The direction of causation between measures of disrupted sleep, anxiety and depression is not well understood. Under certain conditions, cross sectional analysis based on genetically informative data can provide important information about the direction of causation between variables. Two community-based samples of 7,235 Australian twins aged 18 to 87 years were mailed an extensive questionnaire that covered a wide range of personality and behavioral measures. Included were self-report measures of disrupted sleep as well as symptoms of anxiety and depression. Among all females, modeling the direction of causation did not support the hypothesis of sleep having a direct causal impact on risk of anxiety or depression. Among older females, we found evidence that both anxiety and depression interact reciprocally with disrupted sleep whereas among younger women, both anxiety and depression appear to have a causal impact on sleep. Results for males were equivocal. The nosological implications of our findings are discussed.
Disrupted sleep; anxiety; depression; twins; genes; environment; direction of causation
Variation in alcohol metabolism affects the duration of intoxication
and alcohol use. While the majority of genetic association studies
investigating variation in alcohol metabolism have focused on polymorphisms
in alcohol or aldehyde dehydrogenases, we have now tested for association
with genes in alternative metabolic pathways that catalyze the carbon
skeleton of ethanol and NADH reoxidation.
950 single nucleotide polymorphisms (SNPs) spanning 14 genes
(ACN9, ACSS1, ACSS2,
ALDH1A1, CAT, CYP2E1, GOT1,
GOT2, MDH1, MDH2,
SLC25A12, SLC25A13) were genotyped in
352 young adults who participated in an alcohol challenge study. Traits
tested were blood and breath alcohol concentration, peak alcohol
concentration and rates of alcohol absorption and elimination. Allelic
association was tested using quantitative univariate and multivariate
A CYP2E1 promoter SNP (rs4838767, minor allele
frequency 0.008) exceeded the threshold for study-wide significance (4.01
× 10−5) for two early blood alcohol concentration
(BAC), eight breath alcohol concentration (BrAC) measures and the peak BrAC.
For each phenotype the minor C-allele was related to a lower alcohol
concentration, most strongly for the fourth BrAC (P = 2.07 ×
10−7) explaining ~8% of the phenotypic
variance. We also observed suggestive patterns of association with variants
in ALDH1A1 and on chromosome 17 near
SLC25A11 for aspects of blood and breath alcohol
metabolism. A SNP upstream of GOT1 (rs2490286) reached
study-wide significance for multivariate BAC metabolism (P =
Overall, we did not find strong evidence that variation in genes
coding for proteins that further metabolize the carbon backbone of
acetaldehyde, or contribute to mechanisms for regenerating NAD from NADH,
affects alcohol metabolism in our European-descent subjects. However, based
on the breath alcohol data, variation in the promoter of
CYP2E1 may play a role in pre-absorptive or early
hepatic alcohol metabolism, but more samples are required to validate this
alcohol metabolism; association; genetics; CYP2E1; alcohol challenge
Schizotypy is phenotypically associated with neuroticism. To reveal the origin of this association, we assessed 3349 (1449 monozygotic (MZ), 1105 dizygotic (DZ) same-sex and 795 DZ opposite-sex) twins on a 12-item version of Chapman’s Psychosis-Proneness Scales and the short-form of the Eysenck Personality Questionnaire-Revised as measures of schizotypy and neuroticism.
A substantial proportion (.51 with 95% CI from .38 to .64) of the phenotypic correlation of .37 between neuroticism and the perceptual and ideational components of schizotypy was accounted for by shared genetic influences on these two traits. Moreover, a Cholesky decomposition including anhedonia, hypomania and impulsivity fully accounted for the heritable variance in perceptual and ideational components of schizotypy.
These findings suggest a shared genetic etiology between neuroticism and perceptual and ideational components of schizotypy and affect future investigations on the etiology of these phenotypically overlapping traits and affective and psychotic disorders.
Perceptual aberration; Magical ideation; Phenotypic correlation; Behavior genetics; Schizotypy; Neuroticism
This study sought to determine the relationship between BMI fluctuation and cardiovascular disease phenotypes, diabetes, and depression and the role of genetic and environmental factors in individual differences in BMI fluctuation using the extended twin-family model (ETFM).
Study Design and Methods
This study included 14,763 twins and their relatives. Health and Lifestyle Questionnaires were obtained from 28,492 individuals from the Virginia 30,000 dataset including twins, parents, siblings, spouses, and children of twins. Self-report cardiovascular disease, diabetes, and depression data were available. From self-reported height and weight, BMI fluctuation was calculated as the difference between highest and lowest BMI after age 18, for individuals 18–80 years. Logistic regression analyses were used to determine the relationship between BMI fluctuation and disease status. The ETFM was used to estimate the significance and contribution of genetic and environmental factors, cultural transmission, and assortative mating components to BMI fluctuation, while controlling for age. We tested sex differences in additive and dominant genetic effects, parental, non-parental, twin, and unique environmental effects.
