Microbial liberation of N-methylserotonin from orange fiber in gnotobiotic mice and humans.

Plant fibers in byproduct streams produced by non-harsh food processing methods represent biorepositories of diverse, naturally occurring, and physiologically active biomolecules. To demonstrate one approach for their characterization, mass spectrometry of intestinal contents from gnotobiotic mice, plus in vitro studies, revealed liberation of N-methylserotonin from orange fibers by human gut microbiota members including Bacteroides ovatus. Functional genomic analyses of B. ovatus strains grown under permissive and non-permissive N-methylserotonin "mining" conditions revealed polysaccharide utilization loci that target pectins whose expression correlate with strain-specific liberation of this compound. N-methylserotonin, orally administered to germ-free mice, reduced adiposity, altered liver glycogenesis, shortened gut transit time, and changed expression of genes that regulate circadian rhythm in the liver and colon. In human studies, dose-dependent, orange-fiber-specific fecal accumulation of N-methylserotonin positively correlated with levels of microbiome genes encoding enzymes that digest pectic glycans. Identifying this type of microbial mining activity has potential therapeutic implications.

Evaluating microbiome-directed fibre snacks in gnotobiotic mice and humans.

Changing food preferences brought about by westernization that have deleterious health effects1,2-combined with myriad forces that are contributing to increased food insecurity-are catalysing efforts to identify more nutritious and affordable foods3. Consumption of dietary fibre can help to prevent cardiovascular disease, type 2 diabetes and obesity4-6. A substantial number of reports have explored the effects of dietary fibre on the gut microbial community7-9. However, the microbiome is complex, dynamic and exhibits considerable intra- and interpersonal variation in its composition and functions. The large number of potential interactions between the components of the microbiome makes it challenging to define the mechanisms by which food ingredients affect community properties. Here we address the question of how foods containing different fibre preparations can be designed to alter functions associated with specific components of the microbiome. Because a marked increase in snack consumption is associated with westernization, we formulated snack prototypes using plant fibres from different sustainable sources that targeted distinct features of the gut microbiomes of individuals with obesity when transplanted into gnotobiotic mice. We used these snacks to supplement controlled diets that were consumed by adult individuals with obesity or who were overweight. Fibre-specific changes in their microbiomes were linked to changes in their plasma proteomes indicative of an altered physiological state.

An approach for evaluating the effects of dietary fiber polysaccharides on the human gut microbiome and plasma proteome.

Increases in snack consumption associated with Westernized lifestyles provide an opportunity to introduce nutritious foods into poor diets. We describe two 10-wk-long open label, single group assignment human studies that measured the effects of two snack prototypes containing fiber preparations from two sustainable and scalable sources; the byproducts remaining after isolation of protein from the endosperm of peas and the vesicular pulp remaining after processing oranges for the manufacture of juices. The normal diets of study participants were supplemented with either a pea- or orange fiber-containing snack. We focused our analysis on quantifying the abundances of genes encoding carbohydrate-active enzymes (CAZymes) (glycoside hydrolases and polysaccharide lyases) in the fecal microbiome, mass spectrometric measurements of glycan structures (glycosidic linkages) in feces, plus aptamer-based assessment of levels of 1,300 plasma proteins reflecting a broad range of physiological functions. Computational methods for feature selection identified treatment-discriminatory changes in CAZyme genes that correlated with alterations in levels of fiber-associated glycosidic linkages; these changes in turn correlated with levels of plasma proteins representing diverse biological functions, including transforming growth factor type ß/bone morphogenetic protein-mediated fibrosis, vascular endothelial growth factor-related angiogenesis, P38/MAPK-associated immune cell signaling, and obesity-associated hormonal regulators. The approach used represents a way to connect changes in consumer microbiomes produced by specific fiber types with host responses in the context of varying background diets.

Genetic and Environmental Variation in Continuous Phenotypes in the ABCD Study®.

