Kaikki aineistot
Lisää
Aims To control for familial confounds, we studied the association between adolescent physical activity and later smoking in twin siblings discordant for their baseline physical activity. Design and measurements In this prospective population‐based twin study, we asked whether persistent physical activity/inactivity in adolescence (assessed at 16, 17 and 18.5 years) predicted questionnaire‐reported daily smoking at ages 22–27. Twins who, on the three baseline questionnaires, consistently reported frequent leisure physical activity (more than three times weekly) were classified as persistent exercisers, those who exercised less than three times monthly were called persistently inactive, others were occasional exercisers. Setting Finland. Participants A total of 4240 individuals, including 1870 twin pairs. Findings In analyses of individual twins, compared to persistent activity, persistent physical inactivity predicted increased risk of daily smoking (age‐ and sex‐adjusted odds ratio 5.53, 95% confidence interval 3.88–7.88, P < 0.001). The risk remained elevated even after excluding all those who had smoked 50 cigarettes or more life‐time at baseline and adjusted for educational level in adolescence. In within‐pair analyses compared to the active members of discordant twin pairs, the physically inactive co‐twins had increased risk of future daily smoking (sex‐adjusted odds ratio 3.39, 95% confidence interval 1.56–7.39, P = 0.002). Conclusions Persistent physical inactivity in adolescence relates to adult smoking, even after familial factors are taken into account.
Abstract Genetic and early environmental differences including early health habits associate with future health. To provide insight on the causal nature of these associations, monozygotic (MZ) twin pairs discordant for health habits provide an interesting natural experiment. Twin pairs discordant for leisure-time physical activity (LTPA) in early adult life is thus a powerful study design to investigate the associations between long-term LTPA and indicators of health and wellbeing. We have identified 17 LTPA discordant twin pairs from two Finnish twin cohorts and summarize key findings of these studies in this paper. The carefully characterized rare long-term LTPA discordant MZ twin pairs have participated in multi-dimensional clinical examinations. Key findings highlight that compared with less active twins in such MZ twin pairs, the twins with higher long-term LTPA have higher physical fitness, reduced body fat, reduced visceral fat, reduced liver fat, increased lumen diameters of conduit arteries to the lower limbs, increased bone mineral density in loaded bone areas, and an increased number of large high-density lipoprotein particles. The findings increase our understanding on the possible site-specific and system-level effects of long-term LTPA.
Studies of singletons suggest that right-handed individuals may have higher levels of testosterone than do left-handed individuals. Prenatal testosterone levels are hypothesised to be especially related to handedness formation. In humans, female members from opposite-sex twin pairs may experience elevated level of prenatal exposure to testosterone in their intrauterine environment shared with a male. We tested for differences in rates of left-handedness/right-handedness in female twins from same-sex and opposite-sex twin pairs. Our sample consisted of 4736 subjects, about 70% of all Finnish twins born in 1983–1987, with information on measured pregnancy and birth related factors. Circulating testosterone and estradiol levels at age 14 were available on 771 and 744 of these twins, respectively. We found significantly (p = .006) lower prevalence of left-handedness in females from opposite-sex pairs (5.3%) compared to females from same-sex pairs (8.6%). The circulating levels of neither testosterone nor estradiol related to handedness in either females or males. Nor were there differences in circulating testosterone or estradiol levels between females from opposite-sex and same-sex twin pairs. Birth and pregnancy related factors for which we had information were unrelated to handedness. Our results are difficult to fully explain by postnatal factors, but they offer support to theory that relates testosterone to formation of handedness, and in a population-based sample, are suggestive of effects of prenatal testosterone transfer.
Among adolescents, many parenting practices have been associated with the initiation and development of drinking behaviors. However, recent studies suggest discrepancies in parents' and adolescents' perceptions of parenting and their links with adolescent use. In this study, we derive two independent sets of underlying parenting profiles (based on parent and adolescent reported behaviors at age 11–12 years), which were then examined in relation to adolescents' drinking behaviors at ages 14 and 17½. Results indicated that the two sets of profiles accounted for little shared variance, with those based on adolescents' reports being stronger predictors of adolescent drinking. Moreover, comparisons of drinking levels across profiles pointed to multiple parenting strategies that may effectively reduce adolescent alcohol experimentation, including simply sustaining a moderate level of awareness of adolescents' whereabouts and activities and avoiding excessive conflict and strictness.
Introduction Genetic factors contribute to individual differences in physical activity, but it remains uncertain whether the magnitude of the genetic effects is modified by variations in home environments. We aimed to examine to what extent the psychosocial home environment in childhood and adolescence modifies the genetic influences on leisure time physical activity in young adulthood. Methods Participants were Finnish twins (N = 3305) who reported their leisure time physical activity at age 24 yr. The psychosocial home environment was assessed by twins at ages 12, 14, and 17 yr, as well as by their parents when the twins were age 12 yr. Gene–environment interaction modeling was performed with OpenMx software. Results Parental ratings of positive home atmosphere as well as the twins’ ratings of both positive home atmosphere at age 14 yr and lower relational tensions at ages 12 and 14 yr predicted higher leisure time physical activity levels in young adulthood (regression coefficients = 0.33–0.64). Parental perceptions as well as the twins’ perceptions of positive home atmosphere at ages 14 and 17 yr increased the additive genetic variation (moderation effects: 0.55, 95% confidence interval [CI] = 0.29–0.80; 0.60, 95% CI = 0.26–1.05; and 0.52, 95% CI = 0.19–0.87, respectively). The twins’ ratings of positive home atmosphere at age 12 yr and lower relational tensions at ages 12 and 14 yr increased the unique environmental variation of their subsequent physical activity (moderation effects: 0.46, 95% CI = 0.19–0.60; 0.48, 95% CI = 0.29–0.64; and 0.85, 95% CI = 0.12–0.95, respectively). Conclusions A psychosocial home environment that is warm and supportive in childhood and adolescence not only increases the mean level of subsequent leisure time physical activity in young adulthood but also modifies the genetic and environmental variances in leisure time physical activity.
