Finnish Twin Cohort Study Research Articles

Measurement invariance of the Center for Epidemiological Studies-Depression scale and associations with genetic risk in older adults.

As populations are aging, it needs to be ensured that valid depression rating scales are available across old adulthood. Center for Epidemiological Studies-Depression scale (CES-D) is a common depression rating scale, however, few studies have assessed its validity in individuals with age over 90 and/or cognitive impairment. We examined the factor structures of 20-, 15-, and 8-item CES-D scales, their measurement invariance for age and cognition, and associations with genetic risk of depression. Participants were from a population-based older Finnish Twin Cohort study including 71-79-year-olds from the MEMTWIN II (n = 1034 for exploratory and n = 664 for confirmatory factor analyses) and 90+ year-olds from the NONAGINTA (n = 134, confirmatory factor analyses) sub-studies. Associations of polygenic risk score of major depressive disorder (MDD-PRS) with CES-D scales were examined in MEMTWIN II. Exploratory factor analyses (n = 1034) suggested four- (CES-D 20) and three-factor (CES-D 8) structures and these models fit well in confirmatory analyses (n = 664). Unidimensional models had good (CES-D 15 & 20) or fair fit (CES-D 8). Results supported scalar invariance of all CES-D versions for age and cognitive status. Higher MDD-PRS was associated with more depressive symptoms in different CES-D versions. Different CES-D versions are adequate for measuring depressive symptoms across age groups and cognitive spectrum in old age. Genetic risk of depression predicts depressive symptoms even in old age.

TWINGEN: protocol for an observational clinical biobank recall and biomarker cohort study to identify Finnish individuals with high risk of Alzheimer’s disease

IntroductionA better understanding of the earliest stages of Alzheimer’s disease (AD) could expedite the development or administration of treatments. Large population biobanks hold the promise to identify individuals at an...

Longitudinal leisure-time physical activity profiles throughout adulthood and related characteristics: a 36-year follow-up study of the older Finnish Twin Cohort

BackgroundPersonalized interventions aiming to increase physical activity in individuals are effective. However, from a public health perspective, it would be important to stimulate physical activity in larger groups of people who share the vulnerability to be physically inactive throughout adulthood. To find these high-risk groups, we identified 36-year leisure-time physical activity profiles from young adulthood to late midlife in females and males. Moreover, we uncovered which anthropometric-, demographic-, lifestyle-, and health-related characteristics were associated with these physical activity profiles.MethodsWe included 2,778 females and 1,938 males from the population-based older Finnish Twin Cohort Study, who responded to health and behavior surveys at the mean ages of 24, 30, 40 and 60. Latent profile analysis was used to identify longitudinal leisure-time physical activity profiles.ResultsWe found five longitudinal leisure-time physical activity profiles for both females and males. Females’ profiles were: 1) Low increasing moderate (29%), 2) Moderate stable (23%), 3) Very low increasing low (20%), 4) Low stable (20%) and 5) High increasing high (9%). Males’ profiles were: 1) Low increasing moderate (29%), 2) Low stable very low (26%), 3) Moderate decreasing low (21%), 4) High fluctuating high (17%) and 5) Very low stable (8%). In both females and males, lower leisure-time physical activity profiles were associated with lower education, higher body mass index, smoking, poorer perceived health, higher sedentary time, high blood pressure, and a higher risk for type 2 diabetes. Furthermore, lower leisure-time physical activity was linked to a higher risk of depression in females.ConclusionsWe found several longitudinal leisure-time physical activity profiles with unique changes in both sexes. Fewer profiles in females than in males remained or became low physically active during the 36-year follow-up. We observed that lower education, higher body mass index, and more smoking already in young adulthood were associated with low leisure-time physical activity profiles. However, the fact that several longitudinal profiles demonstrated a change in their physical activity behavior over time implies the potential for public health interventions to improve leisure-time physical activity levels.

Age-related macular degeneration discordance in monozygotic twin pairs.

