Subsample Of Twins Research Articles

Mosaic loss of Y chromosome and the association to mortality in Danish men aged 56–100 years

Mosaic loss of the Y chromosome (mLOY) is a common somatic mutation in the blood of elderly men and several studies have found mLOY in blood cells to be associated with an increased risk of various diseases and mortality. However, most of these studies have focused on middle-aged and older adults, meaning that mLOY in extremely old individuals like centenarians is understudied.To explore mLOY across a wider age range compared to earlier studies and to specifically focus on centenarians, mLOY was estimated in 917 Danish men aged 56–100 years. We found that the percentage of men with LOY increased with age until age 85, after which it plateaued at around 40 %. Consistently, a longitudinal comparison of mLOY revealed that mLOY predominantly increased with age, although inter-individual variation was seen. Using a twin sub-sample, the broad-sense heritability of mLOY was estimated at 72 %, indicating a substantial genetic influence.Supporting previous findings, mLOY was found to associate with increased mortality across all study participants and in men younger than 80 years. In centenarians, however, a higher level of mLOY associated with better survival, most likely due to selection, although confirmation of our findings in larger studies is needed.

Early life factors and individual differences in the brain through the human lifespan – association of intercept or change?

AbstractBackgroundHuman fetal development has been associated with brain health at later stages. In this presentation, I review results of analyses by the center for Lifespan Changes in Brain and cognition (LCBC), on whether and how consistently factors present in utero, including genetics (APOE4; polygenic risk for Alzheimer´s Disease; AD), prenatal drug exposure and, especially, growth in utero, as indexed by birth weight (BW), relates to lifespan brain characteristics and changes.MethodWe investigated associations between BW and cortical surface area, thickness and volume as derived from MRIs, across and within developmental, aging and lifespan longitudinal samples (N = 5794, 4‐82 years of age, w/ 386 monozygotic (MZ) twins, followed for up to 8.3 years w/12,088 brain MRIs).ResultsAssociations of BW and structural brain characteristics appear to be identifiable through the lifespan, with largely topographically consistent effects across samples of varying age. In developmental (ABCD), older adult and aging (UKB) and lifespan (LCBC) longitudinal samples, positive associations between BW and cortical surface area and volume were remarkably stable within and across samples of different age and origin, with spatial correlations in the range r = .51‐.79. In contrast, there was modest and no consistent effect of BW on brain changes. Effects of BW discordance in the twin subsample indicated the effects were partly environmental. This stable effect of an early life factor (BW), is similar to effects through the lifespan of genetic risk for AD, and persistent effects of prenatal opioid and ‐polydrug exposure in childhood and young adulthood.ConclusionThe influence of these early life factors, as here shown for BW, on brain topography, appear in part stable through the lifespan, being reliably seen in development, adulthood, and aging, as an intercept effect. These findings support early life influence on the brain through the lifespan according to a threshold model of brain reserve, rather than a maintenance model. To test experimentally whether early life factors may still influence slopes of brain and cognitive change, a navigation training neuroimaging study of twins with known extent of discordance in BW has been conducted, preliminary data from which is also presented.

The Heritability of Psychopathology Symptoms in Early Adolescence: Moderation by Family Cultural Values in the ABCD Study.

Family cultural values that emphasize support, loyalty, and obligation to the family are associated with lower psychopathology in Hispanic/Latino/a youth, but there is a need to understand the implications of family cultural values for youth development in racially/ethnically heterogeneous samples. This study examined phenotypic associations between parent- and youth-reported family cultural values in late childhood on youth internalizing and externalizing symptoms in early adolescence, and whether family cultural values moderated genetic and environmental influences on psychopathology symptoms. The sample comprised 10,335 children (Mage=12.89 years; 47.9% female; 20.3% Hispanic/Latino/a, 15.0% Black, 2.1% Asian, 10.5% other) and their parents from the Adolescent Brain Cognitive Development (ABCD) Study, and biometric models were conducted in the twin subsample (n = 1,042 twin pairs; 43.3% monozygotic). Parents and youth reported on their family cultural values using the Mexican American Cultural Values Scale at youth age 11-12, and parents reported on youth internalizing and externalizing symptoms using the Child Behavior Checklist at youth ages 11-12 and 12-13. Greater parent- and youth-reported family cultural values predicted fewer youth internalizing and externalizing symptoms. Biometric models indicated that higher parent-reported family cultural values increased the nonshared environmental influences on externalizing symptoms whereas youth-reported family cultural values decreased the nonshared environmental influences on internalizing symptoms. This study highlights the need for behavior genetic research to consider a diverse range of cultural contexts to better understand the etiology of youth psychopathology.