Background Former participants in sports characterised by low intensity repetitive head impact appear to have elevated rates of later dementia, but links with other psychological health outcomes such as depression and suicide are uncertain. We quantified the occurrence of these endpoints in former contact sports athletes against general population controls using new data from a cohort study and a meta-analysis. Methods The cohort study comprised 2004 retired male athletes, who had competed internationally as amateurs for Finland across a range of sports, and 1385 general population controls. All study members were linked to mortality and hospitalisation registries. In the PROSPERO-registered systematic review (CRD42022352780), we searched PubMed and Embase to October 31 2022 for cohort studies that reported standard estimates of association and precision. Study-specific estimates were aggregated in a random-effect meta-analysis. The Newcastle-Ottawa Scale was used to appraise the quality of each study. Findings In survival analyses of the Finnish cohort data, former boxers (depression: hazard ratio 1.43 [95% CI 0.73, 2.78]; suicide: 1.75 [0.64, 4.38]), Olympic-style wrestlers (depression: 0.94 [0.44, 2.00]; suicide: 1.60 [0.64, 3.99]), and soccer players (depression: 0.62 [0.26, 1.48]; suicide: 0.50 [0.11, 2.16]) did not have statistically higher rates of major depressive disorder or suicide at follow-up relative to controls. In the systematic review, 7 cohort studies met inclusion criteria. After aggregating results with the Finnish cohort, retired soccer players appeared to have a lower risk of depression (summary risk ratio: 0.71 [0.54, 0.93]) relative to general population controls, while the rate of suicide was statistically the same across groups (0.70 [0.40, 1.23]). Past participation in American football seemed to be associated with some protection against suicide (0.58 [0.43, 0.80]) but there were insufficient studies of depression in this sport to facilitate aggregation. The aggregation of results from the soccer and American football studies showed directionally consistent relationships and there was no indication of inter-study heterogeneity (I2 = 0%). Interpretation Based on a small cluster of studies exclusively comprising men, retired soccer players had a lower rate of later depression and former American football players had a lower risk of suicide relative to comparator groups. Whether these findings are generalisable to women requires testing. Funding The preparation of this manuscript was unfunded.
Physical activity and academic performance are positively associated, but the direction of the association is poorly understood. This longitudinal study examined the direction and magnitude of the associations between leisure-time physical activity and academic performance throughout adolescence and young adulthood. The participants were Finnish twins (from 2,859 to 4,190 individuals/study wave) and their families. In a cross-lagged path model, higher academic performance at ages 12, 14 and 17 predicted higher leisure-time physical activity at subsequent time-points (standardized path coefficient at age 14: 0.07 (p<0.001), age 17: 0.12 (p<0.001) and age 24: 0.06 (p<0.05)), whereas physical activity did not predict future academic performance. A cross-lagged model of co-twin differences suggested that academic performance and subsequent physical activity were not associated due to the environmental factors shared by co-twins. Our findings suggest that better academic performance in adolescence modestly predicts more frequent leisure-time physical activity in late adolescence and young adulthood.
Background: Both genetic and environmental influences have been shown to contribute to the association between physical activity and overall academic performance. The authors examined whether leisure-time physical activity (LTPA) shares genetic and environmental variances between spelling, essay writing, reading aloud, reading comprehension, and mathematics in early adolescence. Moreover, they investigated whether genetic polymorphisms associated with physical activity behavior affect these academic skills. Methods: Participants were 12-year-old Finnish twins (n = 4356–4370 twins/academic skill, 49% girls). Academic skills were assessed by teachers, and LTPA was self-reported. Polygenic scores for physical activity behavior were constructed from the UK Biobank. Quantitative genetic modeling and linear regression models were used to analyze the data. Results: The trait correlations between LTPA and academic skills were significant but weak (r = .05–.08). The highest trait correlation was found between LTPA and mathematics. A significant genetic correlation was revealed between LTPA and essay writing (rA = .14). Regarding polygenic scores of physical activity, the highest correlations were found with reading comprehension, spelling, and essay writing, but these results only approached statistical significance (P values = .09–.15). Conclusions: The authors’ results suggest that reading and writing are the academic skills that most likely share a common genetic background with LTPA.
Background Adolescent substance use is associated with lower educational achievement but the directionality of the association remains uncertain. We analyzed data on drinking, smoking and educational achievement to study the associations between substance use and education from early adolescence to young adulthood. Methods Longitudinal data from four time points (ages 12, 14, 17, and 19–27 years) from a population-based cohort study of Finnish twin individuals were used to estimate bivariate cross-lagged path models for substance use and educational achievement, adjusting for sex, parental covariates, and adolescent externalizing behavior. A total of 4761 individuals (49.4% females) were included in the analyses. Educational achievement was assessed with teacher-reported grade point average at ages 12 and 14, and with self-reported student status and completed education at age 17 and in young adulthood. From self-reported questionnaire items, frequency of any drinking, frequency of drinking to intoxication, any smoking and daily smoking were analyzed. Results Alcohol use and smoking behaviors at ages 12 and 14 predicted lower educational achievement at later time points even after previous achievement and confounding factors were taken into account. Lower school achievement in adolescence predicted a higher likelihood of engaging in smoking behaviors but did not predict later alcohol use. Higher educational attainment at age 17 predicted more frequent drinking in young adulthood. Conclusions Adolescent drinking behaviors are associated with lower future educational achievement independently of prior achievement, whereas smoking both predicts and is predicted by lower achievement. Early substance use indexes elevated risk for poor educational outcomes.
