Social Determinants of Smoke Exposure During Pregnancy: Findings From Waves 1 & 2 of the Population Assessment of Tobacco and Health (PATH) Study

Maternal smoking during pregnancy (MSDP) and secondhand smoke (SHS) exposure are associated with a myriad of negative health effects for both mother and child. However, less is known regarding social determinants for SHS exposure, which may differ from those of maternal smoking during pregnancy (MSDP). To identify social determinants for SHS exposure only, MSDP only, and MSDP and SHS exposure, data were obtained from all pregnant women (18–54 years; N = 726) in waves 1 and 2 of the Population Assessment of Tobacco and Health Study (2014–2015). Multiple logistic regressions were conducted using SAS 9.4. Smoke exposure during pregnancy was common; 23.0% reported SHS exposure only, 6.1% reported MSDP only, and 11.8% reported both SHS exposure and MSDP. Results demonstrate that relationships between smoke exposure during pregnancy and social determinants vary by type of exposure. Women at risk for any smoke exposure during pregnancy include those who are unmarried and allow the use of combustible tobacco products within the home. Those who are at higher risk for SHS exposure include those who are younger in age, and those who are earlier in their pregnancy. Those who are at higher risk for maternal smoking include those with fair/poor mental health status and those who believe that others\u27 view tobacco use more positively. These results suggest the need for implementing more comprehensive policies that promote smoke-free environments. Implementing these strategies have the potential to improve maternal and fetal health outcomes associated with tobacco smoke exposure

Genetic and Environmental Influences on Smoking Behavior across Adolescence and Young Adulthood in the Virginia Twin Study of Adolescent Behavioral Development and the Transitions to Substance Abuse Follow-Up

Little is known regarding the underlying relationship between smoking initiation and current quantity smoked during adolescence into young adulthood. It is possible that the influences of genetic and environmental factors on this relationship vary across sex and age. To investigate this further, the current study applied a common causal contingency model to data from a Virginia-based twin study to determine: (1) if the same genetic and environmental factors are contributing to smoking initiation and current quantity smoked; (2) whether the magnitude of genetic and environmental factor contributions are the same across adolescence and young adulthood; and (3) if qualitative and quantitative differences in the sources of variance between males and females exist. Study results found no qualitative or quantitative sex differences in the relationship between smoking initiation and current quantity smoked, though relative contributions of genetic and environmental factors changed across adolescence and young adulthood. More specifically, smoking initiation and current quantity smoked remain separate constructs until young adulthood, when liabilities are correlated. Smoking initiation is explained by genetic, shared, and unique environmental factors in early adolescence and by genetic and unique environmental factors in young adulthood; while current quantity smoked is explained by shared environmental and unique environmental factors until young adulthood, when genetic and unique environmental factors play a larger role

White Matter Heritability Using Diffusion Tensor Imaging in Neonatal Brains

Understanding genetic and environmental effects on white matter development in the first years of life is of great interest, as it provides insights into the etiology of neurodevelopmental disorders. In this study, the genetic and environmental effects on white matter were estimated using data from 173 neonatal twin subjects. Diffusion tensor imaging scans were acquired around 40 days after birth and were non-rigidly registered to a group-specific atlas and parcellated into 98 ROIs. A model of additive genetic, and common and specific environmental variance components was used to estimate overall and regional genetic and environmental contributions to diffusion parameters of fractional anisotropy, radial diffusivity, and axial diffusivity. Correlations between the regional heritability values and diffusion parameters were also examined. Results indicate that individual differences in overall white matter microstructure, represented by the average diffusion parameters over the whole brain, are heritable, and estimates are higher than found in studies in adults. Estimates of genetic and environmental variance components vary considerably across different white matter regions. Significant positive correlations between radial diffusivity heritability and radial diffusivity values are consistent with regional genetic variation being modulated by maturation status in the neonatal brain: the more mature the region is, the less genetic variation it shows. Common environmental effects are present in a few regions that tend to be characterized by low radial diffusivity. Results from the joint diffusion parameter analysis suggest that multivariate modeling approaches might be promising to better estimate maturation status and its relationship with genetic and environmental effects

