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People with an evening (E)-type preference (ie, chronotype) experience musculoskeletal (MSK) pain and reduced health-related quality of life (HRQoL) more often than morning (M) types. Musculoskeletal pain is a well-established contributor to reduced HRQoL. This study aimed to evaluate whether eveningness amplifies the association between MSK pain and HRQoL in contrast to morningness. Questionnaire data on MSK pain dimensions (intensity, disability at work, number of pain sites [NPSs], and frequency), chronotype, covariates (sex, sufficiency of sleep duration, mental distress, and presence of coexisting diseases), and HRQoL (measured by 15D) were collected among 46-year-old individuals belonging to the Northern Finland Birth Cohort 1966 (N = 4257). Individuals without any MSK pain were excluded. General linear models were conducted to estimate the associations between chronotypes, MSK pain dimensions, and HRQoL. The interaction terms (chronotype x pain dimension) were tested in the models. There were 13% E-types and 43% M-types in the study sample. Each pain dimension and chronotype were related to HRQoL. In the sex-adjusted chronotype-specific models, the reduction in HRQoL in relation to pain appeared to be stronger among E-types than among M-types in respect to all pain dimensions. After adjustments, this was particularly seen in terms of NPS and pain frequency. Our findings suggest that eveningness intensifies the association between MSK pain and HRQoL, and, thus, they are indicative of E-types being more sensitive than M-types to the consequences of MSK pain. As such, MSK pain treatment and rehabilitation actions to improve HRQoL should be especially targeted at E-types.

Public Health Significance Both the amount of caffeine people consume and their response to caffeine is heritable. A modest proportion of the genetic influences underlying caffeine use and response is shared with personality and personality disorder traits. Our main aim was to estimate the extent of overlapping etiology between caffeine consumption and response and normative and pathological personality. Linear mixed-effects models were used to identify normative personality domains and personality disorder (PD) traits for inclusion in multivariate twin analyses together with individual caffeine related measures. Data were obtained from Norwegian adult twins in a face-to-face interview conducted in 1999-2004 as part of a population-based study of mental health and through self-report in 2010-2011 and 2015-2017. Personality disorder data was available for 2,793 twins, normative personality for 3,889 twins, and caffeine for 3,862 twins (mean age 43.0 years). Normative personality was assessed using the self-reported Big Five Inventory, PD traits were assessed by the Structured Interview for DSM-IV Personality, and caffeine consumption, toxicity, tolerance, and withdrawal were assessed through a self-report questionnaire developed at the Norwegian Institute of Public Health. Caffeine measures were found to be moderately heritable, h(2) = 30.1%-45.0%. All normative personality domains and four PD traits, antisocial, borderline, dependent and paranoid, were significantly associated with at least one caffeine variable. A small proportion of variance in caffeine consumption was attributable to genetic factors shared with normative personality (1.3%) and personality disorders (11.4%). A modest proportion of variance in caffeine tolerance and toxicity was attributable to genetic factors shared with both normative personality (26.9%, 24.8%) and personality disorders (21.0%, 36.0%). The present study found caffeine consumption and response to be heritable and provides evidence that a small to-modest proportion of this genetic etiology is shared with both normative and pathological personality.

Parent-of-origin effects (POE) and sex-specific parental effects have been reported for plasma lipid levels, and a strong relationship exists between dyslipidemia and obesity. We aim to explore whether genetic variants previously reported to have an association to lipid traits also show POE on blood lipid levels and obesity. Families from the Botnia cohort and the Hungarian Transdanubian Biobank (HTB) were genotyped for 12 SNPs, parental origin of alleles were inferred, and generalized estimating equations were modeled to assess parental-specific associations with lipid traits and obesity. POE were observed for the variants at the TMEM57, DOCK7/ANGPTL3, LPL, and APOA on lipid traits, the latter replicated in HTB. Sex-specific parental effects were also observed; variants at ANGPTL3/DOCK7 showed POE on lipid traits and obesity in daughters only, while those at LPL and TMEM57 showed POE on lipid traits in sons. Variants at LPL and DOCK7/ANGPTL3 showed POE on obesity-related traits in Botnia and HTB, and POE effects on obesity were seen to a higher degree in daughters. This highlights the need to include analysis of POEs in genetic studies of complex traits.