BMI fluctuation was highly associated with disease status, independent of BMI. Genetic effects accounted for ~34% of variance in BMI fluctuation in males and ~43% of variance in females. The majority of the variance was accounted for by environmental factors, about a third of which were shared among twins. Assortative mating, and cultural transmission accounted for only a small proportion of variance in this phenotype.
Since there are substantial health risks associated with BMI fluctuation and environmental components of BMI fluctuation account for over 60% of variance in males and over 50% of variance in females, environmental risk factors may be appropriate targets to reduce BMI fluctuation.
BMI; Chronic Disease; Weight change; Heritability; Family Studies
Tobacco and alcohol are frequently used together, and this may be partly explained by a distinct profile of subjective effects associated with co-administration. Ecological Momentary Assessment studies have examined effects of naturally occurring co-use, but, to date, have not assessed differing effects as alcohol levels rise and fall.
To describe subjective states and appraisals of cigarette and alcohol effects reported during the entirety of real-world drinking episodes.
Currently-smoking frequent drinkers (N = 255) carried electronic diaries for 21 days. Analyses focused on reports made during 2,046 drinking episodes. Signaled prompts intensively oversampled moments in the hours following consumption of the first drink in an episode. Multilevel regression analyses were used to predict ratings of buzz, dizziness, excitement, and sluggishness as a function of person-level and contextual covariates, estimated blood alcohol concentration (eBAC) level, ascending vs. descending eBAC, smoking, and their interactions. Appraisals of cigarette and alcohol effects were also examined within this framework.
Buzz, excitement, and pleasure from alcohol and cigarettes were prominent features of real-world drinking episodes. Smoking was associated with enhanced buzz and excitement when eBAC was high and descending. Smoking slightly accentuated the relation between eBAC and ratings of drinking pleasure among women, but this relation was somewhat weakened by smoking among men.
Smoking during drinking episodes may be partly be explained by a persistence of stimulant alcohol effects beyond the BAC peak. Acute effects of nicotine and tobacco use on the descending limb deserve further scrutiny in experimental alcohol challenge research.
smoking; tobacco; alcohol; craving; reinforcement; subjective states; Ecological Momentary Assessment
To investigate the relative contribution of genetic and environmental factors on smoking trajectory membership and to test whether individual smoking trajectories represent phenotypic thresholds of increasing genetic risk along a common genetic liability dimension.
Prospective study of a birth cohort of female like-sex twin pairs.
Participants completed diagnostic interview surveys 4 times from adolescence (average age 16) through young adulthood (average age 25).
Female twins who had smoked ≥100 cigarettes lifetime (n=1466 regular smokers).
Number of cigarettes smoked per day during the heaviest period of smoking (2 waves) or during the past 12 months (2 waves).
A 4-trajectory class solution provided the best fit to cigarette consumption data and was characterized by Low (n=564, 38.47%), Moderate (n=366, 24.97%), and High level smokers (n=197, 13.44%), and smokers who increased their smoking from adolescence to young adulthood (n=339, 23.12%). The best genetic model fit was a 3-category model that comprised the Low, a combined Increasing + Moderate, and High trajectories. This trajectory categorization was heritable (72.7%) with no evidence for significant contribution from shared environmental factors.
The way that smoking patterns develop in adolescence has a high level of heritability.
smoking trajectories; twins; heritability
Although substance use is associated with reduced educational attainment, this association may be due to common risk factors such as socioeconomic disadvantage. We tested whether alcohol, nicotine, and illicit drug use and dependence were associated with lifetime educational attainment after controlling for familial background characteristics.
Data were from a 1987 questionnaire and a 1992 telephone diagnostic interview of 6242 male twins (n=3121 pairs; mean age= 41.9 years in 1992) who served in the U.S. military during the Vietnam-era, and therefore were eligible for educational benefits after military service. Reduced educational attainment (less than 16 years) was examined in twin pairs discordant for substance use history. Substance use and dependence risk factors assessed were early alcohol and cannabis use, daily nicotine use, lifetime cannabis use, and alcohol, nicotine, cannabis, and any illicit drug dependence.
Three significant differences were observed between at risk twins and their cotwins: Compared to their low-risk cotwins, likelihood of completing less than 16 years of education was significantly increased for: (a) twins who used alcohol before age 18 (adjusted OR=1.44; 95%CI:1.02–2.05), (b) twins with a lifetime alcohol dependence diagnosis (adjusted OR=1.76; 95%CI: 1.27–2.44), and (c) twins who had used nicotine daily for 30 or more days (adjusted OR=2.54, 95%CI: 1.55–4.17). However, no differences in education were observed among twin pairs discordant for cannabis initiation, early cannabis use, or cannabis, nicotine, or any illicit drug dependence.
