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Objectives Genetic predisposition and maternal body mass index (BMI) are risk factors for childhood adiposity, defined by either BMI or overweight. We aimed to investigate whether childhood-specific genetic risk scores (GRSs) for adiposity-related traits are associated with childhood adiposity independent of maternal BMI, or whether the associations are modified by maternal BMI. Methods We constructed a weighted 26-SNP child BMI-GRS and a weighted 17-SNP child obesity-GRS in overall 1674 genotyped children within the Danish National Birth Cohort. We applied a case-cohort (N = 1261) and exposure-based cohort (N = 912) sampling design. Using logistic regression models we estimated associations of the GRSs and child overweight at age 7 years and examined if the GRSs influence child adiposity independent of maternal BMI (per standard deviation units). Results In the case-cohort design analysis, maternal BMI and the child GRSs were associated with increased odds for childhood overweight [OR for maternal BMI: 2.01 (95% CI: 1.86; 2.17), OR for child BMI-GRS: 1.56 (95% CI: 1.47; 1.66), and OR for child obesity-GRS 1.46 (95% CI: 1.37; 1.54)]. Adjustment for maternal BMI did not change the results, and there were no significant interactions between the GRSs and maternal BMI. However, in the exposure-based cohort design analysis, significant interactions between the child GRSs and maternal BMI on child overweight were observed, suggesting 0.85–0.87-fold attenuation on ORs of child overweight at higher values of maternal BMI and child GRS. Conclusion GRSs for childhood adiposity are strongly associated with childhood adiposity even when adjusted for maternal BMI, suggesting that the child-specific GRSs and maternal BMI contribute to childhood overweight independent of each other. However, high maternal BMI may attenuate the effects of child GRSs in children.

Contains fulltext : 237012.pdf (Publisher’s version ) (Closed access) Background: Investigating siblings of probands with affective disorders enables the identification of psychopathology-related risk features. Leveraging data from an older adult sample, as compared to most previous sibling studies, enabled us to study more definitive clinical profiling across the lifespan. We examined prevalence of depressive/anxiety disorders in siblings, proband-sibling resemblance in psychopathology-related features, and whether unaffected siblings showed higher levels of these features than healthy controls. Methods: The sample (N=929; Mage=50.6) consisted of 256 probands with lifetime depressive and/or anxiety disorders, their 380 siblings, and 293 healthy controls without affected relatives. Fifteen psychopathology-related features were investigated across four domains: mental health symptoms, social vulnerabilities, cognitive vulnerabilities, and personality. Results: Lifetime disorders were present in 50.3% of siblings. Prevalence was 2-3 times higher than Dutch population frequencies. We found small to medium probandsibling resemblance across psychopathology-related features (ρ=0.10-0.32). Unaffected siblings reported poorer interpersonal functioning and more negative life events, childhood trauma, and rumination than healthy controls. Limitations Due to the cross-sectional study design, the directionality of effects cannot be determined. No inferences can be made about potential differences in familial resemblance in psychopathology-related features between high- and low-risk families. Conclusions: Siblings of probands with affective disorders are at higher risk for depressive/anxiety disorders. Even when unaffected, still show higher psychosocial vulnerability than healthy controls. Nevertheless, the only modest proband-sibling resemblance across psychopathology-related features suggests that individual mechanisms differentiate clinical trajectories across the lifespan. Identification of these mechanisms is crucial to improve resilience in subjects with familial risk. 10 p.

Background Obesity susceptibility genes are highly expressed in the brain suggesting that they might exert their influence on body weight through eating-related behaviors. Objectives To examine whether the genetic susceptibility to obesity is mediated by eating behavior patterns. Methods Participants were 3977 twins (33% monozygotic, 56% females), aged 31–37 y, from wave 5 of the FinnTwin16 study. They self-reported their height and weight, eating behaviors (15 items), diet quality, and self-measured their waist circumference (WC). For 1055 twins with genome-wide data, we constructed a polygenic risk score for BMI (PRSBMI) using almost 1 million single nucleotide polymorphisms. We used principal component analyses to identify eating behavior patterns, twin modeling to decompose correlations into genetic and environmental components, and structural equation modeling to test mediation models between the PRSBMI, eating behavior patterns, and obesity measures. Results We identified 4 moderately heritable (h2 = 36–48%) eating behavior patterns labeled “snacking,” “infrequent and unhealthy eating,” “avoidant eating,” and “emotional and external eating.” The highest phenotypic correlation with obesity measures was found for the snacking behavior pattern (r = 0.35 for BMI and r = 0.32 for WC; P < 0.001 for both), largely due to genetic factors in common (bivariate h2 > 70%). The snacking behavior pattern partially mediated the association between the PRSBMI and obesity measures (βindirect = 0.06; 95% CI: 0.02, 0.09; P = 0.002 for BMI; and βindirect = 0.05; 95% CI: 0.02, 0.08; P = 0.003 for WC). Conclusions Eating behavior patterns share a common genetic liability with obesity measures and are moderately heritable. Genetic susceptibility to obesity can be partly mediated by an eating pattern characterized by frequent snacking. Obesity prevention efforts might therefore benefit from focusing on eating behavior change, particularly in genetically susceptible individuals.