To examine age-related macular degeneration (AMD) and retinal pigment epithelium (RPE)-Bruch's membrane (BrM) complex volume associations in monozygotic twin pairs. In this study, 106 elderly twins (53 twin pairs) from the Finnish Twin Cohort study were recruited. Each participant underwent dilated 35-degree digital colour fundus photography (CFP), and spectral domain optical coherence tomography (OCT) and replied to a structured study questionnaire. The CFPs were graded according to the Age-Related Eye Disease Study (AREDS) classification. The OCT images were segmented and volumetric data of the RPE-BrM complex volume was calculated with the Orion™ software. The worse eye according to AREDS classification was used for the analysis. Twenty-nine (55%) of the twin pairs were discordant with regard to AREDS classification. Fourteen (26%) pairs were discordant with one twin participant having AMD (AREDS 2-4) and the other being unaffected (AREDS 1). Four (8%) pairs had one twin participant with intermediate or late AMD (AREDS 3-4) versus the other being unaffected (AREDS 1). The within-pair polychoric correlation for AREDS was 0.605 (95% confidence interval 0.418-0.792). In multivariate analysis intermediate and late AMD as well as age associated with RPE-BrM complex volume. RPE-BrM complex volume showed a within twin pair correlation, r = 0.430 (95% confidence interval 0.172-0.688, p < 0.01). A substantial proportion of monozygotic twin pairs are discordant with regard to age-related macular degeneration phenotype. RPE-BrM complex volume associated with age and intermediate and late AMD.

Educational Attainment and Risk of All‐Cause Dementia, Vascular Dementia, and Alzheimer’s Disease – A Population‐Based Twin Study

AbstractBackgroundMost studies on the association between educational attainment and dementia have been conducted in unrelated individuals. Dementia‐discordant twin pairs can inform if the protective effect of education on dementia is evident when controlling for environmental and genetic effects. We investigated the association of educational attainment on all‐cause dementia, vascular dementia (VaD), and Alzheimer’s disease (AD) mortality in a population‐based sample of dizygotic (DZ) and monozygotic (MZ) pairs.MethodParticipants were from a population‐based longitudinal older Finnish Twin Cohort study with baseline questionnaire in 1975 (N = 29,784; mean age = 36.9±14.9years). Education was coded as &lt;12 years versus ≥12 years. Registry‐based cause of death data until year 2020 was based on the International Classification of Diseases. We ran individual‐level cox proportional hazard models with sex as a covariate and conditional within‐twin‐pair models for education predicting all‐cause dementia, VaD, and AD mortality. We report hazard ratios (HR) with 95% confidence intervals (CI).ResultIn individual‐level analyses higher education was associated with a decreased risk of all‐cause dementia (HR = .935, 95%CI = .934;.936, p&lt;.001) and VaD (HR = .638, 95%CI = .637;.640, p&lt;.001), but with an increased risk of AD (HR = 1.276, 95%CI = 1.275;1.277, p&lt;.001). In co‐twin analyses of discordant DZ and MZ twin pairs, co‐twins with higher education had lower – although non‐significant – risk of all‐cause dementia (N = 52, HR = .688, 95%CI = .319;1.481, p = .339) or AD (N = 36, HR = .600, 95%CI: .218;1.651, p = .323). Co‐twin analyses were not done for VaD due to small number of discordant pairs (N = 6).ConclusionThis large population‐based sample showed that higher education is related to lower risk of all‐cause dementia and VaD mortality. Unexpectedly, higher education was related to higher AD mortality, but discordant twin pair analyses were informative regarding this counterintuitive result. This case‐control design, controlling for genetic and environmental effects, did not support any causality from higher education to higher AD risk. Despite the large sample, twin pairs – especially MZ twins – discordant for dementia are rare. Meta‐ or mega‐analysis of multiple large twin studies is needed to clarify if secondary education is related to lower risk of dementia, VaD, and AD mortality when controlling for genetic effects.

Antecedents of episodic memory in the oldest‐old: a population‐based NONAGINTA study with 45‐years of follow‐up

