CYP2A6 metabolism in the development of smoking behaviors in young adults.

Cytochrome P450 2A6 (CYP2A6) encodes the enzyme responsible for the majority of nicotine metabolism. Previous studies support that slow metabolizers smoke fewer cigarettes once nicotine dependent but provide conflicting results on the role of CYP2A6 in the development of dependence. By focusing on the critical period of young adulthood, this study examines the relationship of CYP2A6 variation and smoking milestones.

Monthly Estimates of Alcohol Drinking During Pregnancy: United States, 2002-2011.

Objective: Taking a step beyond prior alcohol research on pregnancy trimesters, we produced pregnancy month-specific drinking estimates for women in the United States in order to shed light on time variations of alcohol drinking during pregnancy, as might be determined by alcohol dependence. We posited that (a) pregnancy might prompt cessation of drinking soon after pregnancy status is discovered, a finding obscured in trimester-specific estimates, and (b) a possible alcohol-dependence effect on drinking persistence among pregnant women might be observed via the monthly approach.

Method: Data are from the 2002-2011 National Surveys on Drug Use and Health (Restricted-Data Analysis System [R-DAS]), with large nationally representative samples of U.

Birth weight and asthma incidence by asthma phenotype pattern in a racially diverse cohort followed through adolescence.

Objective: Low birth weight (LBW) has been shown to be an independent risk factor for asthma. We hypothesized that LBW would have its greatest impact on early onset disease.

Methods: A racially diverse cohort of children born from 1983 to 1985 at two hospitals, one urban and one suburban in the same metropolitan area, and oversampled for babies weighing ≤2500 g, was identified retrospectively when the children were 6 years of age and followed periodically.

Genetic variation (CHRNA5), medication (combination nicotine replacement therapy vs. varenicline), and smoking cessation.

Objective: Recent evidence suggests that the efficacy of smoking cessation pharmacotherapy can vary across patients based on their genotypes. This study tests whether the coding variant rs16969968 in the CHRNA5 nicotinic receptor gene predicts the effects of combination nicotine replacement therapy (cNRT) and varenicline on treatment outcomes.

Method: In two randomized smoking cessation trials comparing cNRT vs.

CHRNA5 risk variant predicts delayed smoking cessation and earlier lung cancer diagnosis--a meta-analysis.

Background: Recent meta-analyses show strong evidence of associations among genetic variants in CHRNA5 on chromosome 15q25, smoking quantity, and lung cancer. This meta-analysis tests whether the CHRNA5 variant rs16969968 predicts age of smoking cessation and age of lung cancer diagnosis.

Methods: Meta-analyses examined associations between rs16969968, age of quitting smoking, and age of lung cancer diagnosis in 24 studies of European ancestry (n = 29 072).

A non-parametric approach for detecting gene-gene interactions associated with age-at-onset outcomes.

Background: Cox-regression-based methods have been commonly used for the analyses of survival outcomes, such as age-at-disease-onset. These methods generally assume the hazard functions are proportional among various risk groups. However, such an assumption may not be valid in genetic association studies, especially when complex interactions are involved.

Multiple distinct CHRNB3-CHRNA6 variants are genetic risk factors for nicotine dependence in African Americans and European Americans.

Aims: Studies have shown association between common variants in the α6-β3 nicotinic receptor subunit gene cluster and nicotine dependence in European ancestry populations. We investigate whether this generalizes to African Americans, whether the association is specific to nicotine dependence and whether this region contains additional genetic contributors to nicotine dependence.

Design: We examined consistency of association across studies and race between the α6β3 nicotinic receptor subunit locus and nicotine, alcohol, marijuana and cocaine dependence in three independent studies.

Protocol for a collaborative meta-analysis of 5-HTTLPR, stress, and depression.

Background: Debate is ongoing about what role, if any, variation in the serotonin transporter linked polymorphic region (5-HTTLPR) plays in depression. Some studies report an interaction between 5-HTTLPR variation and stressful life events affecting the risk for depression, others report a main effect of 5-HTTLPR variation on depression, while others find no evidence for either a main or interaction effect. Meta-analyses of multiple studies have also reached differing conclusions.

Variants in two adjacent genes, EGLN2 and CYP2A6, influence smoking behavior related to disease risk via different mechanisms.

Genome-wide significant associations with cigarettes per day (CPD) and risk for lung cancer and chronic obstructive pulmonary disease (COPD) were previously reported in a region of 19q13, including CYP2A6 (nicotine metabolism enzyme) and EGLN2 (hypoxia response). The associated single nucleotide polymorphisms (SNPs) were assumed to be proxies for functional variation in CYP2A6. Here, we demonstrate that when CYP2A6 and EGLN2 genotypes are analyzed together, the key EGLN2 variant, rs3733829, is not associated with nicotine metabolism independent of CYP2A6, but is nevertheless independently associated with CPD, and with breath carbon monoxide (CO), a phenotype associated with cigarette consumption and relevant to hypoxia.

Assessing interchangeability at cluster levels with multiple-informant data.

Studies examining the relationship between neighborhood social disorder and health often rely on multiple informants. Such studies assume interchangeability of the latent constructs derived from multiple-informant data. Existing methods examining this assumption do not clearly delineate the uncertainty at individual levels from that at neighborhood levels.

The role of intelligence in posttraumatic stress disorder: does it vary by trauma severity?