Objective:To more precisely and comprehensively estimate the genetic and environmental correlations between various indices of obesity and BP.Methods:We estimated heritability and genetic correlations of obesity indices with BP in the Oman family study (n=1231). Ambulatory and office beat-to-beat BP was measured and mean values for SBP and DBP during daytime, sleep, 24-h and 10min at rest were calculated. Different indices were used to quantify obesity and fat distribution: BMI, percentage of body fat (%BF), waist circumference and waist-to-height ratio (WHtR). SOLAR software was used to perform univariate and bivariate quantitative genetic analyses adjusting for age, age2, sex, age-sex and age2- sex interactions.Results:Heritabilities of BP ranged from 30.2 to 38.2% for ambulatory daytime, 16.8 - 21.4% for sleeping time, 32.1 - 40.4% for 24-h and 22 - 24.4% for office beat-to-beat measurements. Heritabilities for obesity indices were 67.8% for BMI, 52.2% for %BF, 37.3% for waist circumference and 37.9% for WHtR. All obesity measures had consistently positive phenotypic correlations with ambulatory and office beat-to-beat SBP and DBP (r-range: 0.14 - 0.32). Genetic correlations of obesity indices with SBP and DBP were higher than environmental correlations (rG: 0.16 - 0.50; rE: 0.01 - 0.31).Conclusion:The considerable genetic overlap between a variety of obesity indices and both ambulatory and office beat-to-beat BP highlights the relevance of pleiotropic genes. Future GWAS analyses should discover the specific genes both influencing obesity indices and BP to help unravel their shared genetic background.

BACKGROUND AND AIMS: Research on adolescent predictors of later alcohol misuse is typically conducted on samples of singletons, and associations may be confounded by between-family differences. To address potential confounding, we applied a co-twin comparison design to evaluate whether differences between co-twins in a wide array of adolescent risk factors predicted differences in young adult alcohol misuse. DESIGN: Longitudinal study in which associations between characteristics of the sample as adolescents were used to predict young adult alcohol misuse in individual-level analyses and co-twin comparisons. SETTING: Finland. PARTICIPANTS: A total of 3402 individuals (1435 complete twin pairs; 36% monozygotic; 57% female) from the FinnTwin12 study. MEASUREMENTS: The young adult alcohol misuse outcome was a composite score of alcohol use and intoxication frequency. Adolescent predictors included factor scores representing academic performance, substance use, externalizing problems, internalizing problems, peer environment, physical health and relationship with parents; and single measures tapping alcohol expectancies, life events and pubertal development. FINDINGS: In individual-level analyses, individuals with higher adolescent substance use, externalizing problems, time with friends, peer deviance, sports involvement, sleeping difficulties, parental discipline, positive alcohol expectancies and difficulty of life events reported higher alcohol misuse in young adulthood (Ps < 0.019, R(2) = 0.0003–0.0310%). Conversely, those with higher adolescent internalizing problems, parent–child relationship quality and time with parents reported lower alcohol misuse (Ps < 0021, R(2) = 0.0018–0.0093%). The associations with adolescent substance use and alcohol expectancies remained significant in co-twin comparisons (Ps < 0.049, R(2) = 0.0019–0.0314%). Further, academic performance emerged as a significant predictor, such that individuals with higher grades compared with their co-twin reported higher young adult alcohol misuse (Ps < 0.029, R(2) = 0.0449–0.0533%). CONCLUSIONS: Adolescent substance use, positive alcohol expectancies and higher academic performance appear to be robust predictors of later alcohol misuse.

From the literature it is not clear whether low resting heart rate (HR) reflects low or high sensitivity to the detrimental effects of adverse environments on externalizing problems. We studied parental psychiatric history (PH), reflecting general vulnerability, as possible moderator explaining these inconsistencies. Using Linear Mixed Models, we analyzed data from 1914 subjects, obtained in three measurement waves (mean age 11, 13.5, and 16 years) from the TRacking Adolescents’ Individual Lives Survey population-based cohort and the parallel clinic-referred cohort. As hypothesized, more chronic stressors predicted more externalizing problems in vulnerable individuals with high resting HR but not in those with low resting HR, suggesting high vs. low sensitivity, respectively, to adverse environmental influences. Low sensitivity to adverse environmental influences in vulnerable individuals exposed to high stressor levels was additionally confirmed by high heart rate variability (Root Mean Squared Successive Difference; RMSSD). In adolescents with low vulnerability, in contrast, the association between chronic stressors and externalizing problems did not substantially differ by resting HR and RMSSD. Future research may demonstrate whether our findings extend to other adverse, or beneficial, influences. Notwithstanding their theoretical interest, the effects were small, only pertained to parent-reported externalizing problems, refer to a small subset of respondents in our sample, and are in need of replication. We conclude that HR and RMSSD are unlikely to be strong moderators of the association between stressors and externalizing problems.