Analyses of the polygenic architecture of childhood, persistent and late-diagnosed attention-deficit hyperactivity disorder (ADHD) in a Danish population-based case-cohort sample identify differences among ADHD subgroups with respect to common and rare variants. Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder with onset in childhood (childhood ADHD); two-thirds of affected individuals continue to have ADHD in adulthood (persistent ADHD), and sometimes ADHD is diagnosed in adulthood (late-diagnosed ADHD). We evaluated genetic differences among childhood (n = 14,878), persistent (n = 1,473) and late-diagnosed (n = 6,961) ADHD cases alongside 38,303 controls, and rare variant differences in 7,650 ADHD cases and 8,649 controls. We identified four genome-wide significant loci for childhood ADHD and one for late-diagnosed ADHD. We found increased polygenic scores for ADHD in persistent ADHD compared with the other two groups. Childhood ADHD had higher genetic overlap with hyperactivity and autism compared with late-diagnosed ADHD and the highest burden of rare protein-truncating variants in evolutionarily constrained genes. Late-diagnosed ADHD had a larger genetic overlap with depression than childhood ADHD and no increased burden in rare protein-truncating variants. Overall, these results suggest a genetic influence on age at first ADHD diagnosis, persistence of ADHD and the different comorbidity patterns among the groups.

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.

Background The purpose of this study was to investigate if infants’ age at attaining motor developmental milestones is associated with the big five personality traits 50 years later. Methods Mothers of 8395 infants from the Copenhagen Perinatal Cohort recorded a total of 12 motor developmental milestones during the first year of their infant’s life. Information on at least one milestone was available for 1307 singletons with adult follow-up scores on the NEO-Five-Factor Inventory. The mean age at personality testing was 50.1 years. Results Slower attainment of motor milestones was associated with increased neuroticism and lower conscientiousness in midlife. All 12 motor developmental milestones explained a total of 2.4% of the variance in neuroticism, while they explained 3.2% of the variance in conscientiousness. These results remained significant after adjustment for the included family and perinatal covariates, as well as adult intelligence. Discussion The personality trait of neuroticism is a general risk factor for psychopathology and has in young adulthood been found to be associated with early motor development. However, evidence on associations of motor developmental milestones with other personality traits has been non-existent. These findings suggest that delays in early motor development may not only characterise individuals with later psychopathology, including schizophrenia, but may also be associated with personality traits such as neuroticism and conscientiousness through the life course.Keywords: motor developmental milestones; personality traits; birth cohort; NEO-Five-Factor Background The purpose of this study was to investigate if infants' age at attaining motor developmental milestones is associated with the big five personality traits 50 years later. Methods Mothers of 8395 infants from the Copenhagen Perinatal Cohort recorded a total of 12 motor developmental milestones during the first year of their infant's life. Information on at least one milestone was available for 1307 singletons with adult follow-up scores on the NEO-Five-Factor Inventory. The mean age at personality testing was 50.1 years. Results Slower attainment of motor milestones was associated with increased neuroticism and lower conscientiousness in midlife. All 12 motor developmental milestones explained a total of 2.4% of the variance in neuroticism, while they explained 3.2% of the variance in conscientiousness. These results remained significant after adjustment for the included family and perinatal covariates, as well as adult intelligence. Discussion The personality trait of neuroticism is a general risk factor for psychopathology and has in young adulthood been found to be associated with early motor development. However, evidence on associations of motor developmental milestones with other personality traits has been non-existent. These findings suggest that delays in early motor development may not only characterise individuals with later psychopathology, including schizophrenia, but may also be associated with personality traits such as neuroticism and conscientiousness through the life course.

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: Substantial evidence acknowledges the complex gene-environment interplay impacting brain development and learning. Intergenerational neuroimaging allows the assessment of familial transfer effects on brain structure, function and behavior by investigating neural similarity in caregiver-child dyads. Methods: Neural similarity in the human reading network was assessed through well-used measures of brain structure (i.e., surface area (SA), gyrification (lG), sulcal morphology, gray matter volume (GMV) and cortical thickness (CT)) in 69 mother-child dyads (children's age~11 y). Regions of interest for the reading network included left-hemispheric inferior frontal gyrus, inferior parietal lobe and fusiform gyrus. Mother-child similarity was quantified by correlation coefficients and familial specificity was tested by comparison to random adult-child dyads. Sulcal morphology analyses focused on occipitotemporal sulcus interruptions and similarity was assessed by chi-square goodness of fit. Results: Significant structural brain similarity was observed for mother-child dyads in the reading network for lG, SA and GMV (r = 0.349/0.534/0.542, respectively), but not CT. Sulcal morphology associations were non-significant. Structural brain similarity in lG, SA and GMV were specific to mother-child pairs. Furthermore, structural brain similarity for SA and GMV was higher compared to CT. Conclusion: Intergenerational neuroimaging techniques promise to enhance our knowledge of familial transfer effects on brain development and disorders., Developmental Cognitive Neuroscience, 53, ISSN:1878-9293, ISSN:1878-9307

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.