Twin studies yield valuable insights into the sources of variation, covariation and causation in human traits. The ABCD Study® (abcdstudy.org) was designed to take advantage of four universities known for their twin research, neuroimaging, population-based sampling, and expertise in genetic epidemiology so that representative twin studies could be performed. In this paper we use the twin data to: (i) provide initial estimates of heritability for the wide range of phenotypes assessed in the ABCD Study using a consistent direct variance estimation approach, assuring that both data and methodology are sound; and (ii) provide an online resource for researchers that can serve as a reference point for future behavior genetic studies of this publicly available dataset. Data were analyzed from 772 pairs of twins aged 9-10 years at study inception, with zygosity determined using genotypic data, recruited and assessed at four twin hub sites. The online tool provides twin correlations and both standardized and unstandardized estimates of additive genetic, and environmental variation for 14,500 continuously distributed phenotypic features, including: structural and functional neuroimaging, neurocognition, personality, psychopathology, substance use propensity, physical, and environmental trait variables. The estimates were obtained using an unconstrained variance approach, so they can be incorporated directly into meta-analyses without upwardly biasing aggregate estimates. The results indicated broad consistency with prior literature where available and provided novel estimates for phenotypes without prior twin studies or those assessed at different ages. Effects of site, self-identified race/ethnicity, age and sex were statistically controlled. Results from genetic modeling of all 53,172 continuous variables, including 38,672 functional MRI variables, will be accessible via the user-friendly open-access web interface we have established, and will be updated as new data are released from the ABCD Study. This paper provides an overview of the initial results from the twin study embedded within the ABCD Study, an introduction to the primary research domains in the ABCD study and twin methodology, and an evaluation of the initial findings with a focus on data quality and suitability for future behavior genetic studies using the ABCD dataset. The broad introductory material is provided in recognition of the multidisciplinary appeal of the ABCD Study. While this paper focuses on univariate analyses, we emphasize the opportunities for multivariate, developmental and causal analyses, as well as those evaluating heterogeneity by key moderators such as sex, demographic factors and genetic background.

Retrospectively assessed subjective effects of initial opioid use differ between opioid misusers with opioid use disorder (OUD) and those who never progressed to OUD: Data from a pilot and a replication sample.

Attempts to identify opioid users with increased risk of escalating to opioid use disorder (OUD) have had limited success. Retrospectively assessed subjective effects of initial opioid misuse were compared in a pilot sample of opioid misusers (nonmedical use ≤60 times lifetime) who had never met criteria for OUD (N = 14) and heroin-addicted individuals in treatment for OUD (N = 15). Relative to opioid misusers without a lifetime OUD diagnosis, individuals with OUD reported greater euphoria and other positive emotions, activation, pruritus, and internalizing symptoms. Consistent with these findings, proxy Addiction Research Center Inventory (ARCI) Amphetamine Group, and Morphine Benzedrine Group scale mean item scores were significantly higher in those with OUD. Replication was attempted in opioid misusers with (N = 25) and without OUD (N = 25) who were assessed as part of an ongoing genetic study. We observed similar significant between-group differences in individual subjective effect items and ARCI scale mean item scores in the replication sample. We, thus confirm findings from prior reports that retrospectively assessed subjective responses to initial opioid exposure differ significantly between opioid users who do, and do not, progress to OUD. Our report extends these findings in comparisons limited to opioid misusers. Additional research will be necessary to examine prospectively whether the assessment of subjective effects after initial use has predictive utility in the identification of individuals more likely to progress to OUD.

The roles of familial transmission and smoking during pregnancy on executive function skills: A sibling-comparison study.

This research examines maternal smoking during pregnancy and risk for poorer executive function in siblings discordant for exposure. Data (N = 173 families) were drawn from the Missouri Mothers and Their Children study, a sample, identified using birth records (years 1998-2005), in which mothers changed smoking behavior between two pregnancies (Child 1 [older sibling]: M age = 12.99; Child 2 [younger sibling]: M age = 10.19). A sibling comparison approach was used, providing a robust test for the association between maternal smoking during pregnancy and different aspects of executive function in early-mid adolescence. Results suggested within-family (i.e., potentially causal) associations between maternal smoking during pregnancy and one working memory task (visual working memory) and one response inhibition task (color-word interference), with increased exposure associated with decreased performance. Maternal smoking during pregnancy was not associated with stop-signal reaction time, cognitive flexibility/set-shifting, or auditory working memory. Initial within-family associations between maternal smoking during pregnancy and visual working memory as well as color-word interference were fully attenuated in a model including child and familial covariates. These findings indicate that exposure to maternal smoking during pregnancy may be associated with poorer performance on some, but not all skills assessed; however, familial transmission of risk for low executive function appears more important.