Testing Environmental Effects on Age at Menarche and Sexual Debut within a Genetically Informative Twin Design.

Life-history-derived models of female sexual development propose menarche timing as a key regulatory mechanism driving subsequent sexual behavior. The current research utilized a twin subsample of the National Longitudinal Study of Adolescent to Adult Health (Add Health; n = 514) to evaluate environmental effects on timings of menarche and sexual debut, as well as address potential confounding of these effects within a genetically informative design. Results show mixed support for each life history model and provide little evidence rearing environment is important in the etiology of individual differences in age at menarche. This research calls into question the underlying assumptions of life-history-derived models of sexual development and highlights the need for more behavior genetic research in this area.

Heritability Estimation of Cognitive Phenotypes in the ABCD Study® Using Mixed Models

Twin and family studies have historically aimed to partition phenotypic variance into components corresponding to additive genetic effects (A), common environment (C), and unique environment (E). Here we present the ACE Model and several extensions in the Adolescent Brain Cognitive Development℠ Study (ABCD Study®), employed using the new Fast Efficient Mixed Effects Analysis (FEMA) package. In the twin sub-sample (n = 924; 462 twin pairs), heritability estimates were similar to those reported by prior studies for height (twin heritability = 0.86) and cognition (twin heritability between 0.00 and 0.61), respectively. Incorporating SNP-derived genetic relatedness and using the full ABCD Study® sample (n = 9,742) led to narrower confidence intervals for all parameter estimates. By leveraging the sparse clustering method used by FEMA to handle genetic relatedness only for participants within families, we were able to take advantage of the diverse distribution of genetic relatedness within the ABCD Study® sample.

Parental feeding practices as a response to child appetitive traits in toddlerhood and early childhood: a discordant twin analysis of the Gemini cohort

BackgroundParental feeding practices (PFPs) have been implicated in the development of children’s eating behaviours. However, evidence suggests that feeding practices may also develop in response to their child’s weight or emerging appetitive traits. We used the twin design to test the hypothesis that parents develop their feeding practices partly in response to their child’s appetite.MethodsData were from Gemini, a population-based cohort of 2402 British families with twins born in 2007. Psychometric measures of PFPs and appetite were completed by parents when their twins were 16-months and 5-years. Within-family analyses including all twins with available data in the sample (n = 1010–1858 pairs), examined if within-pair differences in PFPs were associated with differences in appetitive traits, controlling for differences in birth weight-SDS, early feeding method and child sex. In a subsample of twin pairs who were considerably discordant for appetitive traits by ≥ 1SD (n = 122–544 pairs), the direction and magnitude of within-pair differences in feeding practices was explored.ResultsWithin-family variation in parental feeding practices in toddlerhood and early childhood was low (discordance ranged from 0.1 to 6% of the sample), except for pressure to eat (toddlerhood: 19%; early childhood: 32%). Within-pair differences in all appetitive traits were associated with differential use of ‘pressure to eat’ at both 16-months and 5-years. In the subsample of twins most discordant for appetitive traits, parents used more pressure with the twin expressing lower food responsiveness, lower emotional overeating, lower food enjoyment, higher satiety responsiveness, slower speed of eating, higher emotional undereating and greater fussiness in toddlerhood and early childhood (p-values < 0.001). Effect sizes were small to large at 16-months (η2=0.02–0.09) and 5-years (η2=0.05–0.21).ConclusionParents rarely varied their feeding practices between twins in toddlerhood and early childhood, except for pressure. Parents exerted greater pressure on their twin who expressed a poorer appetite compared to their co-twin, suggesting that parents develop a pressuring feeding style when their child expresses a poorer appetite or lower interest in, and enthusiasm for, eating. These findings could be used to guide interventions seeking to support parents in feeding their children in a way that nurtures the development of healthy eating behaviours.