[EN] We analyzed the contribution of genetic factors on the association between puberty timing and body mass index (BMI) using longitudinal data and two approaches: (i) genetic twin design and (ii) polygenic scores (PGS) of obesity indices. Our data were derived from Finnish cohorts: 9080 twins had information on puberty timing and BMI and 2468 twins also had genetic data. Early puberty timing was moderately associated with higher BMI in childhood in both boys and girls; in adulthood these correlations were weaker and largely disappeared after adjusting for childhood BMI. The largest proportion of these correlations was attributable to genetic factors. The higher PGSs of BMI and waist circumference were associated with earlier timing of puberty in girls, whereas weaker associations were found in boys. Early puberty is not an independent risk factor for adult obesity but rather reflects the association between puberty timing and childhood BMI contributed by genetic predisposition. Open Access funding provided by University of Helsinki including Helsinki University Central Hospital. Data collection has been supported by National Institute of Alcohol Abuse and Alcoholism (Grants AA-12502, AA-00145, AA-09203, AA15416 and AA018755) and the Academy of Finland (Grants 100499, 118555, 141054, 264146, 308248 and 312073).

Co-twin comparisons address familial confounding by controlling for genetic and environmental influences that twin siblings share. We applied the co-twin comparison design to investigate associations of adolescent factors with alcohol dependence (AD) symptoms. Participants were 1286 individuals (581 complete twin pairs; 42% monozygotic; and 54% female) from the FinnTwin12 study. Predictors included adolescent academic achievement, substance use, externalizing problems, internalizing problems, executive functioning, peer environment, physical health, relationship with parents, alcohol expectancies, life events, and pubertal development. The outcome was lifetime AD clinical criterion count, as measured in young adulthood. We examined associations of each adolescent domain with AD symptoms in individual-level and co-twin comparison analyses. In individual-level analyses, adolescents with higher levels of substance use, teacher-reported externalizing problems at age 12, externalizing problems at age 14, self- and co-twin-reported internalizing problems, peer deviance, and perceived difficulty of life events reported more symptoms of AD in young adulthood (ps < .044). Conversely, individuals with higher academic achievement, social adjustment, self-rated health, and parent–child relationship quality met fewer AD clinical criteria (ps < .024). Associations between adolescent substance use, teacher-reported externalizing problems, co-twin-reported internalizing problems, peer deviance, self-rated health, and AD symptoms were of a similar magnitude in co-twin comparisons. We replicated many well-known adolescent correlates of later alcohol problems, including academic achievement, substance use, externalizing and internalizing problems, self-rated health, and features of the peer environment and parent–child relationship. Furthermore, we demonstrate the utility of co-twin comparisons for understanding pathways to AD. Effect sizes corresponding to the associations between adolescent substance use, teacher-reported externalizing problems, co-twin-reported internalizing problems, peer deviance, and self-rated health were not significantly attenuated (p value threshold = .05) after controlling for genetic and environmental influences that twin siblings share, highlighting these factors as candidates for further research.

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. Electronic supplementary material The online version of this article (10.1007/s10519-019-09960-z) contains supplementary material, which is available to authorized users.

BACKGROUND AND AIMS: Cannabis is one of the most commonly used substances among adolescents and young adults. Earlier age at cannabis initiation is linked to adverse life outcomes including multi-substance use and dependence. This study estimated the heritability of age at first cannabis use and identify associations with genetic variants.METHODS: A twin-based heritability analysis using 8,055 twins from three cohorts was performed. We then carried-out a genome wide survival meta-analysis of age at first cannabis use in a discovery sample of 24,953 individuals from nine European, North American, and Australian cohorts, and a replication sample of 3,735 individuals.RESULTS: The twin-based heritability for age at first cannabis use was 38% (95% confidence interval [CI] 19-60%). Shared and unique environmental factors explained 39% (95% CI 20-56%) and 22% (95% CI 16-29%). The genome wide survival meta-analysis identified five SNPs on chromosome 16 within the Calcium-transporting ATPase gene (ATP2C2) at P < 5E-08. All five SNPs are in high LD (r2 >0.8) with the strongest association at the intronic variant rs1574587 (P=4.09E-09). Gene-based tests of association identified the ATP2C2 gene on 16q24.1 (P=1.33e-06). Although the five SNPs and ATP2C2 did not replicate, ATP2C2 has been associated with cocaine dependence in a previous study. ATP2B2, which is a member of the same calcium signalling pathway, has been previously associated with opioid dependence. SNP-based heritability for age at first cannabis use was non-significant.CONCLUSION: Age at cannabis initiation appears to be moderately heritable in Western countries, and individual differences in onset can be explained by separate but correlated genetic liabilities. The significant association between age of initiation and ATP2C2 is consistent with the role of calcium signalling mechanisms in substance use disorders.