Background: Only a small minority of trauma victims develops post-traumatic stress disorder (PTSD), suggesting that victims vary in their predispositions to the PTSD response to stressors. It is assumed that the role of predispositions in PTSD varies by trauma severity: when stressors are less severe, predispositions play a bigger role. In this study, we test whether the role of intelligence in PTSD varies by trauma severity.

Increased genetic vulnerability to smoking at CHRNA5 in early-onset smokers.

Context: Recent studies have shown an association between cigarettes per day (CPD) and a nonsynonymous single-nucleotide polymorphism in CHRNA5, rs16969968.

Objective: To determine whether the association between rs16969968 and smoking is modified by age at onset of regular smoking.

Data Sources: Primary data.

Interplay of genetic risk factors (CHRNA5-CHRNA3-CHRNB4) and cessation treatments in smoking cessation success.

Objective: Smoking is highly intractable, and the genetic influences on cessation are unclear. Identifying the genetic factors affecting smoking cessation could elucidate the nature of tobacco dependence, enhance risk assessment, and support development of treatment algorithms. This study tested whether variants in the nicotinic receptor gene cluster CHRNA5-CHRNA3-CHRNB4 predict age at smoking cessation and relapse after an attempt to quit smoking.

CHRNB3 is more strongly associated with Fagerström test for cigarette dependence-based nicotine dependence than cigarettes per day: phenotype definition changes genome-wide association studies results.

Aims: Nicotine dependence is a highly heritable disorder associated with severe medical morbidity and mortality. Recent meta-analyses have found novel genetic loci associated with cigarettes per day (CPD), a proxy for nicotine dependence. The aim of this paper is to evaluate the importance of phenotype definition (i.

Nicotine dependence and comorbid psychiatric disorders: examination of specific genetic variants in the CHRNA5-A3-B4 nicotinic receptor genes.

Background: The associations between nicotine dependence and specific variants in the nicotinic receptor CHRNA5-A3-B4 subunit genes are irrefutable with replications in many studies. The relationship between the newly identified genetic risk variants for nicotine dependence and comorbid psychiatric disorders is unclear. We examined whether these genetic variants were associated with comorbid disorders and whether comorbid psychiatric disorders modified the genetic risk of nicotine dependence.

Parental monitoring at age 11 and subsequent onset of cannabis use up to age 17: results from a prospective study.

Objective: Smoking cannabis before adulthood is associated with subsequent adverse psychiatric outcomes and might be prevented via parenting interventions such as programs to increase parents' effective monitoring of their children. The aim of this study was to estimate the influence of parental monitoring assessed at age 11 on the initiation of cannabis use before age 18.

Method: Data are from a longitudinal study of 823 children randomly selected from 1983 to 1985 newborn discharge lists from two major hospitals in southeast Michigan.

Dissection of the phenotypic and genotypic associations with nicotinic dependence.

Introduction: Strong evidence demonstrates that nicotine dependence is associated with 4 genetic variants rs16969968, rs6474412, rs3733829, and rs1329650 in large-scale Genome-Wide Association Studies. We examined how these identified genetic variants relate to nicotine dependence defined by different categorical and dimensional measures.

Methods: Four genetic variants were analyzed in 2,047 subjects of European descent (1,062 cases and 985 controls).

Rare missense variants in CHRNB4 are associated with reduced risk of nicotine dependence.

Genome-wide association studies have identified common variation in the CHRNA5-CHRNA3-CHRNB4 and CHRNA6-CHRNB3 gene clusters that contribute to nicotine dependence. However, the role of rare variation in risk for nicotine dependence in these nicotinic receptor genes has not been studied. We undertook pooled sequencing of the coding regions and flanking sequence of the CHRNA5, CHRNA3, CHRNB4, CHRNA6 and CHRNB3 genes in African American and European American nicotine-dependent smokers and smokers without symptoms of dependence.

DSM criteria for tobacco use disorder and tobacco withdrawal: a critique and proposed revisions for DSM-5.

Aims: This paper aims to identify appropriate criteria for tobacco dependence assessment, evaluate relevant research and suggest revisions that may be incorporated into DSM-5.

Methods: Desirable conceptual and psychometric features of tobacco dependence assessments were identified, including the types of outcomes against which such assessment should be validated. DSM-IV criteria were matched against these criteria and compared with other dependence measures.

Inclusion of African Americans in genetic studies: what is the barrier?

To facilitate an increase in the amount of data on minority subjects collected for genetic databases, the authors attempted to clarify barriers to African-American participation in genetic studies. They randomly sampled 78,072 subjects from the community (Missouri Family Registry, 2002-2007). Of these, 28,658 participated in a telephone screening interview, 3,179 were eligible to participate in the genetic study, and 1,919 participated in the genetic study.

Assessing the performance of the short screening scale for post‐traumatic stress disorder in a large nationally‐representative survey.

The performance of the short screening scale for the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM‐IV) post‐traumatic stress disorder (PTSD), has not been assessed in an independent general population sample, although it has been used in epidemiological as well as clinical research. In this report we evaluate the short screening scale in the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), a population‐based survey of US household and group quarter residents. DSM‐IV PTSD was assessed via symptom questions in the Alcohol Use Disorder and Associated Disabilities Interview Schedule‐DSM‐IV (AUDADIS‐IV) version.