In contrast to many phenotypes that have been studied using twin designs, substance use shows considerable evidence of environmental influence. Accordingly, specifying the relevant environments and understanding the nature of their effects is an important research priority. Twin studies also have demonstrated that the importance of genetic and environmental influences varies across development for a variety of behavioral outcomes, including substance use. Here, we report analyses exploring moderating effects associated with parenting and peer characteristics on adolescent smoking and drinking, measured at ages 14 and 17. We find significant evidence of moderating effects associated with two dimensions of parenting (parental monitoring and time spent in activities with parents) on adolescent smoking, measured at two time points across development, but no moderating effects on adolescent drinking. Genetic influences on smoking increased, and common environmental effects decreased, as adolescents reported less parental monitoring and spending more time with their parents. Conversely, we find evidence that adolescent drinking is more strongly influenced by peer characteristics. The importance of genetic predispositions was increased among adolescents who reported more friends who used alcohol. These analyses illustrate the importance of incorporating measured aspects of the environment into genetically informative twin models to begin to understand how specific environments are related to various outcomes. Furthermore, they illustrate the importance of using a developmental perspective to understand how specific influences may vary across different ages, and across different phenotypes.
We examined longitudinal associations between individual leisure activities (television viewing, video viewing, computer games, listening to music, board games, musical instrument playing, reading, arts, crafts, socializing, clubs or scouts, sports, outdoor activities) and being overweight using logistic regression and latent class analysis in a cohort of Finnish twins responding to self-report questionnaires at 11–12 (N = 5184), 14, and 17 years. We also studied activity patterns (“Active and sociable”, “Active but less sociable”, “Passive but sociable”, “Passive and solitary”) thought to represent different lifestyles. Among boys, activity patterns did not predict becoming overweight, but sports and playing an instrument reduced the risk and arts and listening to music increased it. Among girls, few individual leisure activities predicted becoming overweight. However, girls in the “Passive and solitary” cluster carried the greatest risk of becoming overweight in late adolescence. Studying leisure activities related to overweight may help focus specific interventions on high risk groups.
Background. Overweight in children and adolescents has reached dimensions of a global epidemic during recent years. Simultaneously, information and communication technology use has rapidly increased. Methods. A population-based sample of Finnish twins born in 1983–1987 (N = 4098) was assessed by self-report questionnaires at 17 y during 2000–2005. The association of overweight (defined by Cole's BMI-for-age cut-offs) with computer and cell phone use and ownership was analyzed by logistic regression and their association with BMI by linear regression models. The effect of twinship was taken into account by correcting for clustered sampling of families. All models were adjusted for gender, physical exercise, and parents' education and occupational class. Results. The proportion of adolescents who did not have a computer at home decreased from 18% to 8% from 2000 to 2005. Compared to them, having a home computer (without an Internet connection) was associated with a higher risk of overweight (odds ratio 2.3, 95% CI 1.4 to 3.8) and BMI (beta coefficient 0.57, 95% CI 0.15 to 0.98). However, having a computer with an Internet connection was not associated with weight status. Belonging to the highest quintile (OR 1.8 95% CI 1.2 to 2.8) and second-highest quintile (OR 1.6 95% CI 1.1 to 2.4) of weekly computer use was positively associated with overweight. The proportion of adolescents without a personal cell phone decreased from 12% to 1% across 2000 to 2005. There was a positive linear trend of increasing monthly phone bill with BMI (beta 0.18, 95% CI 0.06 to 0.30), but the association of a cell phone bill with overweight was very weak. Conclusion. Time spent using a home computer was associated with an increased risk of overweight. Cell phone use correlated weakly with BMI. Increasing use of information and communication technology may be related to the obesity epidemic among adolescents.
ntroduction : Previous longitudinal research suggests that motor proficiency in early life predicts physical activity in adulthood. Familial effects including genetic and environmental factors could explain the association, but no long-term follow-up studies have taken into account potential confounding by genetic and social family background. The present twin study investigated whether childhood motor skill development is associated with leisure-time physical activity levels in adulthood independent of family background. Methods : Altogether, 1550 twin pairs from the FinnTwin12 study and 1752 twin pairs from the FinnTwin16 study were included in the analysis. Childhood motor development was assessed by the parents _ report of whether one of the co-twins had been ahead of the other in different indicators of motor skill development in childhood. Leisure-time physical activity (MET I h I d j 1 ) was self-reported by the twins in young adulthood and adulthood. Statistical analyses included conditional and ordinary linear regression models within twin pairs. Results : Using all activity-discordant twin pairs, the within-pair difference in a sum score of motor development in childhood predicted the within-pair difference in the leisure-time physical activity level in young adulthood ( P G 0.001). Within specific motor development indicators, learning to stand unaided earlier in infancy predicted higher leisure-time MET values in young adulthood statistically significantly in both samples (FinnTwin12, P = 0.02; and FinnTwin16, P = 0.001) and also in the pooled data set of the FinnTwin12 and FinnTwin16 studies ( P G 0.001). Having been more agile than the co-twin as a child predicted higher leisure-time MET values up to adulthood ( P =0.03). Conclusions : More advanced childhood motor development is associated with higher leisure-time MET values in young adulthood at least partly independent of family background in both men and women.