Meta-analysis of up to 622,409 individuals identifies 40 novel smoking behaviour associated genetic loci.

Smoking is a major heritable and modifiable risk factor for many diseases, including cancer, common respiratory disorders and cardiovascular diseases. Fourteen genetic loci have previously been associated with smoking behaviour-related traits. We tested up to 235,116 single nucleotide variants (SNVs) on the exome-array for association with smoking initiation, cigarettes per day, pack-years, and smoking cessation in a fixed effects meta-analysis of up to 61 studies (up to 346,813 participants). In a subset of 112,811 participants, a further one million SNVs were also genotyped and tested for association with the four smoking behaviour traits. SNV-trait associations with P < 5 × 10-8 in either analysis were taken forward for replication in up to 275,596 independent participants from UK Biobank. Lastly, a meta-analysis of the discovery and replication studies was performed. Sixteen SNVs were associated with at least one of the smoking behaviour traits (P < 5 × 10-8) in the discovery samples. Ten novel SNVs, including rs12616219 near TMEM182, were followed-up and five of them (rs462779 in REV3L, rs12780116 in CNNM2, rs1190736 in GPR101, rs11539157 in PJA1, and rs12616219 near TMEM182) replicated at a Bonferroni significance threshold (P < 4.5 × 10-3) with consistent direction of effect. A further 35 SNVs were associated with smoking behaviour traits in the discovery plus replication meta-analysis (up to 622,409 participants) including a rare SNV, rs150493199, in CCDC141 and two low-frequency SNVs in CEP350 and HDGFRP2. Functional follow-up implied that decreased expression of REV3L may lower the probability of smoking initiation. The novel loci will facilitate understanding the genetic aetiology of smoking behaviour and may lead to the identification of potential drug targets for smoking prevention and/or cessation.

Leveraging genome-wide data to investigate differences between opioid use vs. opioid dependence in 41,176 individuals from the Psychiatric Genomics Consortium.

To provide insights into the biology of opioid dependence (OD) and opioid use (i.e., exposure, OE), we completed a genome-wide analysis comparing 4503 OD cases, 4173 opioid-exposed controls, and 32,500 opioid-unexposed controls, including participants of European and African descent (EUR and AFR, respectively). Among the variants identified, rs9291211 was associated with OE (exposed vs. unexposed controls; EUR z = -5.39, p = 7.2 × 10-8). This variant regulates the transcriptomic profiles of SLC30A9 and BEND4 in multiple brain tissues and was previously associated with depression, alcohol consumption, and neuroticism. A phenome-wide scan of rs9291211 in the UK Biobank (N > 360,000) found association of this variant with propensity to use dietary supplements (p = 1.68 × 10-8). With respect to the same OE phenotype in the gene-based analysis, we identified SDCCAG8 (EUR + AFR z = 4.69, p = 10-6), which was previously associated with educational attainment, risk-taking behaviors, and schizophrenia. In addition, rs201123820 showed a genome-wide significant difference between OD cases and unexposed controls (AFR z = 5.55, p = 2.9 × 10-8) and a significant association with musculoskeletal disorders in the UK Biobank (p = 4.88 × 10-7). A polygenic risk score (PRS) based on a GWAS of risk-tolerance (n = 466,571) was positively associated with OD (OD vs. unexposed controls, p = 8.1 × 10-5; OD cases vs. exposed controls, p = 0.054) and OE (exposed vs. unexposed controls, p = 3.6 × 10-5). A PRS based on a GWAS of neuroticism (n = 390,278) was positively associated with OD (OD vs. unexposed controls, p = 3.2 × 10-5; OD vs. exposed controls, p = 0.002) but not with OE (p = 0.67). Our analyses highlight the difference between dependence and exposure and the importance of considering the definition of controls in studies of addiction.