AbstractBackgroundWe have established NONAGINTA – Memory and Health in 90‐year‐olds –study in a population‐based sample with 45 years of follow‐up. Our study is aimed to understand both, the antecedents of cognitive impairment and successful cognitive aging in the oldest‐old (90 years or older).MethodParticipants were nonagenarians from a population‐based longitudinal older Finnish Twin Cohort study with baseline questionnaire in 1975. Ongoing 90‐year‐old data collection included postal questionnaire and telephone administered cognitive testing. Episodic memory (EM) was measured with total words recalled in three trials of 10‐word list. Predictors of EM included cognitive, health‐related, and psychological factors. Self‐reported educational attainment, body mass index (BMI), physical activity (METhours/day), life satisfaction and neuroticism were measured in middle age (N = 55, age M = 46.2, SD = 1.7 years) and in old age (N = 59‐67, age M = 91.3, SD = 1.9 years). Semantic verbal fluency (number of animals in 1‐minute) and depressive symptoms (Center for Epidemiological Studies – Depression (CES‐D)) were measured only in old age. We used individual level linear regression models with age and sex as covariates and adjusted for family structure.ResultTo date, 67 individuals have cognitive data. On average, women (N = 36, M = 11.97, SD = 4.70) had better EM than men (N = 31, M = 11.10, SD = 4.74), but this difference was not statistically significant (p = 0.49). Better verbal fluency was significantly related to better EM (r = 0.34, p&lt;0.001). Compared to those with 6 years of education, those with 7‐11 years and those with 12 or more years of education had significantly better EM: 4.03 (95%CI: 1.27‐6.80) (p = 0.005) and 5.75 (95%CI: 3.75‐7.45) (p&lt;0.001) words more, respectively. Mean CES‐D was 12.3 (SD = 8.7) and 16% scored above the cut‐off for clinically significant depressive symptoms, however, depressive symptoms were not related to EM (p = 0.15). Middle age or old age BMI, physical activity, life satisfaction or neuroticism were not significantly related to EM (p’s &gt;0.32).ConclusionOur preliminary results suggest that cognitive, but not midlife or old age physical or psychological health‐related factors, are associated with episodic memory performance in nonagenarians. Good episodic memory goes hand in hand with good semantic fluency and cognitive benefits of early life educational attainment are still evident in nonagenarians.

Case‐control co‐twin study on the associations of dementia risk factors with episodic memory in nonagenarians

AbstractBackgroundSeveral risk and protective factors of dementia are known, but the importance of genetic and environmental influences and the antecedents of cognitive functioning in 90‐year‐olds are not well known. Genetic and environmental confounding can be controlled better by using family data compared to samples of unrelated individuals. We examined dementia risk factors in 90‐year‐olds by conducting a case‐control co‐twin study on the associations of physical and psychological well‐being with episodic memory (EM).MethodWe invited 90‐year‐old twins from a population‐based older Finnish Twin Cohort study to participate in the ongoing NONAGINTA –study that includes questionnaires (risk factors) and telephone interview (cognitive functioning). To date, eight full same‐sex pairs have cognitive data available (6 female, 6 monozygotic). We calculated a risk score for each twin and co‐twin, based on the following factors: depressive symptoms (measured with the Center for Epidemiological Studies – Depression, CES‐D), body mass index (BMI), physical activity (MET hours), life satisfaction, neuroticism, and years of education. Within each twin pair, co‐twins were assigned as having greater versus lower risk score. We ran a paired t‐test to compare EM performance (total number of recalled words in three trials of 10‐word list) in co‐twins with greater versus lower risk score. Associations of individual factors with EM were studied with exact McNemar test.ResultMean difference in EM within twin pairs was 3.38 (SD = 2.50). Pairwise correlation of EM was r = 0.75 and seven twin pairs were discordant for EM. Co‐twins with lower risk score remembered more words (M = 13.25, SD = 5.59) than their co‐twins with greater risk score (M = 12.88, SD = 5.82), but this difference was not significant (p = 0.82). Examining each risk factor individually, the strongest – non‐significant – association was that co‐twins with greater life satisfaction had better EM in 5/6 pairs (p = 0.10).ConclusionPreliminary data did not indicate any significant within‐twin pair associations of dementia risk and episodic memory. As expected, co‐twins were highly similar in EM. Ongoing data collection will result in more twin pairs and greater statistical power to see if the suggestive association of greater life satisfaction (or other factors) with better EM is evident in nonagenarians.

Self-reported sleep bruxism in 1990 and 2011 in a nationwide twin cohort: Evidence of trait persistence and genetic liability.

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. 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. 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. 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. 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.

Differences in DNA Methylation-Based Age Prediction Within Twin Pairs Discordant for Cancer.