Introduction. Physical activity and academic performance are believed to be associated. Though both traits are partially heritable, it remains unclear whether these traits also share a genetic and/or environmental background in common. We aimed to examine to what extent leisure-time physical activity and academic performance share genetic and environmental effects from early adolescence to young adulthood. Methods. Participants were Finnish twins (2543–2693 individuals/study wave) who reported their leisure-time physical activity at ages 12, 14, 17 and 24. Academic performance was assessed with teacher-reported grade point averages at ages 12 and 14 and by self-reported educational levels at ages 17 and 24. Bivariate quantitative genetic modeling at each age and between different ages was performed to decompose the trait correlation between academic performance and physical activity into genetic and environmental components. Results. The trait correlations between leisure-time physical activity and academic performance were positive, but modest at most (rtrait=0.08–0.22 in males, and 0.07–0.18 in females). The genetic correlations between leisure-time physical activity and academic performance were higher than the trait correlations (rA=0.17–0.43 in males, and 0.15–0.25 in females). Common genetic influences explained 43–100% of the trait correlations. Environmental influences shared by co-twins between leisure-time physical activity and academic performance were also correlated (rC=0.27–0.54 in males, and 0.21–0.69 in females) explaining 41–100% of the trait correlations. Unique environmental influences were correlated only in females (rE=0.10–0.15). Conclusion. Both common genetic background and shared family environment (i.e., familial background) partially account for the associations observed between leisure-time physical activity and academic performance. However, the estimates vary in magnitude by age.
Abstract Exosomes participate in intercellular messaging by transporting bioactive lipid-, protein- and RNA-molecules and -complexes. The contents of the exosomes reflect the physiological status of an individual making exosomes promising targets for biomarker analyses. In the present study we extracted exosome microRNAs (exomiRs) from serum samples of premenopausal women (n = 8) and monozygotic postmenopausal twins (n = 10 female pairs), discordant for the use of estrogenic hormone replacement therapy (HRT), in order to see whether the age or/and the use of HRT associates with exomiR content. A total of 241 exomiRs were detected by next generation sequencing, 10 showing age, 14 HRT and 10 age +HRT -related differences. When comparing the groups, differentially expressed miRs were predicted to affect cell proliferation processes showing inactivation with younger age and HRT usage. MiR-106-5p, -148a-3p, -27-3p, -126-5p, -28-3p and -30a-5p were significantly associated with serum 17β-estradiol. MiRs formed two hierarchical clusters being indicative of positive or negative health outcomes involving associations with body composition, serum 17β-estradiol, fat-, glucose- and inflammatory markers. Circulating exomiR clusters, obtained by NGS, could be used as indicators of metabolic and inflammatory status affected by hormonal changes at menopause. Furthermore, the individual effects of HRT-usage could be evaluated based on the serum exomiR signature.
We analyzed how the effects of genetic and environmental factors on the perceptions of family interaction change from early to late adolescence. The data were collected by postal surveys on Finnish twins (N = 4808) at 12, 14 and 17 years of age and analyzed using genetic twin modeling. Additive genetic factors explained a modest share of the variation in perceived relational support (a2 = 0.30 in boys and 0.18 in girls) and relational tensions (a2 = 0.13 and 0.14, respectively) at 12 years of age, with the proportions becoming larger through 17 years of age (a2 = 0.53 in boys and 0.49 in girls for relational support; a2 = 0.35 in boys and 0.33 in girls for relational tensions). Simultaneously, the role of environment shared by co-twins decreased. These findings suggest that the associations between perceived family interaction and other factors in adulthood should be interpreted with caution, because they partly reflect genetic background, whereas in childhood, they may provide more reliable information on parental characteristics.
Conflicting reports exist on the direction of the relationship between social anxiety (SA) and alcohol/cigarette use (AU/CU) and alcohol/nicotine dependence (AD/ND), with both positive and negative associations reported. A prospective, longitudinal sample of Finnish twins (n = 1,906) was used to test potential explanations for these discrepancies. Specifically, this study used peer, parent, and teacher ratings of SA, and a clinical interview screening item for social anxiety disorder (SAD-Sc) to examine associations between SA and AU/CU and AD/ND from early adolescence into young adulthood. Peer-rated SA was negatively associated with AU, CU, and AD from age 14 through age 22, implying a protective effect (β = −0.01 to −.03). Teacher- and parent-rated SA associations were in the same directions but weaker or nonsignificant, indicating that aspects of SA that are recognizable by peers may be most relevant to AU/CU. Self-reported SAD-Sc was also negatively associated with AU, but positively associated with AD symptoms in young adulthood (β = 0.38). Our findings partially support the existence of different associations between SA and AU versus AD, but only in the context of SAD-Sc rather than trait SA. Neither trait SA nor SAD-Sc significantly predicted ND symptoms, although SAD-Sc was associated with both cigarette abstinence and daily smoking. These findings suggest that adolescent SA is modestly associated with lower AU/CU, although there may be some individuals with more severe SA who develop alcohol problems later in life. There was little evidence of a common underlying liability contributing to both SA and alcohol/cigarette use. (PsycINFO Database Record (c) 2016 APA, all rights reserved)