The Association between Loneliness with Increased Mental Health Problems and Substance Use During the COVID-19 Pandemic in Richmond, Virginia

Background. The COVID-19 pandemic caused significant psychological distress among U.S. adults leading to increased rates of adverse mental health symptoms and substance use. This study aims to evaluate the consistency of the association between loneliness and increased mental health problems and substance use in Richmond, VA during the COVID-19 pandemic. Methods. Data were collected in two phases: 1) internet-based surveys from August 2020 to March 2021 (N=327) and 2) paper-pencil surveys from May to October 2021 (N=225). Logistic regression was used to test the association between loneliness and increased mental health and substance use, while adjusting for sociodemographic factors and pre-existing mental health conditions. Results. Both survey populations reported a high prevalence of increased loneliness (46.7% - 68.8%), mental health problems (50.2% - 67.3%), and substance use (22.2% - 29.4%) since the COVID-19 pandemic. Increased loneliness since the pandemic was significantly associated with increased mental health problems (Online survey: AOR=5.00, 95% CI=2.56 - 9.97; Paper-pencil survey: AOR=10.48, 95% CI=4.18 - 28.59) and increased substance use (Online survey: AOR=3.14, 95% CI=1.58 - 6.60; Paper-pencil survey: AOR=5.89, 95% CI=1.97 - 19.71). Conclusions. The association between increased loneliness and increased mental health problems and substance use during COVID-19 in Richmond, Virginia was consistent across the two survey populations and similar to the rest of the U.S

A scoping review of smoking cessation pharmacogenetic studies to advance future research across racial, ethnic, and ancestral populations

Abstinence rates among smokers attempting to quit remain low despite the wide availability and accessibility of pharmacological smoking cessation treatments. In addition, the prevalence of cessation attempts and abstinence differs by individual-level social factors such as race and ethnicity. Clinical treatment of nicotine dependence also continues to be challenged by individual-level variability in effectiveness to promote abstinence. The use of tailored smoking cessation strategies that incorporate information on individual-level social and genetic factors hold promise, although additional pharmacogenomic knowledge is still needed. In particular, genetic variants associated with pharmacological responses to smoking cessation treatment have generally been conducted in populations with participants that self-identify as White race or who are determined to be of European genetic ancestry. These results may not adequately capture the variability across all smokers as a result of understudied differences in allele frequencies across genetic ancestry populations. This suggests that much of the current pharmacogenetic study results for smoking cessation may not apply to all populations. Therefore, clinical application of pharmacogenetic results may exacerbate health inequities by racial and ethnic groups. This scoping review examines the extent to which racial, ethnic, and ancestral groups that experience differences in smoking rates and smoking cessation are represented in the existing body of published pharmacogenetic studies of smoking cessation. We will summarize results by race, ethnicity, and ancestry across pharmacological treatments and study designs. We will also explore current opportunities and challenges in conducting pharmacogenomic research on smoking cessation that encourages greater participant diversity, including practical barriers to clinical utilization of pharmacological smoking cessation treatment and clinical implementation of pharmacogenetic knowledge