Poor sleep quality can have harmful health consequences. Although many aspects of sleep are heritable, the understandings of genetic factors involved in its physiology remain limited. Here, we performed a genome-wide association study (GWAS) using the Pittsburgh Sleep Quality Index (PSQI) in a multi-ethnic discovery cohort (n = 2868) and found two novel genome-wide loci on chromosomes 2 and 7 associated with global sleep quality. A meta-analysis in 12 independent cohorts (100 000 individuals) replicated the association on chromosome 7 between NPY and MPP6. While NPY is an important sleep gene, we tested for an independent functional role of MPP6. Expression data showed an association of this locus with both NPY and MPP6 mRNA levels in brain tissues. Moreover, knockdown of an orthologue of MPP6 in Drosophila melanogaster sleep center neurons resulted in decreased sleep duration. With convergent evidence, we describe a new locus impacting human variability in sleep quality through known NPY and novel MPP6 sleep genes.

Objective Associations of eveningness with health hazards benefit from analyzing to what extent the polygenic score for morningness correlates with the assessments of the behavioral trait of morningness-eveningness and chronotype. Methods With a population-based sample of 17,243 Finnish adults, aged 25–74 years, this study examines the associations of four feasible assessment methods of chronotype, a) biological the genetic liability based on the polygenic score for morningness (PGSmorn), b) the widely-used single item for self-assessed morningness/eveningness (MEQi19) of the original Morningness-Eveningness Questionnaire (MEQ), c) the behavioral trait of morningness-eveningness as assessed with the score on the shortened version (sMEQ) of the original MEQ, and d) the phase of entrainment as assessed with the habitual midpoint of sleep based on the self-reported sleep-wake schedule during weekend (Sleepmid-wknd) as well as the sleep debt corrected midpoint of sleep (Sleepmid-corr). Results All self-report measures correlated with each other, but very weakly with the PGSmorn, which explained 1–2% of the variation in diurnal preference or habitual sleep-wake schedule. The influence of age was greater on Sleepmid-wknd and Sleepmid-corr than on the sMEQ or MEQi19, indicating that the diurnal preference might be a more stable indicator for morningness-eveningness than the sleep-wake schedule. Analyses of the discrepancies between sMEQ and MEQi19 indicated that eveningness can be over-estimated when relying on only the single-item self-assessment. Conclusions The current polygenic score for morningness explains only a small proportion of the variation in diurnal preference or habitual sleep-wake schedule. The molecular genetic basis for morningness-eveningness needs further elucidation.

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.

Obesity has dramatically increased during the last decades and is currently one of the most serious global health problems. We present a hypothesis that obesity is a neuro-behavioral disease having a strong genetic background mediated largely by eating behavior and is sensitive to the macro-environment; we study this hypothesis from the perspective of genetic research. Genetic family and genome-wide-association studies have shown well that body mass index (BMI, kg/m(2)) is a highly heritable and polygenic trait. New genetic variation of BMI emerges after early childhood. Candidate genes of BMI notably express in brain tissue, supporting that this new variation is related to behavior. Obesogenic environments at both childhood family and societal levels reinforce the genetic susceptibility to obesity. Genetic factors have a clear influence on macro-nutrient intake and appetite-related eating behavior traits. Results on the gene-by-diet interactions in obesity are mixed, but emerging evidence suggests that eating behavior traits partly mediate the effect of genes on BMI. However, more rigorous prospective study designs controlling for measurement bias are still needed.