Background Although there is growing evidence that former professional athletes from sports characterised by repetitive head impact subsequently experience an elevated risk of dementia, the occurrence of this disorder in retired amateurs, who represent a larger population, is uncertain. The present meta-analysis integrates new results from individual-participant analyses of a cohort study of former amateur contact sports participants into a systematic review of existing studies of retired professionals and amateurs. Methods The cohort study comprised 2005 male retired amateur athletes who had competed internationally for Finland (1920–1965) and a general population comparison group of 1386 age-equivalent men. Dementia occurrence was ascertained from linked national mortality and hospital records. For the PROSPERO-registered (CRD42022352780) systematic review, we searched PubMed and Embase from their inception to April 2023, including cohort studies published in English that reported standard estimates of association and variance. Study-specific estimates were aggregated using random-effect meta-analysis. An adapted Cochrane Risk of Bias Tool was used to assess study quality. Findings In the cohort study, up to 46 years of health surveillance of 3391 men gave rise to 406 dementia cases (265 Alzheimer’s disease). After adjustment for covariates, former boxers experienced elevated rates of dementia (hazard ratio: 3.60 [95% CI 2.46, 5.28]) and Alzheimer’s disease (4.10 [2.55, 6.61]) relative to general population controls. Associations were of lower magnitude in retired wrestlers (dementia: 1.51 [0.98, 2.34]; Alzheimer’s disease: 2.11 [1.28, 3.48]) and soccer players (dementia: 1.55 [1.00, 2.41]; Alzheimer’s disease: 2.07 [1.23, 3.46]), with some estimates including unity. The systematic review identified 827 potentially eligible published articles, of which 9 met our inclusion criteria. These few retrieved studies all sampled men and the majority were of moderate quality. In sport-specific analyses according to playing level, there was a marked difference in dementia rates in onetime professional American football players (2 studies; summary risk ratio: 2.96 [95% CI 1.66, 5.30]) relative to amateurs in whom there was no suggestion of an association (2 studies; 0.90 [0.52, 1.56]). For soccer players, while dementia occurrence was raised in both erstwhile professionals (2 studies; 3.61 [2.92, 4.45]) and amateurs (1 study; 1.60 [1.11, 2.30]) there was again a suggestion of a risk differential. The only studies of boxers comprised former amateurs in whom there was a tripling in the rates of dementia (2 studies; 3.14 [95% CI 1.72, 5.74]) and Alzheimer’s disease (2 studies; 3.07 [1.01, 9.38]) at follow-up compared to controls. Interpretation Based on a small number of studies exclusively sampling men, former amateur participants in soccer, boxing, and wrestling appeared to experience an elevated risk of dementia relative to the general population. Where data allowed comparison, there was a suggestion that risks were greater amongst retired professionals relative to amateurs in the sports of soccer and American football. Whether these findings are generalisable to the contact sports not featured, and to women, warrants examination. Funding This work was unfunded.
Abstract: In order to further understand why depressive symptoms are associated with negative goal appraisals, the present study examined the genetic and environmental correlations and interactions between depressive symptoms and career-related goal appraisals. A total of 1,240 Finnish twins aged 21–26 years completed a questionnaire containing items on the appraisal of their career goals along five dimensions: importance, progress, effort, strain, and self-efficacy. In the same questionnaire, the 10-item General Behavior Inven- tory assessed depressive symptoms. Structural equation modeling was used to evaluate the genetic and environmental correlations and gene–environment interactions between the career-goal appraisals and depressive symptoms. Associations were identified, and were attributed to environmental factors. Of the career-related goal appraisals, the shared environmental component was of a higher magnitude for the dimension of strain among the depressed compared with non-depressed subjects. The results indicate that the interplay between depressive symptoms and negative career-related goal appraisals is significantly affected by environmental factors, and thus possibly susceptible to targeted interventions.
Depressive symptoms and alcohol use are frequently positively associated during adolescence. This study aimed to assess the heritability of each phenotype across adolescence; to assess potential shared liabilities; to examine changes in the nature of shared liabilities across adolescence; and to investigate potential causal relationships between depressive symptoms and alcohol use. We studied a longitudinally assessed sample of adolescent Finnish twins (N = 1,282) to test hypotheses about genetic and environmental influences on these phenotypes within and across ages, using data from assessments at ages 12, 14, and 17.5 years. The heritability of depressive symptoms is consistent across adolescence (~40–50%), with contributions from common and unique environmental factors. The heritability of alcohol use varies across time (a2 = .25–.44), and age 14 alcohol use is heavily influenced by shared environmental factors. Genetic attenuation and innovation were observed across waves. Modest to moderate genetic (rA = .26–.59) and environmental (rC = .30–.63) correlations between phenotypes exist at all ages, but decrease over time. Tests for causal relationships between traits differed across ages and sexes. Intrapair MZ difference tests provided evidence for reciprocal causation in girls at ages 14 and 17.5. Formal causal models suggested significant causal relationships between the variables in both boys and girls. The association between depressive symptoms and alcohol use during adolescence is likely due to a combination of shared genetic and environmental influences and causal influences. These influences are also temporally dynamic, complicating efforts to understand factors contributing to the relationship between these outcomes.
Background Developmental relationships between tobacco use and suicide-related behaviors (SRB) remain unclear. Our objective was to investigate the longitudinal associations of tobacco use in adolescence and SRB in adulthood. Methods Using a prospective design, we examined whether tobacco use in adolescence is associated with SRB (intentional self-injury, suicide ideation) in young adulthood in a population-based sample of 1330 twins (626 males, 704 females). The baseline and follow-up data were collected by professionally administered semi-structured poly-diagnostic interviews at ages 14 and 22, respectively. Results After adjusting for multiple potential confounders, those who reported early-onset of regular tobacco use had a significantly increased risk for intentional self-injury, such as cutting or burning, at age 22 (adjusted odds ratio [AOR] 4.57, 95% CI 1.93–10.8) in comparison to those who had not at all initiated tobacco use. Also, daily cigarette smoking at baseline was associated with future intentional self-injury (AOR 4.45, 95% CI 2.04–9.70). Early-onset tobacco use was associated with suicidal ideation in females (AOR 3.69, 95% CI 1.56–8.72) but not in males. Considering any SRB, baseline daily smokers (AOR 2.13, 95% CI 1.12–4.07) and females with early onset of regular tobacco use (AOR 3.97, 95% CI 1.73–9.13) had an increased likelihood. Within-family analyses among twin pairs discordant for exposure and outcome controlling for familial confounds showed similar, albeit statistically non-significant, associations. Conclusion Early-onset tobacco use in adolescence is longitudinally associated with SRB (intentional self-injury and/or suicide ideation) in young adulthood, particularly among females. Further investigation may reveal whether this association has implications for prevention of SRB in adolescence and young adulthood.