Assessment of Mortality Disparities by Wealth Relative to Other Measures of Socioeconomic Status Among US Adults

The association between wealth and mortality is likely to be nonlinear and may result from selection and reverse causality. To compare the magnitude of mortality disparities by wealth relative to other measures of socioeconomic status (SES). This population-based cohort study began in 1995 to 1996, with approximately 18 years of mortality follow-up. These analyses were completed in November 2021. Data were derived from a population-based sample that targeted noninstitutionalized, English-speaking adults aged 25 to 74 years in the contiguous US. The response rate for the telephone interview ranged from 60% (twin subsample) to 70% (main sample). A self-administered questionnaire was completed by 89% of those interviewed by telephone. Net assets of the respondent and spouse or partner in 1995 to 1996. All-cause mortality. Among 6320 respondents (mean [SD] age at baseline, 46.9 [12.9] years; 3318 women [52.5%]), 1000 (15.8%) died by May 31, 2013. Adjusted for age, sex, and race, the mortality disparity by wealth was larger than the disparities by education, occupation, income, or childhood SES, especially at the oldest ages. After age 65 years, the hazard ratio [HR] was 2.69 (95% CI, 2.00-3.62) for those with no assets relative to those with at least $300 000 of wealth (in 1995 dollars), which translated into a 31 percentage point differential in estimated probability of surviving from age 65 years to 85 years (40% vs 71%). Additional wealth greater than $500 000 was not associated with lower mortality. In fully adjusted models, there was still a sizeable wealth disparity in mortality after age 65 years (HR, 1.89; 95% CI, 1.33-2.67). After adjustment for confounders, the estimated probability of surviving from age 65 to 85 years was 19 percentage points higher for persons with at least $300 000 in wealth (70%) than for those with no assets (51%), but there was a much larger 37 percentage point differential between never smokers (70%) and current smokers (33%). In this cohort study, the fully adjusted disparity in mortality associated with wealth beyond age 65 years remained sizeable but was much smaller than the smoking differential.

Gray matter volumetric correlates of dimensional impulsivity traits in children: Sex differences and heritability.

Previous research investigated the cerebral volumetric correlates of impulsivity largely in moderate‐sized samples and few have examined the distinct correlates of dimensions of impulsivity, sex differences, or heritability of the correlates. Here, we performed voxel‐based morphometry analysis of data (n = 11,474; 5,452 girls, 9–10 years) curated from the Adolescent Brain Cognition Development project. In a linear regression with all five UPPS‐P subscores as regressors and age in months, total intracranial volume, study site, and scanner model as covariates, higher levels of lack of premeditation, and sensation seeking were correlated with larger cortical and subcortical gray matter volumes (GMVs). In contrast, higher positive urgency was correlated with smaller GMVs in many of the same regions. The dimensional impulsivity traits also involved distinct volumetric correlates, with, for instance, sensation seeking and positive urgency specifically implicating bilateral caudate head/mid‐cingulate cortex and bilateral lateral orbitofrontal cortex/left precentral gyrus, respectively. Boys relative to girls scored higher in all impulsivity dimensions. Girls relative to boys showed significantly stronger positive and negative correlations between sensation seeking and insula, putamen, and inferior frontal gyrus (IFG) GMVs and between positive urgency and cingulate cortex, insula, and IFG GMVs, respectively. With a subsample of twins, the dimensional impulsivity traits were weakly to moderately heritable in both girls and boys, and the GMV correlates were highly heritable in girls and boys combined. These findings collectively suggest shared and nonshared as well as sex differences in the cerebral volumetric bases of dimensional impulsivity traits and may facilitate research of externalizing psychopathology in children.

Not Seeing Double: Discordance in Disease, Function, and Their Longitudinal Associations in Monozygotic Twins.