BACKGROUND: Inter-individual variance in skeletal muscle is closely related to genetic architecture and epigenetic regulation. Studies have examined genetic and epigenetic relationships with characteristics of ageing muscle separately, while no study has combined both genetic and epigenetic profiles in ageing muscle research. The aim of this study was to evaluate the association between combined genetic and methylation scores and skeletal muscle phenotypes in older women. METHODS: Forty-eight older Caucasian women (aged 65-79 years) were included in this study. Biceps brachii thickness and vastus lateralis anatomical cross-sectional area (ACSAVL ) were measured by ultrasonography. Maximum isometric elbow flexion (MVCEF ) and knee extension (MVCKE ) torques were measured by a customized dynamometer. The muscle-driven genetic predisposition score (GPSSNP ) was calculated based on seven muscle-related single nucleotide polymorphisms (SNPs). DNA methylation levels of whole blood samples were analysed using Infinium MethylationEPIC BeadChip arrays. The DNA methylation score was calculated as a weighted sum of methylation levels of sarcopenia-driven CpG sites (MSSAR ) or an overall gene-wise methylation score (MSSNP , the mean methylation level of CpG sites located in muscle-related genes). Linear regression models were built to study genetic and epigenetic associations with muscle size and strength. Three models were built with both genetic and methylation scores: (1) MSSAR + GPSSNP , (2) MSSNP + GPSSNP , and (3) gene-wise combined scores which were calculated as the ratio of the SNP score to the mean methylation level of promoters in the corresponding gene. Additional models with only a genetic or methylation score were also built. All models were adjusted for age and BMI. RESULTS: MSSAR was negatively associated with ACSAVL , MVCEF , and MVCKE and explained 10.1%, 35.5%, and 40.1% of the variance, respectively. MSSAR explained more variance in these muscular phenotypes than GPSSNP , MSSNP , and models including both genetic and methylation scores. MSSNP and GPSSNP accounted for less than 8% and 5% of the variance in all muscular phenotypes, respectively. The genotype and methylation level of CNTF was positively related to MVCKE (P = 0.03) and explained 12.2% of the variance. The adjusted R2 and Akaike information criterion showed that models with only a MSSAR performed the best in explaining inter-individual variance in muscular phenotypes. CONCLUSIONS: Our results improve the understanding of inter-individual variance in muscular characteristics of older women and suggest a possible application of a sarcopenia-driven methylation score to muscle strength estimation in older women while the combination with a genetic score still needs to be further studied. ispartof: JOURNAL OF CACHEXIA SARCOPENIA AND MUSCLE vol:11 issue:6 pages:1548-1561 ispartof: location:Germany status: published

Background Earlier pubertal timing has been observed in many countries. We aimed to explore if prenatal exposure to maternal obesity, smoking, and alcohol intake was associated with timing of puberty by use of a novel marker of pubertal timing: ‘the height difference in standard deviations’ (HD:SDS). Methods HD:SDS is the difference between pubertal height in standard deviations and adult height in standard deviations, and it correlates well with age at peak height velocity. Pubertal height was measured by health care professionals at approximately 13 years in boys and 11 years in girls, and the children’s adult height was predicted from parental height reported by the mothers during pregnancy. Information on HD:SDS was available for 42,849 of 56,641 eligible boys and girls from the Danish National Birth Cohort born 2000–2003. In a subsample, HD:SDS was validated against age at the following self-reported pubertal milestones: Tanner stages, menarche, first ejaculation, voice break, acne, and axillary hair. Prenatal exposures were reported by mothers during pregnancy. Results HD:SDS correlated moderately with the pubertal milestones considered (correlation coefficients: − 0.20 to − 0.53). With normal weight (body mass index (BMI): 18.5–24.9 kg/m2) as the reference, maternal pre-pregnancy obesity (BMI: 30.0+ kg/m2) was associated with earlier pubertal timing: 0.23 (95% confidence interval (CI): 0.18, 0.28) higher HD:SDS in boys and 0.19 (95% CI, 0.14, 0.24) higher HD:SDS in girls. Maternal smoking was not associated with pubertal timing. Compared to alcohol abstainers, maternal intake of > 3 units of alcohol weekly was associated with later puberty in boys only: 0.14 (95% CI, 0.05, 0.24) lower HD:SDS. Conclusion As correlations between HD:SDS and the considered pubertal milestones were comparable to those reported in the literature between age a peak height velocity and the considered pubertal milestones, the validity of HD:SDS seems acceptable. Maternal pre-pregnancy obesity was associated with earlier pubertal timing in both sexes, and maternal alcohol intake during pregnancy was associated with later pubertal timing in boys. Maternal smoking has been linked to earlier timing of puberty, but this was not replicated in our setting using HD:SDS as a marker of pubertal timing.

We aimed to detect Attention-deficit/hyperactivity (ADHD) risk-conferring genes in adults. In children, ADHD is characterized by age-inappropriate levels of inattention and/or hyperactivity-impulsivity and may persists into adulthood. Childhood and adulthood ADHD are heritable, and are thought to represent the clinical extreme of a continuous distribution of ADHD symptoms in the general population. We aimed to leverage the power of studies of quantitative ADHD symptoms in adults who were genotyped. Within the SAGA (Study of ADHD trait genetics in adults) consortium, we estimated the single nucleotide polymorphism (SNP)-based heritability of quantitative self-reported ADHD symptoms and carried out a genome-wide association meta-analysis in nine adult population-based and case-only cohorts of adults. A total of n = 14,689 individuals were included. In two of the SAGA cohorts we found a significant SNP-based heritability for self-rated ADHD symptom scores of respectively 15% (n = 3656) and 30% (n = 1841). The top hit of the genome-wide meta-analysis (SNP rs12661753; p-value = 3.02 × 10 −7 ) was present in the long non-coding RNA gene STXBP5-AS1. This association was also observed in a meta-analysis of childhood ADHD symptom scores in eight population-based pediatric cohorts from the Early Genetics and Lifecourse Epidemiology (EAGLE) ADHD consortium (n = 14,776). Genome-wide meta-analysis of the SAGA and EAGLE data (n = 29,465) increased the strength of the association with the SNP rs12661753. In human HEK293 cells, expression of STXBP5-AS1 enhanced the expression of a reporter construct of STXBP5, a gene known to be involved in “SNAP” (Soluble NSF attachment protein) Receptor” (SNARE) complex formation. In mouse strains featuring different levels of impulsivity, transcript levels in the prefrontal cortex of the mouse ortholog Gm28905 strongly correlated negatively with motor impulsivity as measured in the five choice serial reaction time task (r 2 = − 0.61; p = 0.004). Our results are consistent with an effect of the STXBP5-AS1 gene on ADHD symptom scores distribution and point to a possible biological mechanism, other than antisense RNA inhibition, involved in ADHD-related impulsivity levels.