The Vaginal Microbiome: Disease, Genetics and the Environment

The vagina is an interactive interface between the host and the environment. Its surface is covered by a protective epithelium colonized by bacteria and other microorganisms. The ectocervix is nonsterile, whereas the endocervix and the upper genital tract are assumed to be sterile in healthy women. Therefore, the cervix serves a pivotal role as a gatekeeper to protect the upper genital tract from microbial invasion and subsequent reproductive pathology. Microorganisms that cross this barrier can cause preterm labor, pelvic inflammatory disease, and other gynecologic and reproductive disorders. Homeostasis of the microbiome in the vagina and ectocervix plays a paramount role in reproductive health. Depending on its composition, the microbiome may protect the vagina from infectious or non-infectious diseases, or it may enhance its susceptibility to them. Because of the nature of this organ, and the fact that it is continuously colonized by bacteria from birth to death, it is virtually certain that this rich environment evolved in concert with its microbial flora. Specific interactions dictated by the genetics of both the host and microbes are likely responsible for maintaining both the environment and the microbiome. However, the genetic basis of these interactions in both the host and the bacterial colonizers is currently unknown. _Lactobacillus_ species are associated with vaginal health, but the role of these species in the maintenance of health is not yet well defined. Similarly, other species, including those representing minor components of the overall flora, undoubtedly influence the ability of potential pathogens to thrive and cause disease. Gross alterations in the vaginal microbiome are frequently observed in women with bacterial vaginosis, but the exact etiology of this disorder is still unknown. There are also implications for vaginal flora in non-infectious conditions such as pregnancy, pre-term labor and birth, and possibly fertility and other aspects of women’s health. Conversely, the role of environmental factors in the maintenance of a healthy vaginal microbiome is largely unknown. To explore these issues, we have proposed to address the following questions:

*1.	Do the genes of the host contribute to the composition of the vaginal microbiome?* We hypothesize that genes of both host and bacteria have important impacts on the vaginal microbiome. We are addressing this question by examining the vaginal microbiomes of mono- and dizygotic twin pairs selected from the over 170,000 twin pairs in the Mid-Atlantic Twin Registry (MATR). Subsequent studies, beyond the scope of the current project, may investigate which host genes impact the microbial flora and how they do so.
*2.	What changes in the microbiome are associated with common non-infectious pathological states of the host?* We hypothesize that altered physiological (e.g., pregnancy) and pathologic (e.g., immune suppression) conditions, or environmental exposures (e.g., antibiotics) predictably alter the vaginal microbiome. Conversely, certain vaginal microbiome characteristics are thought to contribute to a woman’s risk for outcomes such as preterm delivery. We are addressing this question by recruiting study participants from the ~40,000 annual clinical visits to women’s clinics of the VCU Health System.
*3.	What changes in the vaginal microbiome are associated with relevant infectious diseases and conditions?* We hypothesize that susceptibility to infectious disease (e.g. HPV, _Chlamydia_ infection, vaginitis, vaginosis, etc.) is impacted by the vaginal microbiome. In turn, these infectious conditions clearly can affect the ability of other bacteria to colonize and cause pathology. Again, we are exploring these issues by recruiting participants from visitors to women’s clinics in the VCU Health System.

Three kinds of sequence data are generated in this project: i) rDNA sequences from vaginal microbes; ii) whole metagenome shotgun sequences from vaginal samples; and iii) whole genome shotgun sequences of bacterial clones selected from vaginal samples. The study includes samples from three vaginal sites: mid-vaginal, cervical, and introital. The data sets also include buccal and perianal samples from all twin participants. Samples from these additional sites are used to test the hypothesis of a per continuum spread of bacteria in relation to vaginal health. An extended set of clinical metadata associated with these sequences are deposited with dbGAP. We have currently collected over 4,400 samples from ~100 twins and over 450 clinical participants. We have analyzed and deposited data for 480 rDNA samples, eight whole metagenome shotgun samples, and over 50 complete bacterial genomes. These data are available to accredited investigators according to NIH and Human Microbiome Project (HMP) guidelines. The bacterial clones are deposited in the Biodefense and Emerging Infections Research Resources Repository ("http://www.beiresources.org/":http://www.beiresources.org/). 

In addition to the extensive sequence data obtained in this study, we are collecting metadata associated with each of the study participants. Thus, participants are asked to complete an extensive health history questionnaire at the time samples are collected. Selected clinical data associated with the visit are also obtained, and relevant information is collected from the medical records when available. This data is maintained securely in a HIPAA-compliant data system as required by VCU’s Institutional Review Board (IRB). The preponderance of these data (i.e., that judged appropriate by NIH staff and VCU’s IRB are deposited at dbGAP ("http://www.ncbi.nlm.nih.gov/gap":http://www.ncbi.nlm.nih.gov/gap). Selected fields of this data have been identified by NIH staff as ‘too sensitive’ and are not available in dbGAP. Individuals requiring access to these data fields are asked to contact the PI of this project or NIH Program Staff. 
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Associations between jet lag and cortisol diurnal rhythms after domestic travel.