Prior research on the causality and directionality between disease and functional limitations is ambiguous. The current study used longitudinal monozygotic twin data to test both directions linking disease burden and functional limitations in middle-aged and older adults, controlling for genetic and familial factors. We also examined potential moderation by psychological well-being. The twin subsample from the first two waves of the longitudinal Midlife in the United States (MIDUS) study was used (wave 1, 1995-1996; wave 2, 2004-2006). Only monozygotic twins (n = 713) were included in analyses. In separate multilevel models, we examined disease burden at MIDUS 2 predicted by functional limitations at MIDUS 1 and MIDUS 2 functional limitations predicted by disease burden at MIDUS 1. Disease burden and functional limitations at MIDUS 2 varied substantially within families. There was no within-family association of earlier functional limitations with change in later disease burden (b = 0.40, p = .39), but there was a within-family association such that the twin with higher baseline disease burden had a greater increase in functional limitations than his/her co-twin (b = 0.06, p = .02). Well-being was not a moderator in either model. We found support for a potentially causal association between earlier disease burden and later increases in functional limitations, consistent with the Disablement Process Model. Sensitivity analyses confirm the detected within-family effect. Possible mechanisms linking disease burden and functional limitations are discussed as potential targets for future research.

The intersection of individual differences, personality variation, & military service: A twin comparison design

ABSTRACT In societies where military service is voluntary multiple factors are likely to affect the decision to enlist. Past research has produced evidence that a handful of personality and social factors seem to predict service in the military. However, recent quantitative genetic research has illustrated that enlistment in the military appears to be partially heritable and thus past research is potentially subject to genetic confounding. To assess the extent to which genetic confounding exists, the current study examined a wide range of individual-level factors using a subsample of twins (n = 1,232) from the restricted-use version of the National Longitudinal Study of Adolescent to Adult Health. The results of a series of longitudinal twin comparison models, which control for the latent sources of influence that cluster within families (i.e., shared genetic and family factors), illustrated generally null findings. However, individuals with higher scores on measures of extraversion and the general factor of personality were more likely to enlist in the military, after correction for familial confounding. Nonetheless, the overall results suggest that familial confounding should be a methodological concern in this area of research, and future work is encouraged to employ genetically informed methodologies in assessments of predictors of military enlistment.

Social-relational exposures and well-being: Using multivariate twin data to rule-out heritable and shared environmental confounds

The aims of the present study were as follows: (1) Using a large sample of adults, estimate overlap between social-relational exposures measured at midlife and well-being measured at midlife and approximately 9-years later. (2) Using a subsample of twins, test for heritable variation in social-relational exposures, and (3) controlling for heritable and shared environmental variation, estimate overlap between social-relational exposures and well-being, both concurrently and approximately 9-years later. Results indicated small-to-moderate overlap between exposures and well-being (mean r = 0.29, range = 0.05–0.54). There was also evidence for heritable variation in exposures, and after accounting for these genetic factors, the degree of overlap between social-relational exposures and well-being decreased (mean r = 0.10, range = −0.07 to 0.33).

Genetic Vulnerability to Experiencing Child Maltreatment.

Although biological factors may influence the risk of experiencing negative life events, the role of genes in the vulnerability to child victimization remains poorly understood. In a large population-based Finnish sample (N = 13,024), we retrospectively measured multiple experiences of child victimization and, in a subsample of twins (n = 9,562), we estimated the extent to which genetic and environmental factors influenced these experiences. In particular, we investigated whether genetic and environmental influences varied depending on the type of child victimization, the genetic relatedness with the perpetrator, and the sex of the victim. Our quantitative genetic analyses supported the presence of both genetic and environmental influences on the occurrence and co-occurrence of child abuse and neglect. We also identified one common etiological pathway underlying multiple child victimizations, and after accounting for this common etiology, we singled out risk factors specific to sexual abuse. Environmental factors shared and nonshared between twins raised together influenced the risk of victimization by genetically related and unrelated perpetrators, respectively. Furthermore, we estimated sex differences in the etiology of emotional and sexual victimization, including larger unshared environmental influences for men and sex-limited genetic effects for women. These findings can inform child protection as they contribute to explaining why certain individuals are at increased risk of experiencing one or more types of child maltreatment.

