Personality and Smoking Status: A Longitudinal Analysis

We attempted to clarify the strength and nature of the association between personality and smoking status in early and middle adulthood, using a longitudinal study design. Data from the Medical Research Council National Survey of Health and Development, based on a stratified sample of all single, legitimate births occurring in England, Wales, and Scotland in one week of March 1946 (N=5,362), were analyzed using generalized estimating equations methods to account for the correlation between the smoking status variables for the same individual over time. The unadjusted estimates indicated that the odds of being a current smoker increased with higher personality score for both extraversion (p<.0001) and neuroticism (p<.0001) traits. Sex was significantly associated with being a current smoker (p<.0001), with males more likely than females to be current smokers. Current smoking decreased with increasing age (p<.0001). These relationships were maintained in the fully adjusted model. These data indicate that both higher levels of extraversion and higher levels of neuroticism, as measured at age 16, are independently associated with an increased likelihood of subsequently being a current smoker rather than a nonsmoker at all time points, although the observed effect sizes were small. Males also were more likely than females to be current smokers, and increasing age reduced the likelihood of being a current smoker, which is consistent with an attempt by a subset of smokers in the cohort to subsequently stop smoking

A functional genetic variation of the serotonin (5-HT) transporter affects 5-HT1A receptor binding in humans

In humans, 5-HT(1A) receptors are implicated in anxiety and depressive disorders and their treatment. However, the physiological and genetic factors controlling 5-HT(1A) receptor expression are undetermined in health and disease. In this study, the influence of two genetic factors on 5-HT(1A) receptor expression in the living human brain was assessed using the 5-HT(1A)-selective positron emission tomography (PET) ligand [ (11)C]WAY 100635. After the genotyping of 140 healthy volunteers to study population frequencies of known single nucleotide polymorphisms (SNPs) in the 5-HT(1A) receptor gene, the influence of the common SNP [(−1018) C>G] on 5-HT(1A) receptor expression was examined in a group of 35 healthy individuals scanned with [ (11)C]WAY 100635. In the PET group, we also studied the influence of a common variable number tandem repeat polymorphism [short (S) and long (L) alleles] of the 5-HT transporter (5-HTT) gene on 5-HT(1A) receptor density. Whereas, the 5-HT(1A) receptor genotype did not show any significant effects on [ (11)C]WAY 100635 binding, 5-HT(1A) receptor binding potential values were lower in all brain regions in subjects with 5-HTTLPR short (SS or SL) genotypes than those with long (LL) genotypes. Although the PET groups are necessarily a small sample size for a genetic association study, our results demonstrate for the first time that a functional polymorphism in the 5-HTT gene, but not the 5-HT(1A) receptor gene, affects 5-HT(1A) receptor availability in man. The results may offer a plausible physiological mechanism underlying the association between 5-HTTLPR genotype, behavioral traits, and mood states

Heavier smoking increases coffee consumption: Findings from a Mendelian randomization analysis

Background: There is evidence for a positive relationship between cigarette and coffee consumption in smokers. Cigarette smoke increases metabolism of caffeine, so this may represent a causal effect of smoking on caffeine intake. Methods: We performed Mendelian randomization analyses in the UK Biobank (N=114 029), the Norwegian HUNT study (N=56 664) and the Copenhagen General Population Study (CGPS) (N=78 650). We used the rs16969968 genetic variant as a proxy for smoking heaviness in all studies and rs4410790 and rs2472297 as proxies for coffee consumption in UK Biobank and CGPS. Analyses were conducted using linear regression and meta-analysed across studies. Results: Each additional cigarette per day consumed by current smokers was associated with higher coffee consumption (0.10 cups per day, 95% CI: 0.03, 0.17). There was weak evidence for an increase in tea consumption per additional cigarette smoked per day (0.04 cups per day, 95% CI: -0.002, 0.07). There was strong evidence that each additional copy of the minor allele of rs16969968 (which increases daily cigarette consumption) in current smokers was associated with higher coffee consumption (0.16 cups per day, 95% CI: 0.11, 0.20), but only weak evidence for an association with tea consumption (0.04 cups per day, 95% CI: -0.01, 0.09). There was no clear evidence that rs16969968 was associated with coffee or tea consumption in never or former smokers or that the coffeerelated variants were associated with cigarette consumption. Conclusions: Higher cigarette consumption causally increases coffee intake. This is consistent with faster metabolism of caffeine by smokers, but could also reflect a behavioural effect of smoking on coffee drinking