Modestly prevalent in the general population (~ 4%), but highly prevalent in prison populations (> 40%), the diagnosis of antisocial personality disorder (ASPD) involves aggression as one of several possible criteria. Using multiple informants, we aimed to determine if general aggression, as well as direct and indirect subtypes, assessed in early adolescence (ages 12, 14) predict young adulthood ASPD in a population-based sample. Using data from a Finnish population-based longitudinal twin cohort study with psychiatric interviews available at age 22 (N = 1347), we obtained DSM-IV-based ASPD diagnoses. Aggression measures from ages 12 (parental and teacher ratings) and 14 (teacher, self, and co-twin ratings) were used to calculate odds ratios (OR) of ASPD from logistic regression models and the area under the curve (AUC) from receiver operating characteristic curve analysis. Analyses were adjusted for sex, age, and family structure. All informants’ aggression ratings were significant (p < 0.05) predictors of ASPD (OR range 1.3–1.8; AUC range 0.65–0.72). Correlations between informants ranged from 0.13 to 0.33. Models including two or more aggression ratings, particularly age 14 teacher and self ratings, more accurately predicted ASPD (AUC: 0.80; 95% confidence interval 0.73–0.87). Direct aggression rated by all informants significantly predicted ASPD (OR range 1.4–1.9), whereas only self-rated indirect aggression was significantly associated with ASPD (OR = 1.4). Across different informants, general and direct aggression at ages 12 and 14 predicted ASPD in a population-based sample. Psychiatric, social, and parenting interventions for ASPD prevention should focus on children and adolescents with high aggression levels, with an aim to gather information from multiple informants.
Abstract Polygenic risk scores (PRS) for breast cancer have potential to improve risk prediction, but there is limited information on their utility in various clinical situations. Here we show that among 122,978 women in the FinnGen study with 8401 breast cancer cases, the PRS modifies the breast cancer risk of two high-impact frameshift risk variants. Similarly, we show that after the breast cancer diagnosis, individuals with elevated PRS have an elevated risk of developing contralateral breast cancer, and that the PRS can considerably improve risk assessment among their female first-degree relatives. In more detail, women with the c.1592delT variant in PALB2 (242-fold enrichment in Finland, 336 carriers) and an average PRS (10–90th percentile) have a lifetime risk of breast cancer at 55% (95% CI 49–61%), which increases to 84% (71–97%) with a high PRS ( > 90th percentile), and decreases to 49% (30–68%) with a low PRS ( < 10th percentile). Similarly, for c.1100delC in CHEK2 (3.7–fold enrichment; 1648 carriers), the respective lifetime risks are 29% (27–32%), 59% (52–66%), and 9% (5–14%). The PRS also refines the risk assessment of women with first-degree relatives diagnosed with breast cancer, particularly among women with positive family history of early-onset breast cancer. Here we demonstrate the opportunities for a comprehensive way of assessing genetic risk in the general population, in breast cancer patients, and in unaffected family members.
Abstract Purpose: Polygenic risk scores (PRS) summarize genome-wide genotype data into a single variable that produces an individual-level risk score for genetic liability. PRS has been used for prediction of chronic diseases and some risk factors. As PRS has been studied less for physical activity (PA), we constructed PRS for PA and studied how much variation in PA can be explained by this PRS in independent population samples. Methods: We calculated PRS for self-reported and objectively measured PA using UK Biobank genome-wide association study summary statistics, and analyzed how much of the variation in self-reported (MET-hours per day) and measured (steps and moderate-to-vigorous PA minutes per day) PA could be accounted for by the PRS in the Finnish Twin Cohorts (FTC; N = 759–11,528) and the Northern Finland Birth Cohort 1966 (NFBC1966; N = 3263–4061). Objective measurement of PA was done with wrist-worn accelerometer in UK Biobank and NFBC1966 studies, and with hip-worn accelerometer in the FTC. Results: The PRS accounted from 0.07% to 1.44% of the variation (R2) in the self-reported and objectively measured PA volumes (P value range = 0.023 to <0.0001) in the FTC and NFBC1966. For both self-reported and objectively measured PA, individuals in the highest PRS deciles had significantly (11%–28%) higher PA volumes compared with the lowest PRS deciles (P value range = 0.017 to <0.0001). Conclusions: PA is a multifactorial phenotype, and the PRS constructed based on UK Biobank results accounted for statistically significant but overall small proportion of the variation in PA in the Finnish cohorts. Using identical methods to assess PA and including less common and rare variants in the construction of PRS may increase the proportion of PA explained by the PRS.