Genetic and Environmental Influences on Perceived Social Support: Differences by Sex and Relationship.

Previous research has shown that self-reports of the amount of social support are heritable. Using the Kessler perceived social support (KPSS) measure, we explored sex differences in the genetic and environmental contributions to individual differences. We did this separately for subscales that captured the perceived support from different members of the network (spouse, twin, children, parents, relatives, friends and confidant). Our sample comprised 7059 male, female and opposite-sex twin pairs aged 18-95 years from the Australian Twin Registry. We found tentative support for different genetic mechanisms in males and females for support from friends and the average KPSS score of all subscales, but otherwise, there are no sex differences. For each subscale alone, the additive genetic (A) and unique environment (E) effects were significant. By contrast, the covariation among the subscales was explained - in roughly equal parts - by A, E and the common environment, with effects of different support constellations plausibly accounting for the latter. A single genetic and common environment factor accounted for between half and three-quarters of the variance across the subscales in both males and females, suggesting little heterogeneity in the genetic and environmental etiology of the different support sources.

Disruptive Behavior in Siblings Discordant for Exposure to Maternal Smoking During Pregnancy: A Multi-rater Approach.

INTRODUCTION: Maternal smoking during pregnancy (SDP) is associated with disruptive behavior. However, there is debate whether the SDP-disruptive behavior association is a potentially causal pathway or rather a spurious effect confounded by shared genetic and environmental factors. AIMS AND METHODS: The Missouri Mothers and Their Children Study is a sibling comparison study that includes families (n = 173) selected for sibling pairs (aged 7-16 years) discordant for SDP. Critically, the sibling comparison design is used to disentangle the effects of SDP from familial confounds on disruptive behavior. An SDP severity score was created for each child using a combination of SDP indicators (timing, duration, and amount of SDP). Multiple informants (parents and teachers) reported on disruptive behavior (i.e., DSM-IV semi-structured interview, the Child Behavior Checklist, and Teacher Report Form). RESULTS: The variability in disruptive behavior was primarily a function of within-family differences (66%-100%). Consistent with prior genetically informed approaches, the SDP-disruptive behavior association was primarily explained by familial confounds (genetic and environmental). However, when using a multi-rater approach (parents and teachers), results suggest a potentially causal effect of SDP on disruptive behavior (b = 0.09, SE = 0.04, p = 0.03). The potentially causal effect of SDP remained significant in sensitivity analyses. DISCUSSION: These findings suggest that familial confounding likely plays a complex role in the SDP-disruptive behavior association when examining both parent and teacher reports of behavior. Importantly, the current study highlights the importance of multiple raters, reflecting a more comprehensive measure of complex behaviors (e.g., disruptive behavior) to examine the teratogenic effects of SDP. IMPLICATIONS: Our study provides additional evidence that controlling for genetic and family factors is essential when examining the effect of SDP on later behavioral problems, as it explains a portion of the association between SDP and later behavioral problems. However, we found a significant association between SDP and disruptive behavior when using a multi-rater approach that capitalizes on both parent and teacher report, suggesting that parent and teacher ratings capture a unique perspective that is important to consider when examining SDP-behavior associations.

Genetic architecture of reciprocal social behavior in toddlers: Implications for heterogeneity in the early origins of autism spectrum disorder.