Loos, Ruth J F/0000-0002-8532-5087; Kaprio, Jaakko/0000-0002-3716-2455; Huibregtse, Brooke M./0000-0003-0977-7249; de Freitas, Duarte Luis/0000-0001-6642-3370; Aliev, Fazil/0000-0001-8357-4699; Medda, Emanuela/0000-0003-4837-4549; Bartels, Meike/0000-0002-9667-7555; Latvala, Antti/0000-0001-5695-117X; Sund, Reijo/0000-0002-6268-8117; Rebato, Esther/0000-0003-1221-8501; Silventoinen, Karri/0000-0003-1759-3079; Aaltonen, Sari/0000-0002-2873-4263; Nistico, Lorenza/0000-0003-1805-6240; Knafo-Noam, Ariel/0000-0003-0613-1960; van Beijsterveldt, Toos/0000-0002-6617-4201; Harden, Kathryn/0000-0002-1557-6737; Willemsen, Gonneke/0000-0003-3755-0236; Pahlen, Shandell/0000-0003-0753-4155 WOS: 000465255700021 PubMed: 30950584 Objective The objective of this study was to analyze how parental education modifies the genetic and environmental variances of BMI from infancy to old age in three geographic-cultural regions. Methods A pooled sample of 29 cohorts including 143,499 twin individuals with information on parental education and BMI from age 1 to 79 years (299,201 BMI measures) was analyzed by genetic twin modeling. Results Until 4 years of age, parental education was not consistently associated with BMI. Thereafter, higher parental education level was associated with lower BMI in males and females. Total and additive genetic variances of BMI were smaller in the offspring of highly educated parents than in those whose parents had low education levels. Especially in North American and Australian children, environmental factors shared by co-twins also contributed to the higher BMI variation in the low education level category. In Europe and East Asia, the associations of parental education with mean BMI and BMI variance were weaker than in North America and Australia. Conclusions Lower parental education level is associated with higher mean BMI and larger genetic variance of BMI after early childhood, especially in the obesogenic macro-environment. The interplay among genetic predisposition, childhood social environment, and macro-social context is important for socioeconomic differences in BMI. Collaborative Project of Development of Anthropometrical Measures in Twins (Academy of Finland) [266592]; Swedish Research Council through the Swedish Initiative for Research on Microdata in the Social and Medical Sciences Framework Grant [340-2013-5867]; Stockholm County Council (ALF projects)Stockholm County Council; Swedish Heart-Lung FoundationSwedish Heart-Lung Foundation; Swedish Asthma and Allergy Association's Research Foundation; Netherlands Organization for Scientific ResearchNetherlands Organization for Scientific Research (NWO); MagW/ZonMW [904-61-090, 985-10-002, 912-10-020, 904-61-193, 480-04-004, 463-06-001, 451-04-034, 400-05-717, Addiction-31160008, Middelgroot-911-09-032, Spinozapremie-56-464-14192]; Vrije University's Institute for Health and Care Research; European Research Council (ERC)European Research Council (ERC) [230374]; Avera Institute, Sioux Falls, South Dakota; European Network for Genetic and Genomic Epidemiology (ENGAGE) [FP7-HEALTH-F4-2007, 201413]; National Institute of Alcohol Abuse and AlcoholismUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Alcohol Abuse & Alcoholism (NIAAA) [AA-12502, AA-00145, AA-09203]; Academy of Finland Center of Excellence in Complex Disease GeneticsAcademy of Finland [213506, 129680]; Academy of FinlandAcademy of Finland [100499, 205585, 118555, 141054, 265240, 264146, 312073]; Fund of Scientific Research, FlandersFWO; Twins, a nonprofit Association for Scientific Research in Multiple Births (Belgium); Cancer Research UKCancer Research UK [C1418/A7974]; European Union's Seventh Framework Programmes ENGAGE Consortium [HEALTH-F4-2007-201413]; Biobank Standardization and Harmonization for Research Excellence in the European Union [HEALTH-F4-2010-261433]; Kirikkale UniversityKirikkale University [2009/43]; Scientific and Technological Research Council of TurkeyTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [114C117]; Osaka University's International Joint Research Promotion Program; National Institutes of Health (NIH)United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01HD068435, R01MH062375]; California Tobacco-Related Disease Research ProgramUniversity of California System [7RT-0134H, 8RT-0107H, 6RT-0354H]; NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [1R01ESO15150-01, AA023322, HD081437, R21AG039572]; National Institute on Aging (NIA)United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Aging (NIA) [1R01AG13662-01A2]; National Institute on Drug AbuseUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Drug Abuse (NIDA) [DA011015]; Longitudinal Twin Study grant [HD10333]; MSU; National Institute of Mental Health (NIMH)United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Mental Health (NIMH) [R01MH081813, R01MH0820-54, R01MH092377-02, R21MH070542-01, R03MH63851-01]; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) [R01HD066040]; MSU Foundation [11-SPG-2518]; NIMHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Mental Health (NIMH) [R01MH58354]; NIH/NIAUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Aging (NIA) [R01AG018384, R01AG018386, R01AG022381, R01AG022982]; VA San Diego Center of Excellence for Stress and Mental Health; Cooperative Studies Program of the Office of Research & Development of the US Department of Veterans Affairs (VA); Global Research Network Program of the National Research Foundation (NRF) [2011-220-E00006]; NRF of Korea [NRF-371-2011-1 B00047]; Japan Society for the Promotion of ScienceMinistry of Education, Culture, Sports, Science and