Mortality in parents after the death of a child

ObjectiveThe death of a child is a traumatic stressor that takes a toll on the health of parents. This study examined long-term impacts of the death of a child on the risk of early mortality in bereaved parents. In a follow-up analysis, a twin subsample was analyzed to examine potential genetic confounding. MethodWe analyzed data from the Midlife in the United States (MIDUS) study. The primary sample consists of two groups of MIDUS 2 participants (2004–06); (1) parents who experienced the death of a child prior to MIDUS 2 (n = 451) and (2) comparison parents who had not experienced death of any children (n = 1804) (mean age = 63). We also analyzed 52 twin pairs in which one twin experienced the death of a child and 271 twin pairs in which both twins had all living children. Mortality status of parents was assessed in 2017. ResultsParents who had experienced the death of a child had a 32% higher likelihood of early mortality (defined as dying earlier than life expectancy) than their peers who did not have any deceased children, and they were more likely to die of heart disease. Analyses of the twin subsample revealed significantly lower concordance for early mortality among the pairs with a bereaved twin than among control twins, consistent with non-genetic effects. ConclusionsThe findings suggest that the death of a child has lasting impacts on the risk of early mortality in bereaved parents. This study provides the first U.S. estimate of bereavement effects on mortality extending through the parents' full life course, with significant public health implications. In addition, analysis of concordance of early death rates in the twin subsample suggests the impact on mortality of parental bereavement, net of genetic factors.

S26. HERITABILITY OF SOCIAL MISTRUST IN CHILD AND ADOLESCENT NON-CLINICAL SAMPLES: A HEALTHY TWINS STUDY

BackgroundParanoia, or excessive suspiciousness of others, has been one of the core psychotic symptoms of schizophrenia. Recent studies have extended the study of psychotic symptoms in clinical groups to psychotic-like experiences in the general population. Few studies have systematically examined the prevalence of paranoid thinking or its attenuated form, social mistrust, in young children in the community. The present study examined the Social Mistrust Scale (SMS) and utilized it to examine the structure, prevalence, and heritability of social mistrust in a large sample of Chinese children and adolescents.MethodsWe administered the SMS to 1047 pairs of healthy twins aged 8 to 14 years and conducted structural equation modelling (SEM) to assess the structure of the SMS. Heritability of social mistrust was estimated in a sub-sample of twins (n=959 pairs). Finally, we examined administered the SMS to 32 adolescents with childhood-onset schizophrenia and 34 healthy controls to examine the convergent validity between the SMS and the Positive and Negative Syndrome Scale (PANSS).ResultsThe SEM showed a three-factor structure for social mistrust (home, school, and general mistrust). Social mistrust was moderately heritable (39%, 95% CI [21%-59%]) with context-dependent sex differences. The SMS exhibited good discriminant validity in distinguishing adolescents with childhood-onset schizophrenia from healthy controls (AUC=0.80), and good convergent validity with the Positive and Negative Syndrome Scale (rs = 0.33–0.45).DiscussionTaken together, the present findings showed a stable latent structure of the SMS in a large-scale non-clinical sample of children and adolescents. We found a moderate heritability estimate for social mistrust (39%) in a large healthy-twin sample. In addition, significant gender differences were found, where home mistrust was heritable for males (58%) but not for females, and school mistrust was heritable for females (54%) but not for males. Finally, we also demonstrated that the SMS possesses good discriminate validity in identifying adolescents with childhood-onset schizophrenia from healthy controls and convergent validity with standardized clinical measures of schizophrenia symptoms.

Suspiciousness in young minds: Convergent evidence from non-clinical, clinical and community twin samples

BackgroundWe validated the Social Mistrust Scale (SMS) and utilized it to examine the structure, prevalence, and heritability of social mistrust in a large sample of Chinese children and adolescents. MethodsIn Study 1, a large sample of healthy twins (N=2094) aged 8 to 14years (M=10.27years, SD=2) completed the SMS. Structural equation modeling (SEM) was conducted to assess the structure of the SMS and to estimate the heritability of social mistrust in a sub-sample of twins (n=756 pairs). In Study 2, 32 adolescents with childhood-onset schizophrenia were compared with 34 healthy controls on levels of suspiciousness and clinical symptoms to examine the associations between the SMS and the Positive and Negative Syndrome Scale (PANSS). ResultsWe found a three-factor structure for social mistrust (home, school, and general mistrust). Social mistrust was found to be moderately - heritable (19%–40%), with mistrust at home most strongly influenced by genetic factors. Compared with 11.76% of the healthy controls, 56.25% of the adolescents with early-onset schizophrenia exhibited very high levels of social mistrust on all three subscales of the SMS. The SMS exhibited good discriminant validity in distinguishing adolescents with childhood-onset schizophrenia from healthy controls and showed associations with a broad range of symptoms assessed by the PANSS. ConclusionsSocial mistrust assessed by the SMS may be heritable. The SMS demonstrates good discriminant validity with clinical diagnoses of schizophrenia. However, it seems to be correlated with multiple aspects of psychopathology in the schizophrenia group, rather than being specific to delusional ideation/paranoia.