Corpus de techumbres mudéjares en Extremadura

Background: We aimed to estimate the causal effect of health conditions and risk factors on social and socioeconomic outcomes in UK Biobank. Evidence on socioeconomic impacts is important to understand because it can help governments, policy makers and decision makers allocate resources efficiently and effectively. Methods: We used Mendelian randomization to estimate the causal effects of eight health conditions (asthma, breast cancer, coronary heart disease, depression, eczema, migraine, osteoarthritis, type 2 diabetes) and five health risk factors [alcohol intake, body mass index (BMI), cholesterol, systolic blood pressure, smoking] on 19 social and socioeconomic outcomes in 336 997 men and women of White British ancestry in UK Biobank, aged between 39 and 72 years. Outcomes included annual household income, employment, deprivation [measured by the Townsend deprivation index (TDI)], degree-level education, happiness, loneliness and 13 other social and socioeconomic outcomes. Results: Results suggested that BMI, smoking and alcohol intake affect many socioeconomic outcomes. For example, smoking was estimated to reduce household income [mean difference = -£22 838, 95% confidence interval (CI): -£31 354 to -£14 321] and the chance of owning accommodation [absolute percentage change (APC) = -20.8%, 95% CI: -28.2% to -13.4%], of being satisfied with health (APC = -35.4%, 95% CI: -51.2% to -19.5%) and of obtaining a university degree (APC = -65.9%, 95% CI: -81.4% to -50.4%), while also increasing deprivation (mean difference in TDI = 1.73, 95% CI: 1.02 to 2.44, approximately 216% of a decile of TDI). There was evidence that asthma decreased household income, the chance of obtaining a university degree and the chance of cohabiting, and migraine reduced the chance of having a weekly leisure or social activity, especially in men. For other associations, estimates were null. Conclusions: Higher BMI, alcohol intake and smoking were all estimated to adversely affect multiple social and socioeconomic outcomes. Effects were not detected between health conditions and socioeconomic outcomes using Mendelian randomization, with the exceptions of depression, asthma and migraines. This may reflect true null associations, selection bias given the relative health and age of participants in UK Biobank, and/or lack of power to detect effects

From Men to Mice: CHRNA5/CHRNA3, Smoking Behavior and Disease

Introduction: The nicotinic acetylcholine receptor (nAChR) gene cluster CHRNA5-A3-B4 on chromosome 15 has been the subject of a considerable body of research over recent years. Two highly correlated single nucleotide polymorphisms (SNPs) within this region—rs16969968 in CHRNA5 and rs1051730 in CHRNA3—have generated particular interest. Methods: We reviewed the literature relating to SNPs rs16969968 and rs1051730 and smoking-related phenotypes, and clinical and preclinical studies, which shed light on the mechanisms underlying these associations. Results: Following the initial discovery of an association between this locus and smoking behavior, further associations with numerous phenotypes have been subsequently identified, including smoking-related behaviors, diseases, and cognitive phenotypes. Potential mechanisms thought to underlie these have also been described, as well as possible gene × environment interaction effects. Conclusions: Perhaps counter to the usual route of scientific inquiry, these initial findings, based exclusively on human samples and strengthened by their identification through agnostic genome-wide methods, have led to preclinical research focused on determining the mechanism underlying these associations. Progress has been made using knockout mouse models, highlighting the importance of α5 nAChR subunits in regulating nicotine intake, particularly those localized to the habenula–interpeduncular nucleus pathway. Translational research seeking to evaluate the effect of nicotine challenge on brain activation as a function of rs16969968 genotype using neuroimaging technologies is now called for, which may point to new targets for novel smoking cessation therapies

Guidelines for the use and interpretation of assays for monitoring autophagy

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field