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 and aims: Cannabis is one of the most commonly used substances among adolescents and young adults. Earlier age at cannabis initiation is linked to adverse life outcomes, including multi-substance use and dependence. This study estimated the heritability of age at first cannabis use and identified associations with genetic variants. Methods: A twin-based heritability analysis using 8055 twins from three cohorts was performed. We then carried out a genome-wide association meta-analysis of age at first cannabis use in a discovery sample of 24 953 individuals from nine European, North American and Australian cohorts, and a replication sample of 3735 individuals. Results: The twin-based heritability for age at first cannabis use was 38% [95% confidence interval (CI) = 19–60%]. Shared and unique environmental factors explained 39% (95% CI = 20–56%) and 22% (95% CI = 16–29%). The genome-wide association meta-analysis identified five single nucleotide polymorphisms (SNPs) on chromosome 16 within the calcium-transporting ATPase gene (ATP2C2) at P 2 > 0.8), with the strongest association at the intronic variant rs1574587 (P = 4.09E-09). Gene-based tests of association identified the ATP2C2 gene on 16q24.1 (P = 1.33e-06). Although the five SNPs and ATP2C2 did not replicate, ATP2C2 has been associated with cocaine dependence in a previous study. ATP2B2, which is a member of the same calcium signalling pathway, has been associated previously with opioid dependence. SNP-based heritability for age at first cannabis use was non-significant. Conclusion: Age at cannabis initiation appears to be moderately heritable in western countries, and individual differences in onset can be explained by separate but correlated genetic liabilities. The significant association between age of initiation and ATP2C2 is consistent with the role of calcium signalling mechanisms in substance use disorders.

The purpose of this study was to identify, describe and conceptualize the present drivers of food choices and preferences of the Khwe San indigenous peoples by considering influences of their historical and cultural contexts. Data were collected in Eastern Bwabwata National Park in Namibia using a range of qualitative methods: semi-structured and structured interviews and free listing. The various drivers of food choices have been clustered into four levels of the ecological conceptual framework. Key factors, found to be driving participants' food choices, were the following: taste, hunger, health, familiarity and body satisfaction at the individual level; culture and food taboos at the social level; access to food and food storage at the physical level, and; cost and seasonality at the macro level. Many of these factors are directly related to food insecurity and previous experiences of hunger. Current preferences towards traditional foods existed but were not prevailing among all the participants. Interviews with the elderly revealed the historical context of the increasing exposure to modern foods and a contested access to traditional foods and traditional knowledge transmission. Our findings exposed some substantial gaps in the nutritional knowledge of the Khwe that need consideration by future health promotion strategies along with the current perceptions of local food choices. Ensuring access and promoting sustainable management of traditional foods would not only contribute to the health of the Khwe people but also help to maintain a nutritional safety net in their current situation of extreme poverty.

Twin studies have shown that emotional problems (anxiety and depression) in childhood and adolescence are moderately heritable (~20–50%). In contrast, DNA-based ‘SNP heritability’ estimates are generally

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.

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.

The purpose of the present study was to investigate the associations between personality facets and hypothalamic-pituitary-adrenal (HPA) axis functioning. Previous studies have mainly focussed on stress-induced HPA-axis activation. We hypothesized that other characteristics of HPA-axis functioning would have a stronger association with personality based on the neuroendocrine literature. Data (n=343) were used from the TRacking Adolescents' Individual Lives Survey (TRAILS), a large prospective cohort study of Dutch adolescents. We studied the association between facets of Neuroticism, Extraversion, and Conscientiousness and basal cortisol, the cortisol awakening response (CAR), and four measures of stress-induced HPA-axis activity. Basal cortisol levels were related to facets of all three personality traits. The CAR and stress-induced cortisol were not related to personality. Possibly due to its more trait-like nature, basal cortisol seems more informative than stress-induced cortisol when investigating trait-like characteristics such as personality facets.

Purpose: The period in which the transition to middle school occurs is marked by major changes in social context, social rules, and scholastic responsibilities. Some adolescents thrive during this period whereas others are overwhelmed and fail to cope adequately with their changing environment. We investigated basal cortisol upon waking as a predictor of change in mental health problems across the transition to middle school. By taking into account the transition experience, we extend prior findings that high basal cortisol predicts deteriorated mental health after the transition. In individuals with high awakening cortisol, we expected mental health problems to increase after negative transition experiences and to decrease after positive transition experiences, reflecting differential susceptibility. Evidence for the former but not the latter would suggest diathesis-stress.Methods: Data from 1,664 subjects were obtained from two measurement waves (mean ages, 11 and 13.5 years) of the TRacking Adolescents' Individual Lives Survey. Using linear regression, we investigated effects of awakening cortisol level, school transition experience, and their hypothesized interaction on change in mental health problems.Results: We found that a negative but not a positive experience was predictive of change in mental health. Importantly, our results showed that a negative experience predicts deteriorated mental health only in adolescents with high awakening cortisol but not in adolescents with low awakening cortisol. This finding was robust across informants. The converse, high awakening cortisol predicting decreasing mental health problems after a positive transition was not found.Conclusions: These results support the diathesis-stress model but not the differential susceptibility hypothesis. (c) 2015 Society for Adolescent Health and Medicine. All rights reserved.