DNA methylation-based age acceleration (DNAmAA) is associated with cancer, with both cancer tissue and blood showing increased DNAmAA. We aimed to investigate whether DNAmAA is associated with cancer risk within twin pairs discordant for cancer, and whether DNAmAA has the potential to serve as a biomarker for such. The study included 47 monozygotic and 48 same-sex-dizygotic cancer-discordant twin pairs from the Finnish Twin Cohort study with blood samples available between 17 and 31 years after the cancer diagnosis. We studied all cancers (95 pairs), then separately breast cancer (24 pairs) and all sites other than breast cancer (71 pairs). DNAmAA was calculated for seven models: Horvath, Horvath intrinsic epigenetic age acceleration, Hannum, Hannum intrinsic epigenetic age acceleration, Hannum extrinsic epigenetic age acceleration, PhenoAge and GrimAge. Within-pair differences in DNAmAA were analyzed by paired t tests and linear regression. Twin pairs sampled before cancer diagnosis did not differ significantly in DNAmAA. However, the within-pair differences in DNAmAA before cancer diagnosis increased significantly the closer the cancer diagnosis was, and this acceleration extended for years after the diagnosis. Pairs sampled after the diagnosis differed for DNAmAA with the Horvath models capturing cancer diagnosis-associated DNAmAA across all three cancer groupings. The results suggest that DNAmAA in blood is associated with cancer diagnosis. This may be due to epigenetic alterations in relation to cancer, its treatment or associated lifestyle changes. Based on the current study, the biomarker potential of DNAmAA in blood appears to be limited.

Modeling dependency structures in 450k DNA methylation data.

MotivationDNA methylation has been shown to be spatially dependent across chromosomes. Previous studies have focused on the influence of genomic context on the dependency structure, while not considering differences in dependency structure between individuals.ResultsWe modeled spatial dependency with a flexible framework to quantify the dependency structure, focusing on inter-individual differences by exploring the association between dependency parameters and technical and biological variables. The model was applied to a subset of the Finnish Twin Cohort study (N = 1611 individuals). The estimates of the dependency parameters varied considerably across individuals, but were generally consistent across chromosomes within individuals. The variation in dependency parameters was associated with bisulfite conversion plate, zygosity, sex and age. The age differences presumably reflect accumulated environmental exposures and/or accumulated small methylation differences caused by stochastic mitotic events, establishing recognizable, individual patterns more strongly seen in older individuals. Availability and implementationThe twin dataset used in the current study are located in the Biobank of the National Institute for Health and Welfare, Finland. All the biobanked data are publicly available for use by qualified researchers following a standardized application procedure (https://thl.fi/en/web/thl-biobank/for-researchers). A R-script for fitting the dependency structure to publicly available DNA methylation data with the software used in this article is provided in supplementary data.Supplementary information Supplementary data are available at Bioinformatics online.

Episodic memory and cortical amyloid pathology: PET study in cognitively discordant twin pairs

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.

Middle-age dementia risk scores and old-age cognition: a quasi-experimental population-based twin study with over 20-year follow-up.

BackgroundMiddle-age risk scores predict cognitive impairment, but it is not known if these associations are evident when controlling for shared genetic and environmental factors. Using two risk scores, self-report educational-occupational score and Cardiovascular Risk Factors, Aging and Dementia (CAIDE), we investigated if twins with higher middle-age dementia risk have poorer old-age cognition compared with their co-twins with lower risk.MethodsWe used a population-based older Finnish Twin Cohort study with middle-age questionnaire data (n=15 169, mean age=52.0 years, SD=11.8) and old-age cognition measured via telephone interview (mean age=74.1, SD=4.1, n=4302). Between-family and within-family linear regression analyses were performed.ResultsIn between-family analyses (N=2359), higher educational-occupational score was related to better cognition (B=0.76, 95% CI 0.69 to 0.83) and higher CAIDE score was associated with poorer cognition (B=−0.73, 95% CI −0.82 to -0.65). Within twin-pair differences in educational-occupational score were significantly related to within twin-pair differences in cognition in dizygotic (DZ) pairs (B=0.78, 95% CI 0.25 to 1.31; N=338) but not in monozygotic (MZ) pairs (B=0.12, 95% CI −0.44 to 0.68; N=221). Within twin-pair differences in CAIDE score were not related to within twin-pair differences in cognition: DZ B=−0.38 (95% CI −0.90 to 0.14, N=343) and MZ B=−0.05 (95% CI −0.59 to 0.49; N=226).ConclusionMiddle-age dementia risk scores predicted old-age cognition, but within twin-pair analyses gave little support for associations independent of shared environmental and genetic factors. Understanding genetic underpinnings of risk score−cognition associations is important for early detection of dementia and designing intervention trials.

