROM AUTHOR]

The discordant twin pair study design is powerful to control for familial confounding. We employed this approach to investigate the associations of smoking with several cancers. The NorTwinCan study combines data from the Danish, Finnish, Norwegian and Swedish twin and cancer registries. Follow‐up started when smoking status was determined and ended at cancer diagnosis confirmed by information in the cancer registry, death or end of follow‐up. We classified the participants as never (n = 59 093), former (n = 21 168) or current (n = 47 314) smokers. We pooled data from twin pairs where one co‐twin was diagnosed with any of the following tobacco‐related cancers: esophagus, kidney, larynx, liver, oral cavity, pancreas, pharynx or urinary bladder, while their co‐twin had none of those. Lung cancer was included in further analysis. We used Cox regression allowing for pair‐specific baseline functions to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). For tobacco‐related cancer sites, we recorded 7379 cases during median 27 years of follow‐up. The analyses based on individual twins showed that former (HR 1.31, 95% CI: 1.17‐1.48) and current (HR 2.14 [1.95‐2.34]) smokers are at increased risk to develop one of cancers listed above, compared to never smokers. Among 109 monozygotic twin pairs discordant for cancer and smoking, the HR was 1.85 (95% CI: 1.15‐2.98) among current smokers and 1.69 (1.00‐2.87) among former smokers when compared to their never smoking co‐twin. Thus, associations of smoking with several cancers were replicated for discordant identical twin pairs. Analyses based on genetically informative data provide evidence consistent with smoking causing multiple cancers. [ABSTRACT FROM AUTHOR]

The article discusses research which found that smoking cessation is not associated with a decline in reported sleep bruxism in middle-aged Finnish twins. The study considered the role of environmental factors in the aetiology of sleep bruxism. It used Chi-square test to analyze the bruxism status of Finnish twins in 2011 and whether smoking cessation during 1990-2011 was associated with it.

Background higher educational attainment and less midlife cardiovascular risk factors are related to better old-age cognition. Whether education moderates the association between cardiovascular risk factors and late-life cognition is not known. We studied if higher education provides resilience against the deteriorative effects of higher middle-age body mass index (BMI) and a combination of midlife cardiovascular risk factors on old-age cognition. Methods the study population is the older Finnish Twin Cohort (n  = 4,051, mean age [standard deviation, SD] = 45.5 years [6.5]). Cardiovascular risk factors and education were studied at baseline with questionnaires in 1975, 1981 and/or 1990 (participation rates of 89, 84 and 77%, respectively). Cognition was evaluated with telephone interviews (participation rate 67%, mean age [SD] =73.4 [2.9] years, mean follow-up [SD] = 27.8 [6.0] years) in 1999–2017. We studied the main and interactive effects of education and BMI/dementia risk score on late-life cognition with linear regression analysis. The study design was formulated before the pre-defined analyses. Results years of education moderated the association between BMI with old-age cognition (among less educated persons, BMI-cognition association was stronger [ B  = −0.24 points per BMI unit, 95% CI −0.31, −0.18] than among more educated persons [ B  = −0.06 points per BMI unit, 95% CI −0.16, 0.03], P interaction < 0.01). There was a similar moderating effect of education on dementia risk score consisting of cardiovascular risk factors (P  < 0.001). Conclusions our results support the cognitive reserve hypothesis. Those with higher education may tolerate the deteriorative effects of midlife cardiovascular risk factors on old-age cognition better than those with lower education. [ABSTRACT FROM AUTHOR]

- We studied cortical amyloid – episodic memory association in twin pairs - Cognitively discordant twin pairs were identified using telephone interview - 45 twin pairs participated in PET imaging and in-person neuropsychological testing - Within-twin pair differences in amyloid and memory were associated with each other - Higher amyloid is related to poorer memory even when controlling for genetic effects We studied the association between episodic memory and cortical fibrillar β-amyloid pathology within twin pairs. Using telephone-administered cognitive screening of 1415 twin pairs in a population-based older Finnish Twin Cohort study, we identified 45 (mean [SD] age 72.9 [4.0] years, 40% women) cognitively discordant same-sex twin pairs (24 dizygotic and 21 monozygotic) without neurological or psychiatric disorders other than AD or mild cognitive impairment. In-person neuropsychological testing was conducted. Cortical amyloid was measured with carbon 11-labelled Pittsburgh compound B ([11C]PiB) positron emission tomography imaging and quantified as the average standardized uptake value ratio in cortical regions affected in AD. Larger within-twin pair differences in verbal immediate (r = -0.42) and delayed free recall (r = -0.41), and visual delayed free recall (r = -0.46) were associated with larger within-twin pair differences in [11C]PiB uptake (p 's < 0.01). Correlations were not significantly different in dizygotic and monozygotic pairs suggesting that the episodic memory-cortical amyloid relationship is not confounded by genetic effects. However, larger samples are needed to draw more definitive conclusions. [ABSTRACT FROM AUTHOR]