Compelling evidence suggests that epigenetic mechanisms such as DNA methylation play a role in stress regulation and in the etiologic basis of stress related disorders such as Post traumatic Stress Disorder (PTSD). Here we describe the purpose and methods of an international consortium that was developed to study the role of epigenetics in PTSD. Inspired by the approach used in the Psychiatric Genomics Consortium, we brought together investigators representing seven cohorts with a collective sample size of N=1147 that included detailed information on trauma exposure, PTSD symptoms, and genome-wide DNA methylation data. The objective of this consortium is to increase the analytical sample size by pooling data and combining expertise so that DNA methylation patterns associated with PTSD can be identified. Several quality control and analytical pipelines were evaluated for their control of genomic inflation and technical artifacts with a joint analysis procedure established to derive comparable data over the cohorts for meta-analysis. We propose methods to deal with ancestry population stratification and type I error inflation and discuss the advantages and disadvantages of applying robust error estimates. To evaluate our pipeline, we report results from an epigenome-wide association study (EWAS) of age, which is a well-characterized phenotype with known epigenetic associations. Overall, while EWAS are highly complex and subject to similar challenges as genome-wide association studies (GWAS), we demonstrate that an epigenetic meta-analysis with a relatively modest sample size can be well-powered to identify epigenetic associations. Our pipeline can be used as a framework for consortium efforts for EWAS.

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.

Bipolar disorder (BPD) is associated with altered regional brain function during the performance of cognitive tasks. The relative contribution of genetic and environmental risk factors for BPD to these changes has not yet been quantified. We sought to address this issue in a functional neuroimaging study of people who varied in their risk for BPD. Functional magnetic resonance imaging was used to study 124 subjects (29 twin and 9 sibling pairs with at least one member with BPD, and 24 healthy twin pairs) performing a working memory task. We assessed the influence of risk for BPD on regional brain function during the task in a two stage process. Firstly, we identified areas where there were group differences in activation. Secondly, we estimated the heritability and phenotypic correlation of activation and BPD using genetic modeling. BPD was associated with increased activation in the anterior cingulate, orbitofrontal, medial prefrontal, and left precentral cortices, and in the precuneus. Within these regions, activation in the orbitofrontal cortex rendered the most significant heritability estimate (h(2)=0.40), and was significantly correlated with BPD phenotype (rph=0.29). A moderate proportion of the genetic influences (rg=0.69) acting on both BPD and on the degree of orbitofrontal activation were shared. These findings suggest that genetic factors that confer vulnerability to BPD alter brain function in BPD.

Early maturation, indexed by pubertal development (PD), has been associated with earlier initiation and greater frequency of adolescent substance use, but this relationship may be biased by confounding factors and effects that change across development. Using a population-based Finnish twin sample (N = 3,632 individuals), we conducted twin modeling and multilevel structural equation modeling of the relationship between PD and substance use at ages 12–22. Shared environmental factors contributed to early PD and heavier substance use for females. Biological father absence was associated with early PD for boys but not girls, and did not account for the relationship between PD and substance use. The association between early PD and heavier substance use was partially due to between-family confounds, although early PD appeared to qualitatively alter long-term trajectories for some substances (nicotine), but not others (alcohol). Mediation by peer and parental factors did not explain this relationship within families. However, higher peer substance use and lower parental monitoring were themselves associated with heavier substance use, strengthening the existing evidence for these factors as targets for prevention/intervention efforts. Early maturation was not supported as a robust determinant of alcohol use trajectories in adolescence and young adulthood, but may require longer term follow-up. Subtle effects of early PD on nicotine and illicit drug use trajectories throughout adolescence and adulthood merit further investigation.

Most adults are overweight or obese in many western countries. Several population-level interventions on the physical, economical, political, or sociocultural environment have thus attempted to achieve a healthier weight. These interventions have involved different weight-related behaviours, such as food behaviours. Agent-based models (ABMs) have the potential to help policymakers evaluate food behaviour interventions from a systems perspective. However, fully realizing this potential involves a complex procedure starting with obtaining and analyzing data to populate the model and eventually identifying more efficient cross-sectoral policies. Current procedures for ABMs of food behaviours are mostly rooted in one technique, often ignore the food environment beyond home and work, and underutilize rich datasets. In this paper, we address some of these limitations to better support policymakers through two contributions. First, via a scoping review, we highlight readily available datasets and techniques to deal with these limitations independently. Second, we propose a three steps' process to tackle all limitations together and discuss its use to develop future models for food behaviours. We acknowledge that this integrated process is a leap forward in ABMs. However, this long-term objective is well-worth addressing as it can generate robust findings to effectively inform the design of food behaviour interventions.