Technology, Japan (MEXT)Japan Society for the Promotion of Science [15H05105]; National Health and Medical Research CouncilNational Health and Medical Research Council of Australia [1079102]; ERCEuropean Research Council (ERC) [240994]; [POCI/DES/56834/2004]; [5T32DA017637]; [5T32AG052371] This study was conducted within the Collaborative Project of Development of Anthropometrical Measures in Twins (Academy of Finland Grant 266592). Funding for individual collaborators is as follows. The Child and Adolescent Twin Study in Sweden is supported by the Swedish Research Council through the Swedish Initiative for Research on Microdata in the Social and Medical Sciences Framework Grant 340-2013-5867, grants provided by the Stockholm County Council (ALF projects), the Swedish Heart-Lung Foundation, and the Swedish Asthma and Allergy Association's Research Foundation. The Netherlands Twin Register acknowledges support from the Netherlands Organization for Scientific Research and MagW/ZonMW Grants 904-61-090, 985-10-002, 912-10-020, 904-61-193,480-04-004, 463-06-001, 451-04-034, 400-05-717, Addiction-31160008, Middelgroot-911-09-032, and Spinozapremie-56-464-14192; Vrije University's Institute for Health and Care Research; the European Research Council (ERC; grant 230374); and the Avera Institute, Sioux Falls, South Dakota. Data collection and analyses in Finnish twin cohorts have been supported by the European Network for Genetic and Genomic Epidemiology (ENGAGE; FP7-HEALTH-F4-2007, grant agreement 201413), the National Institute of Alcohol Abuse and Alcoholism (grants AA-12502, AA-00145, and AA-09203 to R. J. Rose), the Academy of Finland Center of Excellence in Complex Disease Genetics (grants 213506 and 129680), and the Academy of Finland (grants 100499, 205585, 118555, 141054, 265240, 264146, and 312073 to J. Kaprio). Since its origin, the East Flanders Prospective Survey has been partly supported by grants from the Fund of Scientific Research, Flanders and Twins, a nonprofit Association for Scientific Research in Multiple Births (Belgium). Gemini was supported by a grant from Cancer Research UK (C1418/A7974). Data collection and research stemming from the Norwegian Twin Registry are supported, in part, by the European Union's Seventh Framework Programmes ENGAGE Consortium (grant agreement HEALTH-F4-2007-201413) and Biobank Standardization and Harmonization for Research Excellence in the European Union (grant agreement HEALTH-F4-2010-261433). Madeira data come from Genetic and Environmental Influences on Physical Activity, Fitness and Health: the Madeira Family Study (project reference: POCI/DES/56834/2004, founded by the Portuguese agency for research [the Foundation for Science and Technology]). S. Y. Oncel and F. Aliev are supported by a Kirikkale University research grant (2009/43) and a Scientific and Technological Research Council of Turkey grant (114C117). K. Silventoinen is supported by Osaka University's International Joint Research Promotion Program. The Boston University Twin Project is funded by grants (R01HD068435 and R01MH062375) from the National Institutes of Health (NIH) to K. J. Saudino. The California Twin Program was supported by the California Tobacco-Related Disease Research Program (7RT-0134H, 8RT-0107H, and 6RT-0354H) and NIH (1R01ESO15150-01). The Carolina African American Twin Study of Aging was funded by a grant from the National Institute on Aging (NIA; 1R01AG13662-01A2) to K. E. Whitfield. The Colorado Twin Registry is funded by National Institute on Drug Abuse grant DA011015 and Longitudinal Twin Study grant HD10333; B. M. Huibregtse is supported by 5T32DA017637 and 5T32AG052371.; The Michigan State University (MSU) Twin Registry has been supported by MSU, as well as by grants R01MH081813, R01MH0820-54, R01MH092377-02, R21MH070542-01, and R03MH63851-01 from the National Institute of Mental Health (NIMH), grant R01HD066040 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), and grant 11-SPG-2518 from the MSU Foundation. The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of NIMH, NICHD, or NIH. The University of Southern California Twin Study is funded by a grant from NIMH (R01MH58354). The Texas Twin Project is currently funded by grants AA023322 and HD081437 from NIH. The Vietnam Era Twin Study of Aging was supported by NIH/NIA grants R01AG018384, R01AG018386, R01AG022381, and R01AG022982 and, in part, with resources of the VA San Diego Center of Excellence for Stress and Mental Health. The Cooperative Studies Program of the Office of Research & Development of the US Department of Veterans Affairs (VA) has provided financial support for the development and maintenance of the Vietnam Era Twin Registry. The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of NIA/NIH or VA. The National Academy of Sciences-National Research Council Twin Registry acknowledges financial support from NIH grant R21AG039572. The Korean TwinFamily Register was supported by the Global Research Network Program of the National Research Foundation (NRF; 2011-220-E00006). The South Korea Twin Registry is supported by the NRF of Korea (NRF-371-2011-1 B00047). The West Japan Twins and Higher Order Multiple Births Registry was supported by a Grant-inAid for Scientific Research (B) (15H05105) from the Japan Society for the Promotion of Science. This research was facilitated through access to Twins Research Australia, a national resource supported by a Centre of Research Excellence Grant (1079102) from the National Health and Medical Research Council. The Longitudinal Israeli Study of Twins was funded by Starting Grant 240994 from the ERC to A. Knafo-Noam.