Background: Adipose stromal/stem cells (ASCs) are promising candidates for future clinical applications. ASCs have regenerative capacity, low immunogenicity, and immunomodulatory ability. The success of future cell-based therapies depends on the appropriate selection of donors. Several factors, including age, sex, and body mass index (BMI), may influence ASC characteristics. Our aim was to investigate the effect of acquired weight on ASC characteristics under the same genetic background using ASCs derived from monozygotic (MZ) twin pairs. Methods: ASCs were isolated from subcutaneous adipose tissue from five weight-discordant (WD, within-pair difference in BMI > 3 kg/m2) MZ twin pairs, with measured BMI and metabolic status. The ASC immunophenotype, proliferation and osteogenic and adipogenic differentiation capacity were studied. ASC immunogenicity, immunosuppression capacity and the expression of inflammation markers were investigated. ASC angiogenic potential was assessed in cocultures with endothelial cells. Results: ASCs showed low immunogenicity, proliferation, and osteogenic differentiation capacity independent of weight among all donors. ASCs showed a mesenchymal stem cell-like immunophenotype; however, the expression of CD146 was significantly higher in leaner WD twins than in heavier cotwins. ASCs from heavier twins from WD pairs showed significantly greater adipogenic differentiation capacity and higher expression of TNF and lower angiogenic potential compared with their leaner cotwins. ASCs showed immunosuppressive capacity in direct cocultures; however, heavier WD twins showed stronger immunosuppressive capacity than leaner cotwins. Conclusions: Our genetically matched data suggest that a higher weight of the donor may have some effect on ASC characteristics, especially on angiogenic and adipogenic potential, which should be considered when ASCs are used clinically. [ABSTRACT FROM AUTHOR]

Simple Summary: Smoking is associated with a moderate increased risk of Hodgkin and follicular lymphoma. To help understand why, we examined lymphoma-related biomarker levels among 134 smoking and non-smoking twins (67 pairs) ascertained from the Finnish Twin Cohort. We validated self-reported smoking history by measuring serum cotinine, a metabolite of nicotine, from previously collected frozen serum samples. In total, 27 immune biomarkers were assayed using the Luminex Multiplex platform (R & D Systems). We found that four immune response biomarkers were higher and one was lower among smoking compared to non-smoking twins. The strongest association was observed for CCL17/TARC, a biomarker elevated in Hodgkin lymphoma patients. Immune biomarker levels were similar in former smokers and non-smokers. Current smoking may increase levels of immune proteins that could partially explain the association between smoking and risk of certain lymphomas. Smoking is associated with a moderate increased risk of Hodgkin and follicular lymphoma. To understand why, we examined lymphoma-related biomarker levels among 134 smoking and non-smoking twins (67 pairs) ascertained from the Finnish Twin Cohort. Previously collected frozen serum samples were tested for cotinine to validate self-reported smoking history. In total, 27 immune biomarkers were assayed using the Luminex Multiplex platform (R & D Systems). Current and non-current smokers were defined by a serum cotinine concentration of >3.08 ng/mL and ≤3.08 ng/mL, respectively. Associations between biomarkers and smoking were assessed using linear mixed models to estimate beta coefficients and standard errors, adjusting for age, sex and twin pair as a random effect. There were 55 never smokers, 43 current smokers and 36 former smokers. CCL17/TARC, sgp130, haptoglobin, B-cell activating factor (BAFF) and monocyte chemoattractant protein-1 (MCP1) were significantly (p < 0.05) associated with current smoking and correlated with increasing cotinine concentrations (Ptrend < 0.05). The strongest association was observed for CCL17/TARC (Ptrend = 0.0001). Immune biomarker levels were similar in former and never smokers. Current smoking is associated with increased levels of lymphoma-associated biomarkers, suggesting a possible mechanism for the link between smoking and risk of these two B-cell lymphomas. [ABSTRACT FROM AUTHOR]