Intelligence is a core construct in differential psychology and behavioural genetics, and should be so in cognitive neuroscience. It is one of the best predictors of important life outcomes such as education, occupation, mental and physical health and illness, and mortality. Intelligence is one of the most heritable behavioural traits. Here, we highlight five genetic findings that are special to intelligence differences and that have important implications for its genetic architecture and for gene-hunting expeditions. (i) The heritability of intelligence increases from about 20% in infancy to perhaps 80% in later adulthood. (ii) Intelligence captures genetic effects on diverse cognitive and learning abilities, which correlate phenotypically about 0.30 on average but correlate genetically about 0.60 or higher. (iii) Assortative mating is greater for intelligence (spouse correlations similar to 0.40) than for other behavioural traits such as personality and psychopathology (similar to 0.10) or physical traits such as height and weight (similar to 0.20). Assortative mating pumps additive genetic variance into the population every generation, contributing to the high narrow heritability (additive genetic variance) of intelligence. (iv) Unlike psychiatric disorders, intelligence is normally distributed with a positive end of exceptional performance that is a model for 'positive genetics'. (v) Intelligence is associated with education and social class and broadens the causal perspectives on how these three inter-correlated variables contribute to social mobility, and health, illness and mortality differences. These five findings arose primarily from twin studies. They are being confirmed by the first new quantitative genetic technique in a century-Genome-wide Complex Trait Analysis (GCTA)-which estimates genetic influence using genome-wide genotypes in large samples of unrelated individuals. Comparing GCTA results to the results of twin studies reveals important insights into the genetic architecture of intelligence that are relevant to attempts to narrow the 'missing heritability' gap.

Gene-environment studies on adolescents' peer contexts are important for understanding the interplay between biological and social antecedents of adolescent psychopathology. To this end, this study examined the roles of serotonin transporter (5-HTTLPR) and preadolescent and early adolescent peer rejection and acceptance, as well as the interaction between genotype and environment as predictors of antisocial behavior. Longitudinal data from TRAILS (TRacking Adolescents' Individual Lives Survey), a Dutch cohort study into adolescent development that includes peer reports of rejection and acceptance assessed at 11.1 and 13.6 years and self-reported antisocial behavior at 19.1 years was used. The interaction between 5-HTTLPR and preadolescent peer rejection predicted antisocial behavior with carriers of the 5-HTTLPR short-short variant most strongly affected. No main or interaction effects were found for early adolescent rejection or interactions involving peer acceptance. Our results extend the gene-environment interaction literature by focusing on peer relationship experiences.

Childhood cruelty to animals is thought to indicate that a child may have been maltreated. This study examined: (a) prevalence of cruelty to animals among 5- to 12-year-old children; (b) the association between cruelty to animals, child physical maltreatment, and adult domestic violence; and (c) whether cruelty to animals is a marker of maltreatment taking into account age, persistence of cruelty, and socioeconomic disadvantage. Data were from the Environmental Risk (E-Risk) Longitudinal Twin Study, an epidemiological representative cohort of 2,232 children living in the United Kingdom. Mothers reported on cruelty to animals when children were 5, 7, 10, and 12 years, on child maltreatment up to age 12, and adult domestic violence. Nine percent of children were cruel to animals during the study and 2.6% persistently (>= 2 time-points). Children cruel to animals were more likely to have been maltreated than other children (OR = 3.32) although the majority (56.4%) had not been maltreated. Animal cruelty was not associated with domestic violence when maltreatment was controlled for. In disadvantaged families, 6 in 10 children cruel to animals had been maltreated. In other families, the likelihood of maltreatment increased with age (from 3 in 10 5-year-olds to 4.5 in 10 12-year-olds) and persistence (4.5 in 10 of those persistently cruel). Although childhood cruelty to animals is associated with maltreatment, not every child showing cruelty had been maltreated. The usefulness of cruelty to animals as a marker for maltreatment increases with the child's age, persistence of behavior, and poorer social background.