DNA microarrays and RNAseq are complementary methods for studying RNA molecules. Current computational methods to determine alternative exon usage (AEU) using such data require impractical visual inspection and still yield high false-positive rates. Integrated Gene and Exon Model of Splicing (iGEMS) adapts a gene-level residuals model with a gene size adjusted false discovery rate and exon-level analysis to circumvent these limitations. iGEMS was applied to two new DNA microarray datasets, including the high coverage Human Transcriptome Arrays 2.0 and performance was validated using RT-qPCR. First, AEU was studied in adipocytes treated with (n = 9) or without (n = 8) the anti-diabetes drug, rosiglitazone. iGEMS identified 555 genes with AEU, and robust verification by RT-qPCR (∼90%). Second, in a three-way human tissue comparison (muscle, adipose and blood, n = 41) iGEMS identified 4421 genes with at least one AEU event, with excellent RT-qPCR verification (95%, n = 22). Importantly, iGEMS identi- fied a variety of AEU events, including 3 UTR extension, as well as exon inclusion/exclusion impacting on protein kinase and extracellular matrix domains. In conclusion, iGEMS is a robust method for identi- fication of AEU while the variety of exon usage between human tissues is 5–10 times more prevalent than reported by the Genotype-Tissue Expression consortium using RNA sequencing.
Aims/hypothesis: Existing studies suggest that decreased branched-chain amino acid (BCAA) catabolism and thus elevated levels in blood are associated with metabolic disturbances. Based on such information, we have developed a hypothesis how BCAA degradation mechanistically connects to tricarboxylic acid cycle, intramyocellular lipid storage, and oxidation, thus allowing more efficient mitochondrial energy production from lipids as well as providing better metabolic health. We analyzed whether data from aged Finnish men are in line with our mechanistic hypothesis linking BCAA catabolism and metabolic disturbances. Methods: Older Finnish men enriched with individuals having been athletes in young adulthood (n = 593; mean age 72.6 ± 5.9 years) responded to questionnaires, participated in a clinical examination including assessment of body composition with bioimpedance and gave fasting blood samples for various analytes as well as participated in a 2-h 75 g oral glucose tolerance test. Metabolomics measurements from serum included BCAAs (isoleucine, leucine, and valine). Results: Out of the 593 participants, 59 had previously known type 2 diabetes, further 67 had screen-detected type 2 diabetes, 127 impaired glucose tolerance, and 125 impaired fasting glucose, while 214 had normal glucose regulation and one had missing glucose tolerance information. There were group differences in all of the BCAA concentrations (p ≤ 0.005 for all BCAAs), such that those with normal glucose tolerance had the lowest and those with diabetes mellitus had the highest BCAA concentrations. All BCAA levels correlated positively with body fat percentage (r = 0.29–0.34, p < 0.0001 for all). Expected associations with high BCAA concentrations and unfavorable metabolic profile indicators from metabolomics analysis were found. Except for glucose concentrations, the associations were stronger with isoleucine and leucine than with valine. Conclusion/interpretation: The findings provided further support for our hypothesis by strengthening the idea that the efficiency of BCAA catabolism may be mechanistically involved in the regulation of fat oxidation, thus affecting the levels of metabolic disease risk factors.
Ageing is associated with a decline in muscle mass and strength leading to increased physical dependency in old age. Postmenopausal women experience a greater decline than men of similar age in parallel with the decrease in female sex steroid hormone production. We recruited six monozygous female twin pairs (55–59 years old) where only one twin pair was on hormone replacement therapy (HRT use = 7.8 ± 4.3 years) to investigate the association of HRT with the cytoplasmic volume supported by individual myonuclei (myonuclear domain (MND) size,) together with specific force at the single fibre level. HRT use was associated with a significantly smaller (∼27%; P < 0.05) mean MND size in muscle fibres expressing the type I but not the IIa myosin heavy chain (MyHC) isoform. In comparison to non-users, higher specific force was recorded in HRT users both in muscle fibres expressing type I (∼27%; P < 0.05) and type IIa (∼23%; P < 0.05) MyHC isoforms. These differences were fibre-type dependent, i.e. the higher specific force in fast-twitch muscle fibres was primarily caused by higher force per cross-bridge while slow-twitch fibres relied on both a higher number and force per cross-bridge. HRT use had no effect on fibre cross-sectional area (CSA), velocity of unloaded shortening (V0) and relative proportion of MyHC isoforms. In conclusion, HRT appears to have significant positive effects on both regulation of muscle contraction and myonuclei organization in postmenopausal women.
Background Characterizing aggregate genetic risk for alcohol misuse and identifying variants involved in gene-by-environment (G × E) interaction effects has so far been a major challenge. We hypothesized that functional genomic information could be used to enhance detection of polygenic signal underlying alcohol misuse and to prioritize identification of single nucleotide polymorphisms (SNPs) most likely to exhibit G × E effects. Methods We examined these questions in the young adult FinnTwin12 sample (n = 1,170). We used genomewide association estimates from an independent sample to derive 2 types of polygenic scores for alcohol problems in FinnTwin12. Genomewide polygenic scores included all SNPs surpassing a designated p-value threshold. DNase polygenic scores were a subset of the genomewide polygenic scores including only variants in DNase I hypersensitive sites (DHSs), which are open chromatin marks likely to index regions with a regulatory function. We conducted parallel analyses using height as a nonpsychiatric model phenotype to evaluate the consistency of effects. For the G × E analyses, we examined whether SNPs in DHSs were overrepresented among SNPs demonstrating significant G × E effects in an interaction between romantic relationship status and intoxication frequency. Results Contrary to our expectations, we found that DNase polygenic scores were not more strongly predictive of alcohol problems than conventional polygenic scores. However, variants in DNase polygenic scores had per-SNP effects that were up to 1.4 times larger than variants in conventional polygenic scores. This same pattern of effects was also observed in supplementary analyses with height. In G × E models, SNPs in DHSs were modestly overrepresented among SNPs with significant interaction effects for intoxication frequency. Conclusions These findings highlight the potential utility of integrating functional genomic annotation information to increase the signal-to-noise ratio in polygenic scores and identify genetic variants that may be most susceptible to environmental modification.