Objective: Millions of adults in the United States travel abruptly across time zones each year. Nevertheless, the impact of traveling over relatively short distances (across 3 or fewer time zones) on diurnal patterning of typical physiological response patterns has yet to be studied in a large, epidemiological sample. Design: The current research focuses on 764 middle-aged men comparing variations in diurnal cortisol regulation based on number of time zones traveled eastward or westward the day before. Main Outcome Measure: Participants provided samples of salivary cortisol at waking, 30-min postwaking, 10 a.m., 3 p.m., and bedtime. Results: Eastward travel was associated with a steeper salivary cortiso

A Genetic Epidemiological Mega Analysis of Smoking Initiation in Adolescents

Introduction. Previous studies in adolescents were not adequately powered to accurately disentangle genetic and environmental influences on smoking initiation across adolescence. Methods. Mega-analysis of pooled genetically informative data on smoking initiation was performed, with structural equation modeling, to test equality of prevalence and correlations across cultural backgrounds, and to estimate the significance and effect size of genetic and environmental effects according to the classical twin study, in adolescent male and female twins from same-sex and opposite-sex twin pairs (N=19 313 pairs) between age 10 and 19, with 76 358 longitudinal assessments between 1983 and 2007, from 11 population-based twin samples from the US, Europe and Australia. Results. Although prevalences differed between samples, twin correlations did not, suggesting similar etiology of smoking initiation across developed countries. The estimate of additive genetic contributions to liability of smoking initiation increased from approximately 15% to 45% from age 13 to 19. Correspondingly, shared environmental factors accounted for a substantial proportion of variance in liability to smoking initiation at age 13 (70%) and gradually less by age 19 (40%). Conclusions. Both additive genetic and shared environmental factors significantly contribute to variance in smoking initiation throughout adolescence. The present study, the largest genetic epidemiological study on smoking initiation to date, found consistent results across 11 studies for the etiology of smoking initiation. Environmental factors, especially those shared by siblings in a family, primarily influence smoking initiation variance in early adolescence, while an increasing role of genetic factors is seen at later ages, which has important implications for prevention strategies. IMPLICATIONS: This is the first study to find evidence of genetic factors in liability to smoking initiation at ages as young as 12. It also shows the strongest evidence to date for decay of effects of the shared environment from early adolescence to young adulthood. We found remarkable consistency of twin correlations across studies reflecting similar etiology of liability to initiate smoking across different cultures and time periods. Thus familial factors strongly contribute to individual differences in who starts to smoke with a gradual increase in the impact of genetic factors and a corresponding decrease in that of the shared environment

Adult Romantic Attachment, Negative Emotionality, and Depressive Symptoms in Middle Aged Men: A Multivariate Genetic Analysis

Adult romantic attachment styles reflect ways of relating in close relationships and are associated with depression and negative emotionality. We estimated the extent to which dimensions of romantic attachment and negative emotionality share genetic or environmental risk factors in 1,237 middle-aged men in the Vietnam Era Twin Study of Aging (VETSA). A common genetic factor largely explained the covariance between attachment-related anxiety, attachment-related avoidance, depressive symptoms, and two measures of negative emotionality: Stress-Reaction (anxiety), and Alienation. Multivariate results supported genetic and environmental differences in attachment. Attachment-related anxiety and attachment-related avoidance were each influenced by additional genetic factors not shared with other measures; the genetic correlation between the attachment measure-specific genetic factors was 0.41, indicating some, but not complete overlap of genetic factors. Genetically informative longitudinal studies on attachment relationship dimensions can help to illuminate the role of relationship-based risk factors in healthy aging