Impairment in reciprocal social behavior (RSB), an essential component of early social competence, clinically defines autism spectrum disorder (ASD). However, the behavioral and genetic architecture of RSB in toddlerhood, when ASD first emerges, has not been fully characterized. We analyzed data from a quantitative video-referenced rating of RSB (vrRSB) in two toddler samples: a community-based volunteer research registry (n = 1,563) and an ethnically diverse, longitudinal twin sample ascertained from two state birth registries (n = 714). Variation in RSB was continuously distributed, temporally stable, significantly associated with ASD risk at age 18 months, and only modestly explained by sociodemographic and medical factors (r2 = 9.4%). Five latent RSB factors were identified and corresponded to aspects of social communication or restricted repetitive behaviors, the two core ASD symptom domains. Quantitative genetic analyses indicated substantial heritability for all factors at age 24 months (h2 ≥ .61). Genetic influences strongly overlapped across all factors, with a social motivation factor showing evidence of newly-emerging genetic influences between the ages of 18 and 24 months. RSB constitutes a heritable, trait-like competency whose factorial and genetic structure is generalized across diverse populations, demonstrating its role as an early, enduring dimension of inherited variation in human social behavior. Substantially overlapping RSB domains, measurable when core ASD features arise and consolidate, may serve as markers of specific pathways to autism and anchors to inform determinants of autism's heterogeneity.

Trans-ethnic Fine Mapping Highlights Kidney-Function Genes Linked to Salt Sensitivity.

We analyzed genome-wide association studies (GWASs), including data from 71,638 individuals from four ancestries, for estimated glomerular filtration rate (eGFR), a measure of kidney function used to define chronic kidney disease (CKD). We identified 20 loci attaining genome-wide-significant evidence of association (p < 5 × 10(-8)) with kidney function and highlighted that allelic effects on eGFR at lead SNPs are homogeneous across ancestries. We leveraged differences in the pattern of linkage disequilibrium between diverse populations to fine-map the 20 loci through construction of "credible sets" of variants driving eGFR association signals. Credible variants at the 20 eGFR loci were enriched for DNase I hypersensitivity sites (DHSs) in human kidney cells. DHS credible variants were expression quantitative trait loci for NFATC1 and RGS14 (at the SLC34A1 locus) in multiple tissues. Loss-of-function mutations in ancestral orthologs of both genes in Drosophila melanogaster were associated with altered sensitivity to salt stress. Renal mRNA expression of Nfatc1 and Rgs14 in a salt-sensitive mouse model was also reduced after exposure to a high-salt diet or induced CKD. Our study (1) demonstrates the utility of trans-ethnic fine mapping through integration of GWASs involving diverse populations with genomic annotation from relevant tissues to define molecular mechanisms by which association signals exert their effect and (2) suggests that salt sensitivity might be an important marker for biological processes that affect kidney function and CKD in humans.

Shared and specific genetic risk factors for lifetime major depression, depressive symptoms and neuroticism in three population-based twin samples.

BACKGROUND: Vulnerability to depression can be measured in different ways. We here examine how genetic risk factors are inter-related for lifetime major depression (MD), self-report current depressive symptoms and the personality trait Neuroticism. METHOD: We obtained data from three population-based adult twin samples (Virginia n = 4672, Australia #1 n = 3598 and Australia #2 n = 1878) to which we fitted a common factor model where risk for 'broadly defined depression' was indexed by (i) lifetime MD assessed at personal interview, (ii) depressive symptoms, and (iii) neuroticism. We examined the proportion of genetic risk for MD deriving from the common factor v. specific to MD in each sample and then analyzed them jointly. Structural equation modeling was conducted in Mx. RESULTS: The best fit models in all samples included additive genetic and unique environmental effects. The proportion of genetic effects unique to lifetime MD and not shared with the broad depression common factor in the three samples were estimated as 77, 61, and 65%, respectively. A cross-sample mega-analysis model fit well and estimated that 65% of the genetic risk for MD was unique. CONCLUSION: A large proportion of genetic risk factors for lifetime MD was not, in the samples studied, captured by a common factor for broadly defined depression utilizing MD and self-report measures of current depressive symptoms and Neuroticism. The genetic substrate for MD may reflect neurobiological processes underlying the episodic nature of its cognitive, motor and neurovegetative manifestations, which are not well indexed by current depressive symptom and neuroticism.

Common genetic contributions to high-risk trauma exposure and self-injurious thoughts and behaviors.