Global emphasis on enhancing prevention and treatment strategies necessitates an increased understanding of the biological mechanisms of psychopathology. Plasma proteomics is a powerful tool that has been applied in the context of specific mental disorders for biomarker identification. The p-factor, also known as the “general psychopathology factor”, is a concept in psychopathology suggesting that there is a common underlying factor that contributes to the development of various forms of mental disorders. It has been proposed that the p-factor can be used to understand the overall mental health status of an individual. Here, we aimed to discover plasma proteins associated with the p-factor in 775 young adults in the FinnTwin12 cohort. Using liquid chromatography–tandem mass spectrometry, 13 proteins with a significant connection with the p-factor were identified, 8 of which were linked to epidermal growth factor receptor (EGFR) signaling. This exploratory study provides new insight into biological alterations associated with mental health status in young adults.
Abstract Copy number variants (CNVs) are associated with syndromic and severe neurological and psychiatric disorders (SNPDs), such as intellectual disability, epilepsy, schizophrenia, and bipolar disorder. Although considered high-impact, CNVs are also observed in the general population. This presents a diagnostic challenge in evaluating their clinical significance. To estimate the phenotypic differences between CNV carriers and non-carriers regarding general health and well-being, we compared the impact of SNPD-associated CNVs on health, cognition, and socioeconomic phenotypes to the impact of three genome-wide polygenic risk score (PRS) in two Finnish cohorts (FINRISK, n = 23,053 and NFBC1966, n = 4895). The focus was on CNV carriers and PRS extremes who do not have an SNPD diagnosis. We identified high-risk CNVs (DECIPHER CNVs, risk gene deletions, or large [>1 Mb] CNVs) in 744 study participants (2.66%), 36 (4.8%) of whom had a diagnosed SNPD. In the remaining 708 unaffected carriers, we observed lower educational attainment (EA; OR = 0.77 [95% CI 0.66–0.89]) and lower household income (OR = 0.77 [0.66–0.89]). Income-associated CNVs also lowered household income (OR = 0.50 [0.38–0.66]), and CNVs with medical consequences lowered subjective health (OR = 0.48 [0.32–0.72]). The impact of PRSs was broader. At the lowest extreme of PRS for EA, we observed lower EA (OR = 0.31 [0.26–0.37]), lower-income (OR = 0.66 [0.57–0.77]), lower subjective health (OR = 0.72 [0.61–0.83]), and increased mortality (Cox’s HR = 1.55 [1.21–1.98]). PRS for intelligence had a similar impact, whereas PRS for schizophrenia did not affect these traits. We conclude that the majority of working-age individuals carrying high-risk CNVs without SNPD diagnosis have a modest impact on morbidity and mortality, as well as the limited impact on income and educational attainment, compared to individuals at the extreme end of common genetic variation. Our findings highlight that the contribution of traditional high-risk variants such as CNVs should be analyzed in a broader genetic context, rather than evaluated in isolation.
Abstract Background: Lower birthweight is associated with increased susceptibility to cardiometabolic diseases in adulthood, but the underlying molecular pathways are incompletely understood. We examined associations of birthweight with a comprehensive metabolic profile measured in adolescents and adults. Methods: High-throughput nuclear magnetic resonance metabolomics and biochemical assays were used to quantify 87 circulating metabolic measures in seven cohorts from Finland and the UK, comprising altogether 18 288 individuals (mean age 26 years, range 15–75). Metabolic associations with birthweight were assessed by linear regression models adjusted for sex, gestational age and age at blood sampling. The metabolic associations with birthweight were compared with the corresponding associations with adult body mass index (BMI). Results: Lower birthweight adjusted for gestational age was adversely associated with cardiometabolic biomarkers, including lipoprotein subclasses, fatty acids, amino acids and markers of inflammation and impaired liver function (P < 0.0015 for 46 measures). Associations were consistent across cohorts with different ages at metabolic profiling, but the magnitudes were weak. The pattern of metabolic deviations associated with lower birthweight resembled the metabolic signature of higher adult BMI (R2 = 0.77) assessed at the same time as the metabolic profiling. The resemblance indicated that 1 kg lower birthweight is associated with similar metabolic aberrations as caused by 0.92 units higher BMI in adulthood. Conclusions: Lower birthweight adjusted for gestational age is associated with adverse biomarker aberrations across multiple metabolic pathways. Coherent metabolic signatures between lower birthweight and higher adult adiposity suggest that shared molecular pathways may potentially underpin the metabolic deviations. However, the magnitudes of metabolic associations with birthweight are modest in comparison to the effects of adiposity, implying that birthweight is only a weak indicator of the metabolic risk profile in adulthood.
We examine whether parental externalizing behavior has an indirect effect on adolescent externalizing behavior via elevations in life events, and whether this indirect effect is further qualified by an interaction between life events and adolescents’ GABRA2 genotype (rs279871). We use data from 2 samples: the Child Development Project (CDP; n = 324) and FinnTwin12 (n = 802). In CDP, repeated measures of life events, mother-reported adolescent externalizing, and teacher-reported adolescent externalizing were used. In FinnTwin12, life events and externalizing were assessed at age 14. Parental externalizing was indexed by measures of antisocial behavior and alcohol problems or alcohol dependence symptoms in both samples. In CDP, parental externalizing was associated with more life events, and the association between life events and subsequent adolescent externalizing varied as a function of GABRA2 genotype (p ≤ .05). The association between life events and subsequent adolescent externalizing was stronger for adolescents with 0 copies of the G minor allele compared to those with 1 or 2 copies of the minor allele. Parallel moderation trends were observed in FinnTwin12 (p ≤ .11). The discussion focuses on how the strength of intergenerational pathways for externalizing psychopathology may differ as a function of adolescent-level individual differences.