• Obesity matrisome include 130 signature genes in adipose tissue and 71 in adipocytes. • Adipocyte obesity matrisome show hypertrophic inflammatory phenotype. • Adipose tissue obesity matrisome shows remodeling phenotype. • Novel metabolism-linked matrisome genes are CTSA, CSTO, FAM20B and NGLY1. Adipose tissue is a central regulator of metabolic health and its failure in obesity is a major cause of weight associated comorbidities, such as type 2 diabetes. Many extracellular matrix proteins, represented by matrisome, play a critical role in balancing adipose tissue health and dysfunction. Extracellular matrix components, produced by different cell types of adipose tissue, can modulate adipocyte function, tissue remodeling during expansion, angiogenesis, and inflammation and also form fibrotic lesions in the tissue. In this study, we investigated changes in matrisome of whole adipose tissue and adipocytes in human obesity. We investigated further the networks and biological pathways of the genes related to the changes and their association to development of metabolic dysfunction linked to type 2 diabetes. We used transcriptome data and clinical metabolic parameters from a rare weight-discordant MZ twin cohort. The Heavy-Lean differential matrisome gene expression (Δmatrisome) and differential metabolic parameters reflect changes in adipose tissue upon weight gain and changes in whole body glucose, insulin metabolism, as well as lipid status. We report that obesity Δmatrisome shows high specificity with 130 and 71 of the 1068 matrisome genes showing altered expression in the adipose tissue and adipocytes of heavier co-twin, respectively. The Δmatrisome differs considerably between adipose tissue vs adipocytes which reflects inflammation of hypertrophic adipocytes and the remodeling activity of the rest of the tissue resident cells. The obesity Δmatrisome is discussed extensively in the light of existing evidence and novel significant associations to obesity are reported to matrisome genes; cathepsin A, cathepsin O, FAM20B and N-glycanase1. [ABSTRACT FROM AUTHOR]

Abnormal blood pressure is strongly associated with risk of high-prevalence diseases, making the study of blood pressure a major public health challenge. Although biological mechanisms underlying hypertension at the single omic level have been discovered, multi-omics integrative analyses using continuous variations in blood pressure values remain limited. We used a multi-omics regression-based method, called sparse multi-block partial least square, for integrative, explanatory, and predictive interests in study of systolic and diastolic blood pressure values. Various datasets were obtained from the Finnish Twin Cohort for up to 444 twins. Blocks of omics—including transcriptomic, methylation, metabolomic—data as well as polygenic risk scores and clinical data were integrated into the modeling and supported by cross-validation. The predictive contribution of each omics block when predicting blood pressure values was investigated using external participants from the Young Finns Study. In addition to revealing interesting inter-omics associations, we found that each block of omics heterogeneously improved the predictions of blood pressure values once the multi-omics data were integrated. The modeling revealed a plurality of clinical, transcriptomic, and metabolomic factors consistent with the literature and that play a leading role in explaining unit variations in blood pressure. These findings demonstrate (1) the robustness of our integrative method to harness results obtained by single omics discriminant analyses, and (2) the added value of predictive and exploratory gains of a multi-omics approach in studies of complex phenotypes such as blood pressure. [ABSTRACT FROM AUTHOR]

Introduction: Participation in diverse physical activities has beneficial health effects. However, little is known on how genetic and environmental factors affect this trait. Thus, we examined to what extent these factors explain participation in diverse leisure-time physical activities from late adolescence to adulthood using a twin study design. Methods : The participants were Finnish twins who reported their participation in diverse leisure-time physical activities at ages 17 (n = 5429) and 34 yr (n = 4246). The number of physical activities engaged in was analyzed using applications of structural linear modeling for twin data. Results : On average, the total number of physical activities engaged in during leisure time was slightly over three at both ages and in both sexes, with moderate heritability estimates (40%-58%) from adolescence to adulthood. Environmental factors shared by co-twins (e.g. childhood family environment) influenced only in adolescence, being higher for women. Environmental influences unique to each co-twin explained the remaining variances (34%-57%), being higher at age 34 yr. Participation in diverse leisure-time physical activities correlated moderately between ages 17 and 34 yr (men: r trait = 0.30, 95% confidence interval [CI] = 0.25-0.35; women: r trait = 0.26, 95% CI = 0.22-0.31). In addition, genetic influences on participation in physical activities correlated moderately between adolescence and adulthood (r A = 0.51, 95% CI = 0.39-0.64, and 0.44, 95% CI = 0.34-0.55, respectively). These common genetic influences explained 93% of the trait correlations found in men and 85% in women. Conclusions : Genetic and unique environmental influences explain a large proportion of variation in the number of leisure-time physical activities. However, the estimates vary by age and sex. Common genetic background mainly explains the continuity of the participation in diverse leisure-time physical activities between adolescence and adulthood. [ABSTRACT FROM AUTHOR]