An integrative machine learning approach to discovering multi-level molecular mechanisms of obesity using data from monozygotic twin pairs.

We combined clinical, cytokine, genomic, methylation and dietary data from 43 young adult monozygotic twin pairs (aged 22–36 years, 53% female), where 25 of the twin pairs were substantially weight discordant (delta body mass index > 3 kg m−2). These measurements were originally taken as part of the TwinFat study, a substudy of The Finnish Twin Cohort study. These five large multivariate datasets (comprising 42, 71, 1587, 1605 and 63 variables, respectively) were jointly analysed using an integrative machine learning method called group factor analysis (GFA) to offer new hypotheses into the multi-molecular-level interactions associated with the development of obesity. New potential links between cytokines and weight gain are identified, as well as associations between dietary, inflammatory and epigenetic factors. This encouraging case study aims to enthuse the research community to boldly attempt new machine learning approaches which have the potential to yield novel and unintuitive hypotheses. The source code of the GFA method is publically available as the R package GFA.

Life events as predictors for disability pension due to musculoskeletal diagnoses: a cohort study of Finnish twins

PurposeMusculoskeletal diagnoses (MSD) are one of the largest diagnostic groups for disability pensions (DP). This study investigated the associations between life events and DP due to MSD, considering sociodemographic, health, and familial factors.MethodsThe study sample included 18,530 Finnish twins, 24–64 years old at baseline, who responded to a questionnaire in 1981 including a 21-item life event inventory. Information on DP with diagnosis codes (ICD codes: M00–M99) were obtained from the official national pension registers. Life events were divided into family- and work-related events. “Positive change in life” was analyzed separately. Cox proportional hazards models were used to calculate hazard ratios (HR) with 95% confidence intervals (CI).ResultsDuring the follow-up of 23 years, 1273 (7%) individuals were granted DP due to MSD. In discordant pair analysis, family-related events (≥ 4 events) increased (HR 1.63, 95% CI 1.31, 2.03) and the absence of such events decreased (HR 0.68, 95% CI 0.48, 0.95) the risk of DP due to MSD. For work-related events (≥ 3 events), the risk estimates were non-significant when controlling for familial factors. Having had a positive change in life decreased the risk of DP due to MSD (HR 0.79, 95% CI 0.65, 0.96) while controlling for familial confounding, but were non-significant in the full model controlling for various covariates (HR 0.91, 95% CI 0.75, 1.12).ConclusionsThe associations between life events and the risk of DP due to MSD are complex and potentially affected by familial and other confounding factors including sociodemographics and health.

Is diversity of leisure-time sport activities associated with low back and neck-shoulder region pain? A Finnish twin cohort study.

This study investigates cross-sectional and longitudinal associations between the diversity of leisure-time sport activities and the frequencies of low back pain (LBP) and neck-shoulder region pain (NSP) in twins, including a cross-sectional within-pair design to adjust for potential familial confounding.Finnish twins born in 1975–79 (FinnTwin16 study) reported participation in leisure-time sport activities at the mean ages of 17 (1992–96) (n = 5096, 54% females) and 34 years (2010−12) (n = 3731, 57% females). Diversity assessed as the number of sport activities was categorized as 1, 2, 3, 4, and ≥ 5, excluding inactive individuals. The frequencies of LBP (n = 3201) and NSP (n = 3207), reported at age 34, were categorized as never/seldom, monthly, or weekly pain. Cross-sectional and longitudinal individual-based associations between the number of sport activities and the frequency of LBP and NSP were investigated with multinomial logistic regression analyses, adjusting for multiple confounders. Cross-sectionally, participation in ≥5 sport activities, compared to 1 sport, was associated with significantly less weekly LBP (OR = 0.63, 95%CI = 0.43–0.90), but not with NSP. Longitudinally, participation in several sport activities in adolescence had no significant association with LBP or NSP in adulthood. Cross-sectional within-pair analyses were conducted among twin pairs discordant for LBP (n = 507) and NSP (n = 579). The associations between monozygotic and dizygotic twin pairs were similar in LBP-discordant pairs but differed within NSP-discordant pairs.Participation in ≥5 sport activities in adulthood may be associated with less weekly LBP, but not with monthly LBP or the frequency of NSP. However, within-pair analyses for NSP suggest confounding due to shared familial factors.