Heritability of hoarding symptoms across adolescence and young adulthood: A longitudinal twin study.

BackgroundTwin studies of hoarding symptoms indicate low to moderate heritability during adolescence and considerably higher heritability in older samples, suggesting dynamic developmental etiological effects. The aim of the current study was to estimate the relative contribution of additive genetic and environmental effects to hoarding symptoms during adolescence and young adulthood and to estimate the sources of stability and change of hoarding symptoms during adolescence.MethodsUnivariate model-fitting was conducted in three cohorts of twins aged 15 (n = 7,905), 18 (n = 2,495) and 20–28 (n = 6,218). Longitudinal analyses were conducted in a subsample of twins for which data on hoarding symptoms was available at both age 15 and 18 (n = 1,701).ResultsHeritability estimates for hoarding symptoms at ages 15, 18 and 20–28 were 41% (95% confidence interval [CI]: 36–45%), 31% (95% CI: 22–39%) and 29% (95% CI: 24–34%) respectively. Quantitative sex-differences emerged in twins aged 15 at which point the heritability in boys was 33% (95% CI: 22–41%) and 17% (95% CI: 0–36%) in girls. Shared environmental effects played a negligible role across all samples with the exception of girls aged 15 where they accounted for a significant proportion of the variance (22%; 95% CI 6–36%). The longitudinal bivariate analyses revealed a significant phenotypic correlation of hoarding symptoms between ages 15 and 18 (0.40; 95% CI: 0.36–0.44) and a strong but imperfect genetic correlation (0.75; 95% CI: 0.57–0.94). The bivariate heritability was estimated to 65% (95% CI: 50–79%).ConclusionsHoarding symptoms are heritable from adolescence throughout young adulthood, although heritability appears to slightly decrease over time. Shared environmental effects contribute to hoarding symptoms only in girls at age 15. The stability of hoarding symptoms between ages 15 and 18 is largely explained by genetic factors, while non-shared environmental factors primarily have a time-specific effect. The findings indicate that dynamic developmental etiological effects may be operating across the life span.

Night work as a risk factor of future disability pension due to musculoskeletal diagnoses: a prospective cohort study of Swedish twins.

This study investigated the associations between night work, sleep and disability pension (DP) due to musculoskeletal disorders (MSD), while controlling for several confounding factors including both genetic factors and shared family background. The study sample consisted of 27 165 Swedish twin individuals born in 1935-58 with comprehensive survey data on sociodemographic, health and lifestyle factors. Night work was assessed as years of working hours at night at least every now and then, and categorized into 'not at all, 1-10 years and over 10 years'. Data on DP with MSD (ICD-diagnoses M00-M99) were obtained from the National Social Insurance Agency. Follow-up was from the time of the interview in 1998-2003 until 2013. Information on the length and quality of sleep was available for a sub-sample of twins (n = 1684). Cox proportional hazards models were used to calculate hazard ratios (HR) with 95% confidence intervals (CI). During the follow-up, 1338 (5%) participants were granted DP due to MSD. Both 1-10 years (HR 1.33, 95% CI 1.17-1.53) and over 10 years of night work (HR 1.39 95% CI 1.18-1.64) increased the risk of future DP. The associations were not affected by health, lifestyle or sleep factors. In the discordant twin pair analysis, the associations between night work and DP due to MSD attenuated. Night work was associated with increased risk of DP due to MSD independently from health and lifestyle factors. Familial confounding could not be ruled out.