Developmental dyslexia (DD) is one of the most prevalent learning disorders, with high impact on school and psychosocial development and high comorbidity with conditions like attention-deficit hyperactivity disorder (ADHD), depression, and anxiety. DD is characterized by deficits in different cognitive skills, including word reading, spelling, rapid naming, and phonology. To investigate the genetic basis of DD, we conducted a genome-wide association study (GWAS) of these skills within one of the largest studies available, including nine cohorts of reading-impaired and typically developing children of European ancestry (N = 2562–3468). We observed a genome-wide significant effect (p, Translational Psychiatry, 9 (1), ISSN:2158-3188

The older Finnish Twin Cohort (FTC) was established in 1974. The baseline survey was in 1975, with two follow-up health surveys in 1981 and 1990. The fourth wave of assessments was done in three parts, with a questionnaire study of twins born during 1945–1957 in 2011–2012, while older twins were interviewed and screened for dementia in two time periods, between 1999 and 2007 for twins born before 1938 and between 2013 and 2017 for twins born in 1938–1944. The content of these wave 4 assessments is described and some initial results are described. In addition, we have invited twin-pairs, based on response to the cohortwide surveys, to participate in detailed in-person studies; these are described briefly together with key results. We also review other projects based on the older FTC and provide information on the biobanking of biosamples and related phenotypes.

Background Amyloid pathology is the pathological hallmark in Alzheimer’s disease (AD) and can precede clinical dementia by decades. So far it remains unclear how amyloid pathology leads to cognitive impairment and dementia. To design AD prevention trials it is key to include cognitively normal subjects at high risk for amyloid pathology and to find predictors of cognitive decline in these subjects. These goals can be accomplished by targeting twins, with additional benefits to identify genetic and environmental pathways for amyloid pathology, other AD biomarkers, and cognitive decline. Methods From December 2014 to October 2017 we enrolled cognitively normal participants aged 60 years and older from the ongoing Manchester and Newcastle Age and Cognitive Performance Research Cohort and the Netherlands Twins Register. In Manchester we included single individuals, and in Amsterdam monozygotic twin pairs. At baseline, participants completed neuropsychological tests and questionnaires, and underwent physical examination, blood sampling, ultrasound of the carotid arteries, structural and resting state functional brain magnetic resonance imaging, and dynamic amyloid positron emission tomography (PET) scanning with [18F]flutemetamol. In addition, the twin cohort underwent lumbar puncture for cerebrospinal fluid collection, buccal cell collection, magnetoencephalography, optical coherence tomography, and retinal imaging. Results We included 285 participants, who were on average 74.8 ± 9.7 years old, 64% female. Fifty-eight participants (22%) had an abnormal amyloid PET scan. Conclusions A rich baseline dataset of cognitively normal elderly individuals has been established to estimate risk factors and biomarkers for amyloid pathology and future cognitive decline. Electronic supplementary material The online version of this article (10.1186/s13195-018-0406-7) contains supplementary material, which is available to authorized users.

Exposure to psychological trauma is a strong risk factor for several debilitating disorders including post-traumatic stress disorder (PTSD) and depression. Besides the impact on mental well-being and behavior in the exposed individuals, it has been suggested that psychological trauma can affect the biology of the individuals, and even have biological and behavioral consequences on the offspring of exposed individuals. While knowledge of possible epigenetic underpinnings of the association between exposure to trauma and risk of PTSD has been discussed in several reviews, it remains to be established whether trauma-induced epigenetic modifications can be passed from traumatized individuals to subsequent generations of offspring. The aim of this paper is to review the emerging literature on evidence of transgenerational inheritance due to trauma exposure on the epigenetic mechanism of DNA methylation in humans. Our review found an accumulating amount of evidence of an enduring effect of trauma exposure to be passed to offspring transgenerationally via the epigenetic inheritance mechanism of DNA methylation alterations and has the capacity to change the expression of genes and the metabolome. This manuscript summarizes and critically reviews the relevant original human studies in this area. Thus, it provides an overview of where we stand, and a clearer vision of where we should go in terms of future research directions.

Background: It is well known that metabolic risk factors of cardiovascular diseases are correlated, but the background of this clustering in children is more poorly known than in adults. Thus, we studied the contribution of genetic and environmental factors to the clustering of metabolic traits in childhood and adolescence. Data and Methods: Nine metabolic traits were measured in 214 complete twin pairs aged 3-18 years in the Autonomous Region of Madeira, Portugal, in 2007 and 2008. The variation of and covariations between the traits were decomposed into genetic and environmental components by using classical genetic twin modeling. Results: A model, including additive genetic and environmental factors unique for each twin individual, explained the variation of metabolic factors well. Under this model, the heritability estimates varied from 0.47 (systolic blood pressure in children under 12 years of age) to 0.91 (high-density lipoprotein [HDL] cholesterol in adolescents 12 years of age or older). The most systematic correlations were found between adiposity (body mass index and waist circumference) and blood lipids (HDL cholesterol, low-density lipoprotein cholesterol, and triglycerides), as well as blood pressure. These correlations were mainly explained by common genetic factors. Conclusions: Our results suggest that obesity, in particular, is behind the clustering of metabolic factors in children and adolescents. Both general and abdominal obesity partly share the same genetic background as blood lipids and blood pressure. Obesity prevention early in childhood is important in reducing the risk of metabolic diseases in adulthood.