Early adolescent aggression predicts antisocial personality disorder in young adults: a population-based study

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 3228: Tobacco smoking and circulating immune-related biomarkers in monozygotic twins

Abstract Background: Tobacco smoking is a cause of a variety of cancers by various mechanisms. Paradoxically, smoking also increases the risk of atopy and asthma, which are inversely associated with some cancers such as glioma, colorectal cancer and non-Hodgkin lymphoma, but positively associated with others such as lung cancer. Tobacco smoking may affect the immune system, which may explain some of these associations. We assessed the association between smoking and levels of 27 serum immune/inflammatory markers and DNA methylation in healthy monozygotic (MZ) twins. Methods: 67 MZ twin pairs were identified from the Finnish Twin Cohort Study. Cotinine and immune related biomarkers were measured from fasting serum samples using LC-MS/MS and Luminex multiples assays. Current smoking status was defined by cotinine &amp;gt;3.08 ng/mL. Current smokers were further categorized into low vs high smoking level by the median cotinine (78.17 ng/mL) among smokers. Questionnaire reports of current and former smoking included duration, amount (cigarettes per day [CPD]) and years since quitting. Linear mixed models were used to assess the association between smoking variables and each individual biomarker. For each smoking variable P values were adjusted for multiple comparisons using Pact, taking into account correlations among biomarkers. For biomarkers significantly associated with smoking, we assessed whether blood DNA methylation of biomarker-related genes mediated the smoking-biomarker association. Results: The median age of the study population was 24.8 years (range 21.0-68.9 years) and 56.7% were female twins. 32.1% of the twins were current smokers according to cotinine levels. Current smoking, defined by either cotinine or self-reports, was significantly associated with CCL17, B-cell activating factor (BAFF) and haptoglobin (Hp) levels respectively, after adjusting for multiple comparisons. For instance, serum cotinine was associated with increasing CCL17 levels (Pact for trend test = 0.002): the geometric mean CCL17, adjusted for age and sex among current high-level smokers was approximately 8.2% higher than noncurrent smokers. Similar positive dose-response relationships were observed for self-reported smoking variables with the 3 biomarkers. However, we found no associations between former smoking and any of the 27 biomarkers. We also found that smoking-associated DNA methylation alterations in 3 CpG sites of BAFF affected circulating CCL17 (CpG site: cg11726530) and Hp (cg09158314 and cg21784254) levels, respectively. Conclusion: Current but not former smoking may be associated with alterations in circulating levels of CCL17, BAFF and Hp, suggesting that smoking may promote B-cell activation and affect Th2 immune response, which may play a role in carcinogenesis. Further, preliminary mediation analysis suggests that smoking-induced alterations in these biomarkers may partially mediate through DNA methylation. Citation Format: Jun Wang, David Conti, Marta Epeldegui, Miina Ollikainen, Amie E. Hwang, Ann S. Hamilton, Larry Magpantay, Rachel Tyndale, Thomas M. Mack, Otoniel Martinez-Maza, Jaakko Kaprio, Wendy Cozen. Tobacco smoking and circulating immune-related biomarkers in monozygotic twins [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3228.

Sleep disruption, chronotype, shift work, and prostate cancer risk and mortality: a 30-year prospective cohort study of Finnish twins.

Sleep disruption and shift work have been associated with cancer risk, but epidemiologic evidence for prostate cancer remains limited. We aimed to prospectively investigate the association between midlife sleep- and circadian-related parameters and later prostate cancer risk and mortality in a population-based cohort of Finnish twins. Data were drawn from the Older Finnish Twin Cohort and included 11,370 twins followed from 1981 to 2012. Over the study period, 602 incident cases of prostate cancer and 110 deaths from prostate cancer occurred. Cox regression was used to evaluate associations between midlife sleep duration, sleep quality, chronotype, and shift work with prostate cancer risk and prostate cancer-specific mortality. Within-pair co-twin analyses were employed to account for potential familial confounding. Compared to "definite morning" types, "somewhat evening" types had a significantly increased risk of prostate cancer (HR 1.3; 95% CI 1.1, 1.6). Chronotype significantly modified the relationship between shift work and prostate cancer risk (p-interaction <0.001). We found no significant association between sleep duration, sleep quality, or shift work and prostate cancer risk in the overall analyses and no significant association between any sleep- or circadian-related parameter and risk in co-twin analyses. Neither sleep- nor circadian-related parameters were significantly associated with prostate cancer-specific mortality. The association between sleep disruption, chronotype, and shift work with prostate cancer risk and mortality has never before been studied in a prospective study of male twins. Our findings suggest that chronotype may be associated with prostate cancer risk and modify the association between shift work and prostate cancer risk. Future studies of circadian disruption and prostate cancer should account for this individual-level characteristic.