Unstructured Socializing with Peers and Delinquent Behavior: A Genetically Informed Analysis

A large body of research finds that unstructured socializing with peers is positively associated with delinquency during adolescence. Yet, existing research has not ruled out the potential for confounding due to genetic factors and factors that can be traced to environments shared between siblings. To fill this void, the current study examines whether the association between unstructured socializing with peers and delinquent behavior remains when accounting for genetic factors, shared environmental influences, and a variety of non-shared environmental covariates. We do so by using data from the twin subsample of the National Longitudinal Study of Adolescent to Adult Health (n = 1200 at wave 1 and 1103 at wave 2; 51% male; mean age at wave 1 = 15.63). Results from both cross-sectional and lagged models indicate the association between unstructured socializing with peers and delinquent behavior remains when controlling for both genetic and environmental influences. Supplementary analyses examining the association under different specifications offer additional, albeit qualified, evidence supportive of this finding. The study concludes with a discussion highlighting the importance of limiting free time with friends in the absence of authority figures as a strategy for reducing delinquency during adolescence.

Heritable components of the human fecal microbiome are associated with visceral fat.

BackgroundVariation in the human fecal microbiota has previously been associated with body mass index (BMI). Although obesity is a global health burden, the accumulation of abdominal visceral fat is the specific cardio-metabolic disease risk factor. Here, we explore links between the fecal microbiota and abdominal adiposity using body composition as measured by dual-energy X-ray absorptiometry in a large sample of twins from the TwinsUK cohort, comparing fecal 16S rRNA diversity profiles with six adiposity measures.ResultsWe profile six adiposity measures in 3666 twins and estimate their heritability, finding novel evidence for strong genetic effects underlying visceral fat and android/gynoid ratio. We confirm the association of lower diversity of the fecal microbiome with obesity and adiposity measures, and then compare the association between fecal microbial composition and the adiposity phenotypes in a discovery subsample of twins. We identify associations between the relative abundances of fecal microbial operational taxonomic units (OTUs) and abdominal adiposity measures. Most of these results involve visceral fat associations, with the strongest associations between visceral fat and Oscillospira members. Using BMI as a surrogate phenotype, we pursue replication in independent samples from three population-based cohorts including American Gut, Flemish Gut Flora Project and the extended TwinsUK cohort. Meta-analyses across the replication samples indicate that 8 OTUs replicate at a stringent threshold across all cohorts, while 49 OTUs achieve nominal significance in at least one replication sample. Heritability analysis of the adiposity-associated microbial OTUs prompted us to assess host genetic-microbe interactions at obesity-associated human candidate loci. We observe significant associations of adiposity-OTU abundances with host genetic variants in the FHIT, TDRG1 and ELAVL4 genes, suggesting a potential role for host genes to mediate the link between the fecal microbiome and obesity.ConclusionsOur results provide novel insights into the role of the fecal microbiota in cardio-metabolic disease with clear potential for prevention and novel therapies.Electronic supplementary materialThe online version of this article (doi:10.1186/s13059-016-1052-7) contains supplementary material, which is available to authorized users.

Breastfeeding duration and offspring conduct problems: The moderating role of genetic risk

RationaleA sizable body of research has examined associations between breastfeeding and various facets of offspring development, including childhood behavioral problems. Notwithstanding the number of studies on the topic, breastfeeding has not consistently been linked to child misbehaviors. Moreover, empirical examinations of whether breastfeeding is differentially predictive of conduct problems among individuals with varying degrees of genetic risk are lacking. ObjectiveThe present study examines whether a short duration of breastfeeding and genetic risk interact to predict conduct problems during childhood. MethodsA genetically informative design is employed to examine a subsample of twins from the Early Childhood Longitudinal Study: Birth Cohort (ECLS-B), a nationally representative sample of American children. ResultsThe findings suggest that a shorter duration of breastfeeding only enhances the risk of offspring conduct problems among children who possess high levels of genetic risk. Conversely, longer breastfeeding durations were found to protect against childhood behavioral problems when genetic risk was high. ConclusionsIndicators of genetic risk may help to distinguish individuals whose behavioral development is most sensitive to the duration of breastfeeding. Future research should seek to replicate and extend these findings by considering genetic factors as potential markers of differential susceptibility to breastfeeding duration.