BACKGROUND: Prior research has documented shared heritable contributions to non-suicidal self-injury (NSSI) and suicidal ideation (SI) as well as NSSI and suicide attempt (SA). In addition, trauma exposure has been implicated in risk for NSSI and suicide. Genetically informative studies are needed to determine common sources of liability to all three self-injurious thoughts and behaviors, and to clarify the nature of their associations with traumatic experiences. METHODS: Multivariate biometric modeling was conducted using data from 9526 twins [59% female, mean age = 31.7 years (range 24-42)] from two cohorts of the Australian Twin Registry, some of whom also participated in the Childhood Trauma Study and the Nicotine Addiction Genetics Project. RESULTS: The prevalences of high-risk trauma exposure (HRT), NSSI, SI, and SA were 24.4, 5.6, 27.1, and 4.6%, respectively. All phenotypes were moderately to highly correlated. Genetic influences on self-injurious thoughts and behaviors and HRT were significant and highly correlated among men [rG = 0.59, 95% confidence interval (CI) (0.37-0.81)] and women [rG = 0.56 (0.49-0.63)]. Unique environmental influences were modestly correlated in women [rE = 0.23 (0.01-0.45)], suggesting that high-risk trauma may confer some direct risk for self-injurious thoughts and behaviors among females. CONCLUSIONS: Individuals engaging in NSSI are at increased risk for suicide, and common heritable factors contribute to these associations. Preventing trauma exposure may help to mitigate risk for self-harm and suicide, either directly or indirectly via reductions in liability to psychopathology more broadly. In addition, targeting pre-existing vulnerability factors could significantly reduce risk for life-threatening behaviors among those who have experienced trauma.

Biomarker and Genomic Risk Factors for Liver Function Test Abnormality in Hazardous Drinkers.

BACKGROUND: Alcohol dependence and long-term excessive alcohol use may cause liver damage, but only some patients develop cirrhosis. Similarly, high alcohol intake without evident liver disease often but not always produces abnormal enzymatic liver function tests (LFTs), particularly gamma-glutamyl transferase (GGT). We postulate that the factors predisposing to cirrhosis in alcoholics and to liver enzyme abnormality in drinkers are similar, and that biochemical LFTs could therefore be useful as markers of risk of alcoholic liver disease in excessive drinkers. METHODS: Data from participants in twin and twin-family studies on alcohol use and dependence were used to identify 1,003 people who had reported excessive alcohol intake (28 drinks or more per week). A total of 962 of these provided blood for biochemical tests at the same time. Body mass index (BMI) and biomarkers of metabolic syndrome, inflammation, and iron stores were used in logistic regression with abnormality in serum GGT, alanine aminotransferase (ALT), or aspartate aminotransferase (AST) as outcomes. We conducted genome-wide association analyses for GGT, ALT, and AST separately in the group reporting excessive alcohol intake (N = 951) and a low-intake group reporting 14 drinks or fewer per week (N = 8,716), and compared results. RESULTS: Abnormal GGT and ALT among excessive drinkers were associated with higher BMI, triglycerides, insulin, uric acid, C-reactive protein, ferritin, and transferrin saturation; and with lower high-density-lipoprotein cholesterol. Abnormal AST was associated with triglycerides, ferritin, and transferrin saturation. ALT was significantly associated with variants at reported genetic loci for alcoholic liver disease (PNPLA3, rs738409, p = 0.0076; TM6SF2, rs10401969, p = 0.0076; HSD17B13, rs10433879, p = 0.0024). CONCLUSIONS: Known risk factors for alcoholic cirrhosis including obesity and markers of metabolic syndrome, iron overload and inflammation are associated with liver enzyme abnormality in excessive drinkers.

Quantifying between-cohort and between-sex genetic heterogeneity in major depressive disorder.