Background:In promoting physical activity, it is important to gain insight into environmental factors that facilitate or hinder physical activity and factors that may influence this environment–behavior relationship. As the personality factor of action orientation reflects an individual’s capacity to regulate behavior it may act as a moderator in the environment–behavior relationship. The current study addressed the relationship between neighborhood walkability and walking behavior and the influence of action orientation on this relationship.Methods:Three hundred and forty-seven Dutch inhabitants [mean age 43.1 (SD 17.1)] completed a web based questionnaire assessing demographic variables, neighborhood walkability (Neighborhood Environment Walkability Scale), variables of the Theory of Planned Behavior, action orientation, and walking behavior.Results:The results show that high levels of neighborhood walkability are positively associated with walking behavior and that this influence is largely unmediated by cognitive processes. A positive influence of neighborhood walkability on walking behavior was identified in the action-oriented subpopulation, whereas in the state-oriented part of the population, this influence was absent.Conclusions:The findings suggest that the influence of neighborhood environment on walking behavior has a relatively large unconscious, automatic component. In addition, the results suggest that the walkability–walking relationship is moderated by action orientation.

International audience; The aim of our study is to evaluate the validity of the "Caregiving x Temperament Paradigm" in the food domain. In this study, two prototypes of caregiving,control have been contrasted: Harsh (forceful measures to curve the child's behavior) versus Gentle control (supportive measures to direct the child's behavior). In food domain, the most effective control to help a child to overcome initial dislike is repeated exposure. Our first objective was to test whether the repeated exposure displayed in a gentle context has a more benefical effect on dislike shifting than the one displayed in a harsh context. Our second objective was to assess whether this effect was moderated by a temperamental characteristic (child's inhibitory control). A randomized experimental protocol was used in day care-centers, involving 98 children aged 21-41 months. Children were asked to consume an initially rejected target food on five occasions either with a Gentle or a Harsh instruction. Children's dislike for the target food was assessed via intake before and after the familiarization phase. Inhibitory control level was measured in 78 of these children using validated questionnaire. Four groups were created: Instructions (Gentle vs Harsh) x Inhibitory control (Lower vs Higher). After the familiarization phase, the consumption of the target food increased in all groups, but with a higher increase in children with high Inhibitory control with Gentle instruction, than for children with low Inhibitory control with Harsh instruction, the two other groups being in between. Our data fit a model of cumulative effects, and show that both gentle control strategies and high inhibitory control in children contribute to regulate disgusts experienced in some feeding contexts. (C) 2016 Elsevier Inc. All rights reserved.

Background: The differential susceptibly hypothesis suggests that certain genetic variants moderate the effects of both negative and positive environments on mental health and may therefore be important predictors of response to psychological treatments. Nevertheless, the identification of such variants has so far been limited to preselected candidate genes. In this study we extended the differential susceptibility hypothesis from a candidate gene to a genome-wide approach to test whether a polygenic score of environmental sensitivity predicted response to cognitive behavioural therapy (CBT) in children with anxiety disorders. Methods: We identified variants associated with environmental sensitivity using a novel method in which within-pair variability in emotional problems in 1,026 monozygotic twin pairs was examined as a function of the pairs' genotype. We created a polygenic score of environmental sensitivity based on the whole-genome findings and tested the score as a moderator of parenting on emotional problems in 1,406 children and response to individual, group and brief parent-led CBT in 973 children with anxiety disorders. Results: The polygenic score significantly moderated the effects of parenting on emotional problems and the effects of treatment. Individuals with a high score responded significantly better to individual CBT than group CBT or brief parent-led CBT (remission rates: 70.9, 55.5 and 41.6%, respectively). Conclusions: Pending successful replication, our results should be considered exploratory. Nevertheless, if replicated, they suggest that individuals with the greatest environmental sensitivity may be more likely to develop emotional problems in adverse environments but also benefit more from the most intensive types of treatment.

Little is known about the causes of individual differences in reward sensitivity. We investigated gene–environment interactions (GxE) on behavioral and neural measures of reward sensitivity, in light of the differential susceptibility theory. This theory states that individuals carrying plasticity gene variants will be more disadvantaged in negative, but more advantaged in positive environments. Reward responses were assessed during a monetary incentive delay task in 178 participants with and 265 without attention-deficit/hyperactivity disorder (ADHD), from N=261 families. We examined interactions between variants in candidate plasticity genes (DAT1, 5-HTT and DRD4) and social environments (maternal expressed emotion and peer affiliation). HTTLPR short allele carriers showed the least reward speeding when exposed to high positive peer affiliation, but the most when faced with low positive peer affiliation or low maternal warmth. DAT1 10-repeat homozygotes displayed similar GxE patterns toward maternal warmth on general task performance. At the neural level, DRD4 7-repeat carriers showed the least striatal activation during reward anticipation when exposed to high maternal warmth, but the most when exposed to low warmth. Findings were independent of ADHD severity. Our results partially confirm the differential susceptibility theory and indicate the importance of positive social environments in reward sensitivity and general task performance for persons with specific genotypes.