COGNITIVE RESERVE AS INDEXED BY EDUCATIONAL AND OCCUPATIONAL ATTAINMENT MODERATES THE ASSOCIATION BETWEEN CARDIOVASCULAR DISEASE AND DEMENTIA

Cognitive reserve (CR) hypothesis suggests that those with higher levels of reserve can tolerate risk factors of dementia better than those with lower levels of reserve. We tested if higher CR, as indexed by higher educational and occupational attainments, helps to withstand deteriorative effects of cardiovascular disease on cognition. We studied CR, history of cardiovascular disease (CVD) and old age cognition in a sample of 2284 individuals from a population-based Finnish Twin Cohort study. Summary score of middle age CR was based on five questions on educational and occupational status at a mean age of 47 years. Old age cognitive status at a mean age of 74 years was determined with two validated instruments: a self-report interview for cognitive status (TELE) and the Telephone Interview for Cognitive Status (TICS). We used Finnish dementia cutoff scores of <16 and <22.5 for TELE and TICS, respectively. CVD was obtained from hospital discharge registry data. Both CR and CVD were significant predictors of dementia after a mean follow-up of 28 years. There was also a significant CR-CVD interaction indicating that CVD was more strongly associated with dementia in those with low CR compared to those with high CR. In individuals with high CR, 2.6% (TELE) / 1.3% (TICS) of those without CVD and 0% (TELE) / 0% (TICS) of those with CVD were demented. In individuals with low CR, 30.6% (TELE) / 25% (TICS) of those without CVD and 40.5% (TELE) / 37.1% (TICS) of those with CVD were demented. Moreover, the level of CR was more strongly (B = 1.24 [95%CI 1.03; 1.44]) associated with total TELE/TICS score in those with a history of CVD compared to those without a history of CVD (B= 1.00 [95%CI 0.89; 1.11]). Our results support the CR hypothesis whereby those with higher levels of reserve tolerate risk factors of dementia better than those with low levels of reserve. Our results also demonstrate that there may be subgroups who are at elevated risk for dementia due to cardiovascular disease. Detecting high risk subgroups is important for early detection of cognitive impairment and dementia.

Alcohol intake, drinking patterns, and prostate cancer risk and mortality: a 30-year prospective cohort study of Finnish twins.

Alcohol intake may be associated with cancer risk, but epidemiologic evidence for prostate cancer is inconsistent. We aimed to prospectively investigate the association between midlife alcohol intake and drinking patterns with future prostate cancer risk and mortality in a population-based cohort of Finnish twins. Data were drawn from the Older Finnish Twin Cohort and included 11,372 twins followed from 1981 to 2012. Alcohol consumption was assessed by questionnaires administered at two time points over follow-up. Over the study period, 601 incident cases of prostate cancer and 110 deaths from prostate cancer occurred. Cox regression was used to evaluate associations between weekly alcohol intake and binge drinking patterns with prostate cancer risk and prostate cancer-specific mortality. Within-pair co-twin analyses were performed to control for potential confounding by shared genetic and early environmental factors. Compared to light drinkers (≤3 drinks/week; non-abstainers), heavy drinkers (>14 drinks/week) were at a 1.46-fold higher risk (HR 1.46; 95% CI 1.12, 1.91) of prostate cancer, adjusting for important confounders. Among current drinkers, binge drinkers were at a significantly increased risk of prostate cancer (HR 1.28; 95% CI 1.06, 1.55) compared to non-binge drinkers. Abstainers were at a 1.90-fold higher risk (HR 1.90; 95% CI 1.04, 3.47) of prostate cancer-specific mortality compared to light drinkers, but no other significant associations for mortality were found. Co-twin analyses suggested that alcohol consumption may be associated with prostate cancer risk independent of early environmental and genetic factors. Heavy regular alcohol consumption and binge drinking patterns may be associated with increased prostate cancer risk, while abstinence may be associated with increased risk of prostate cancer-specific mortality compared to light alcohol consumption.