Major depressive disorder (MDD) is clinically heterogeneous with prevalence rates twice as high in women as in men. There are many possible sources of heterogeneity in MDD most of which are not measured in a sufficiently comparable way across study samples. Here, we assess genetic heterogeneity based on two fundamental measures, between-cohort and between-sex heterogeneity. First, we used genome-wide association study (GWAS) summary statistics to investigate between-cohort genetic heterogeneity using the 29 research cohorts of the Psychiatric Genomics Consortium (PGC; N cases = 16,823, N controls = 25,632) and found that some of the cohort heterogeneity can be attributed to ascertainment differences (such as recruitment of cases from hospital vs. community sources). Second, we evaluated between-sex genetic heterogeneity using GWAS summary statistics from the PGC, Kaiser Permanente GERA, UK Biobank, and the Danish iPSYCH studies but did not find convincing evidence for genetic differences between the sexes. We conclude that there is no evidence that the heterogeneity between MDD data sets and between sexes reflects genetic heterogeneity. Larger sample sizes with detailed phenotypic records and genomic data remain the key to overcome heterogeneity inherent in assessment of MDD.

Interactive Effects of Maternal Alcohol Problems and Parental Separation on Timing of Daughter's First Drink.

BACKGROUND: Few studies examine risk to offspring who experience both parental alcohol problems and parental separation and still fewer consider gender of the affected parent. We examined interactive effects of maternal versus paternal alcohol problems and parental separation on timing of first alcoholic drink in daughters. METHODS: Data were drawn from a sample of 3,539 European (or other) ancestry (EA) and 611 African ancestry (AA) female twins born between 1975 and 1985, median age 15 at first assessment. Cox proportional hazards regression models were estimated predicting age at first full drink from parental history of alcohol problems (mother only, father only, or both parents), parental separation during childhood, and the interaction of parental alcohol problems and parental separation. Cox models were estimated without and with adjustment for correlated risk factors, separately for EA and AA twins. RESULTS: For both EA and AA twins, a significant interaction between parental separation and mother-only alcohol problems was observed, suggesting reduced risk of drinking associated with mother-only alcohol problems in separated versus intact families. CONCLUSIONS: Findings highlight parental separation as an important moderator of risk to children of mothers who have a history of problem drinking, with interactive effects observed consistently across racial group. To identify underlying processes, additional research is needed with more detailed characterization of separated families where mother only has a history of alcohol problems.

Comparison of Characteristics of Female Drivers with Single and Multiple DUI Convictions.

BACKGROUND: Women are increasingly involved in drunk driving and fatal crashes, yet except for the screening performed in criminal justice settings, little is known about their life context, psychiatric histories, and family backgrounds. This study describes a sample of women with histories of arrest for driving under the influence of alcohol (DUI) who were interviewed outside a criminal justice setting and contrasts women with single versus multiple DUI convictions. METHODS: Women with recent documented histories of DUI participated in a study of women's health behaviors. Thirty-six women with 1 DUI and 62 with 2 or more DUIs participated in a diagnostic telephone interview which assessed demographics, alcohol use and problems, psychiatric problems, treatment, and partner violence. RESULTS: The sample overall had high rates of co-occurring psychiatric problems, parental alcohol problems, early sexual and physical abuse, and head injuries. Alcohol use severity and the prevalence of head injuries and partner alcohol problems were significantly higher among women with multiple DUIs than women with a single DUI. Measures reflecting life context, such as marital status, number of children, and childhood trauma, were not associated with number of DUIs. CONCLUSIONS: Findings suggest that DUI recidivism in women is accounted for primarily by AUD severity and is not influenced by previous life events such as partner violence, psychiatric problems, and family context such as divorce/separation or number of children. Multiple DUIs in women may mark an alcohol severity threshold beyond which few factors account for additional risk.

Human gut microbiome viewed across age and geography.

Gut microbial communities represent one source of human genetic and metabolic diversity. To examine how gut microbiomes differ among human populations, here we characterize bacterial species in fecal samples from 531 individuals, plus the gene content of 110 of them. The cohort encompassed healthy children and adults from the Amazonas of Venezuela, rural Malawi and US metropolitan areas and included mono- and dizygotic twins. Shared features of the functional maturation of the gut microbiome were identified during the first three years of life in all three populations, including age-associated changes in the genes involved in vitamin biosynthesis and metabolism. Pronounced differences in bacterial assemblages and functional gene repertoires were noted between US residents and those in the other two countries. These distinctive features are evident in early infancy as well as adulthood. Our findings underscore the need to consider the microbiome when evaluating human development, nutritional needs, physiological variations and the impact of westernization.