We analyzed birth order differences in means and variances of height and body mass index (BMI) in monozygotic (MZ) and dizygotic (DZ) twins from infancy to old age. The data were derived from the international CODATwins database. The total number of height and BMI measures from 0.5 to 79.5 years of age was 397,466. As expected, first-born twins had greater birth weight than second-born twins. With respect to height, first-born twins were slightly taller than second-born twins in childhood. After adjusting the results for birth weight, the birth order differences decreased and were no longer statistically significant. First-born twins had greater BMI than the second-born twins over childhood and adolescence. After adjusting the results for birth weight, birth order was still associated with BMI until 12 years of age. No interaction effect between birth order and zygosity was found. Only limited evidence was found that birth order influenced variances of height or BMI. The results were similar among boys and girls and also in MZ and DZ twins. Overall, the differences in height and BMI between first- and second-born twins were modest even in early childhood, while adjustment for birth weight reduced the birth order differences but did not remove them for BMI.

Summary Background: Recent investigations suggest that biodiversity loss might impair the functioning and sustainability of ecosystems. Although deep-sea ecosystems are the most extensive on Earth, represent the largest reservoir of biomass, and host a large proportion of undiscovered biodiversity, the data needed to evaluate the consequences of biodiversity loss on the ocean floor are completely lacking. Results: Here, we present a global-scale study based on 116 deep-sea sites that relates benthic biodiversity to several independent indicators of ecosystem functioning and efficiency. We show that deep-sea ecosystem functioning is exponentially related to deep-sea biodiversity and that ecosystem efficiency is also exponentially linked to functional biodiversity. These results suggest that a higher biodiversity supports higher rates of ecosystem processes and an increased efficiency with which these processes are performed. The exponential relationships presented here, being consistent across a wide range of deep-sea ecosystems, suggest that mutually positive functional interactions (ecological facilitation) can be common in the largest biome of our biosphere. Conclusions: Our results suggest that a biodiversity loss in deep-sea ecosystems might be associated with exponential reductions of their functions. Because the deep sea plays a key role in ecological and biogeochemical processes at a global scale, this study provides scientific evidence that the conservation of deep-sea biodiversity is a priority for a sustainable functioning of the worlds’ oceans.

There is growing concern about elevated blood pressure (BP) in children. The evidence for familial aggregation of childhood BP is substantial. Twin studies have shown that a large part of the familial aggregation of childhood BP is due to genes. The first part of this review provides the latest progress in gene finding for childhood BP, focusing on the combined effects of multiple loci identified from the genome-wide association studies on adult BP. We further review the evidence on the contribution of the genetic components of other family risk factors to the familial aggregation of childhood BP including obesity, birth weight, sleep quality, sodium intake, parental smoking, and socioeconomic status. At the end, we emphasize the promise of using genomic-relatedness-matrix restricted maximum likelihood (GREML) analysis, a method that uses genome-wide data from unrelated individuals, in answering a number of unsolved questions in the familial aggregation of childhood BP.

Background: College or university is a critical period regarding unhealthy changes in eating behaviours in students. Therefore, the purpose of this study was to explore which factors influence Belgian (European) university students' eating behaviour, using a qualitative research design. Furthermore, we aimed to collect ideas and recommendations in order to facilitate the development of effective and tailored intervention programs aiming to improve healthy eating behaviours in university students. Methods: Using a semi-structured question guide, five focus group discussions have been conducted consisting of 14 male and 21 female university students from a variety of study disciplines, with a mean age of 20.6 +/- 1.7 yrs. Using Nvivo9, an inductive thematic approach was used for data analysis. Results: After the transition from secondary school to university, when independency increases, students are continuously challenged to make healthful food choices. Students reported to be influenced by individual factors (e. g. taste preferences, self-discipline, time and convenience), their social networks (e. g. (lack of) parental control, friends and peers), physical environment (e. g. availability and accessibility, appeal and prices of food products), and macro environment (e. g. media and advertising). Furthermore, the relationships between determinants and university students' eating behaviour seemed to be moderated by university characteristics, such as residency, student societies, university lifestyle and exams. Recommendations for university administrators and researchers include providing information and advice to enhance healthy food choices and preparation (e. g. via social media), enhancing self-discipline and self-control, developing time management skills, enhancing social support, and modifying the subjective as well as the objective campus food environment by e. g. making healthy foods price-beneficial and by providing vending machines with more healthy products. Conclusions: This is the first European study examining perceived determinants of eating behaviour in university students and collecting ideas and recommendations for healthy eating interventions in a university specific setting. University characteristics (residency, exams, etc.) influence the relationships between individual as well as social environmental determinants and university students' eating behaviour, and should therefore be taken into account when designing effective and tailored multilevel intervention programs aiming to improve healthy eating behaviours in university students.

We aimed to analyze the characteristics of development of relative weight in Japanese triplets from birth until 12 years of age. Data were collected through a mailed questionnaire sent to mothers of triplets asking for information recorded in medical records. Altogether we had information on 1,061 triplet children of 354 mothers born between 1978 and 2006. For these births, data on triplets’ height and weight growth, gestational age, sex, parity, and maternal age at delivery were obtained from records in the maternal and child health handbooks and records from the schools where children receive health check-ups. In addition, information on maternal height and weight was obtained. Triplets have a lower ponderal index at birth and lower body mass index (BMI) compared with the general population until 12 years of age, except for the period during 1 and 3 years of age. Moreover, birth weight had the strongest contribution to BMI of triplets until 6 years of age. After 9 years of age, maternal BMI was a significant factor affecting BMI of triplets.

Increased body mass index (BMI) is a worldwide health issue. Individual differences in the susceptibility to increased BMI could be related to genes or environment. We performed a systematic review of genetic studies on BMI in pre-adolescence, young adulthood and late adulthood. We searched PubMed and EMBASE with heritability, body mass index, BMI, weight, height, anthropometry and twins as search terms. Studies reporting intra-pair correlations of healthy twin pairs that were raised together were included. This resulted in the inclusion of 8,179 monozygotic (MZ) and 9,977 dizygotic (DZ) twin pairs from twelve published studies in addition to individual participant data for 629 MZ and 594 DZ pairs from four twin registries. Structural equation modelling with intra-pair twin correlations showed that the heritability of BMI remained high over all age categories ranging from 61 % (95 % CI 54-64 %) to 80 % (95 % CI 76-81 %) for male and female subjects combined, while unique environmental influences increased from 14 % (95 % CI 13-15 %) to 40 % (95 % CI 37-43 %) with increasing age. Heritability of BMI remains consistently high over different age categories. Environmental changes over time do not seem to have as big a relative impact on an individual's weight as previously reported, suggesting a mainly genetic influence on variation in BMI over the years. © Springer-Verlag 2012.

Food choices established during childhood and adolescence tend to persist into adulthood with consequences for long-term health. Yet, to date, relatively little research has examined factors that influence the food choices of children and adolescents from their perspectives. In this article, previous research is extended by examining developmental differences between children's and adolescents' perceptions of factors influencing their food choices. Focus group discussions were conducted with 29 young people from three age groups (9-10, 13-14 and 16-18 years). An inductive thematic analysis identified three key factors as influencing food choices. These factors included intra-individual factors: the link between food preferences and awareness of healthy eating; intra-familial factors: the role of the home food environment; and extra-familial factors: eating away from the home. Findings indicate that there were developmental differences between children's and adolescents' perceptions of factors influencing food choice. Among adolescents, parental control began to diminish and adolescents exercised increased autonomy over their food choices compared with children. To develop effective nutrition interventions, it is important to gather child and adolescent input regarding factors perceived as influencing their food choices. Author has checked copyright DM, 12/12/2013

Background Previous studies of risk factors for disability pension (DP) have mainly focused on psychosocial, or environmental, factors, while the relative importance of genetic effects has been less studied. Sex differences in biological mechanisms have not been investigated at all. Methods The study sample included 46,454 Swedish twins, consisting of 23,227 complete twin pairs, born 1928–1958, who were followed during 1993–2008. Data on DP, including diagnoses, were obtained from the National Social Insurance Agency. Within-pair similarity in liability to DP was assessed by calculating intraclass correlations. Genetic and environmental influences on liability to DP were estimated by applying discrete-time frailty modeling. Results During follow-up, 7,669 individuals were granted DP (18.8% women and 14.1% men). Intraclass correlations were generally higher in MZ pairs than DZ pairs, while DZ same-sexed pairs were more similar than opposite-sexed pairs. The best-fitting model indicated that genetic factors contributed 49% (95% CI: 39–59) to the variance in DP due to mental diagnoses, 35% (95% CI: 29–41) due to musculoskeletal diagnoses, and 27% (95% CI: 20–33) due to all other diagnoses. In both sexes, genetic effects common to all ages explained one-third, whereas age-specific factors almost two-thirds, of the total variance in liability to DP irrespective of diagnosis. Sex differences in liability to DP were indicated, in that partly different sets of genes were found to operate in women and men, even though the magnitude of genetic variance explained was equal for both sexes. Conclusions The findings of the study suggest that genetic effects are important for liability to DP due to different diagnoses. Moreover, genetic contributions to liability to DP tend to differ between women and men, even though the overall relative contribution of genetic influences does not differ by sex. Hence, the pathways leading to DP might differ between women and men.

Background Previous studies, in late 20th century, suggest an increase in the prevalence of neck pain and low back pain among children and adolescents, when neck and low back pain were studied separately. This study investigated time trends in adolescent spinal pain between 1991 and 2011 by classifying pain into the following three classes: neck pain alone, low back pain alone, and concomitant neck and low back pain. Methods Representative samples of 12 to 18-year-old Finns were sent a questionnaire in 1991, 1999, 2001, 2003, 2005, 2007, 2009 and 2011. Information was gathered about the frequency of neck and low back pain with a six-month recall period. Statistical methods used included descriptive analysis, and generalized linear models. Results The total number of respondents in these eight comparable cross-sectional surveys was 51 044 with a response proportion of 64%. The prevalence of concomitant neck and low back pain showed a steady increase from 1991 to 2009/2011; the prevalence almost quadrupled among 12-14-year-olds girls (from 2% to 7.5%), and more than doubled among 12-14-year-old boys (from 1.6% to 3.8%), and among 16-18-year old boys (from 4.2 to 9.9%) and girls (6.9% to 15.9%). The prevalence of neck pain alone only increased in the 1990s (e.g. among 16-18-year-old girls 22.9% in 1991, 29.2% in 1999, and 29.5% in 2011), while the prevalence of low back pain alone remained relatively constant during the last two decades (e.g. among 16-18-year-old girls 4% in 1991, 3.1% in 1999, and 3.7% in 2011). Conclusions Concomitant neck and low back pain has constantly increased in the last two decades among adolescents, while single neck pain has only increased in the 1990s. Single low back pain has remained relatively constant. Thus, earlier detected increase in low back pain in the 1990s was explained by the increase in concomitant neck and low back pain. Differences in the time trends in the three pain conditions might suggest, at least partly, different risk factors and aetiology for single- and multisite spinal pain among adolescents. This hypothesis needs further investigations. Electronic supplementary material The online version of this article (doi:10.1186/1471-2474-15-296) contains supplementary material, which is available to authorized users.