Even in a veteran population with access to military educational benefits, early alcohol use, alcohol dependence, and daily nicotine use remained significantly associated with years of education after controlling for shared familial contributions to educational attainment. The association between other substances and educational attainment was explained by familial factors common to these substance use phenotypes and adult educational attainment.
cotwin-control design; early substance use; drug dependence; alcohol dependence; educational attainment
The endocannabinoid system has been implicated in stress adaptation and the regulation of mood in rodent studies, but few human association studies have examined these links and replications are limited.
To examine whether a synonymous polymorphism, rs1049353, in exon 4 of the gene encoding the human endocannabinoid receptor (CNR1) moderates the effect of self-reported childhood physical abuse on lifetime anhedonia and depression and further, to replicate this interaction in an independent sample.
Genetic association study in 1041 young adult U.S. women with replication in an independent Australian sample of 1428 heroin dependent cases and 506 neighborhood controls.
Main outcome measure
Self-reported anhedonia and depression (with anhedonia).
In both samples, those who experienced childhood physical abuse were considerably more likely to report lifetime anhedonia. However, in those with one or more copies of the minor allele of rs1049353, this pathogenic effect of childhood physical abuse was attenuated. Thus, in those reporting childhood physical abuse, while 57% of those homozygous for the major allele reported anhedonia, only 29% of those who were carriers of the minor allele reported it (p < 0.02). rs1049353 also buffered the effects of childhood physical abuse on major depressive disorder, however this influence was largely attributable to anhedonic depression. These effects were also noted in an independent sample, where minor allele carriers were at decreased risk for anhedonia even when exposed to physical abuse.
Consistent with preclinical findings, a synonymous CNR1 polymorphism, rs1049353, is linked to the effects of stress attributable to childhood physical abuse on anhedonia and anhedonic depression. This polymorphism reportedly resides in the neighborhood of an exon splice enhancer and hence, future studies should carefully examine its impact on expression and conformational variation in CNR1, particularly in relation to stress adaptation.
CNR1; endocannabinoid; physical abuse; rs1049353; GxE; anhedonia; major depression
The CHRNA5-CHRNA3-CHRNB4 gene cluster on chromosome 15q25.1 encoding the cholinergic nicotinic receptor subunits is robustly associated with smoking behavior and nicotine dependence. Only a few studies to date have examined the locus with alcohol related traits and found evidence of association with alcohol abuse and dependence. Our main goal was to examine the role of three intensively studied single nucleotide polymorphisms, rs16969968, rs578776 and rs588765, tagging three distinct loci, in alcohol use. Our sample was drawn from two independent Finnish population-based surveys, the National FINRISK Study and the Health 2000 (Health Examination) Survey. The combined sample included a total of 32,592 adult Finns (54% women) of whom 8,356 were assessed for cigarettes per day (CPD). Data on alcohol use were available for 31,812 individuals. We detected a novel association between rs588765 and alcohol use defined as abstainers and low-frequency drinkers versus drinkers (OR=1.15, p=0.00007). Additionally, we provide precise estimates of strength of the association between the three loci and smoking quantity in a very large population based sample. As a conclusion, our results provide further evidence for the nicotine-specific role of rs16969968 (locus 1). Further, our data suggest that the effect of rs588765 (locus 3) may be specific to alcohol use as the effect is seen also in never smokers.
Nicotinic acetylcholine receptors; 15q25.1; alcohol use; smoking behavior; public health; population-based sample; genetic association
While there is solid evidence that cannabis use is heritable, attempts to identify genetic influences at the molecular level have yielded mixed results. Here, a large twin family sample (N=7452) was used to test for association between ten previously reported candidate genes and lifetime frequency of cannabis use using a gene-based association test. None of the candidate genes reached even nominal significance (p<.05). The lack of replication may point to our limited understanding of the neurobiology of cannabis involvement and also to potential publication bias and false-positive findings in previous studies.
genes; cannabis; genetics; association
We present an approximate conditional and joint association analysis that can use summary-level statistics from a meta-analysis of genome-wide association studies (GWAS) and estimated linkage disequilibrium (LD) from a reference sample with individual-level genotype data. Using this method, we analyzed meta-analysis summary data from the GIANT Consortium for height and body mass index (BMI), with the LD structure estimated from genotype data in two independent cohorts. We identified 36 loci with multiple associated variants for height (38 leading and 49 additional SNPs, 87 in total) via a genome-wide SNP selection procedure. The 49 new SNPs explain approximately 1.3% of variance, nearly doubling the heritability explained at the 36 loci. We did not find any locus showing multiple associated SNPs for BMI. The method we present is computationally fast and is also applicable to case-control data, which we demonstrate in an example from meta-analysis of type 2 diabetes by the DIAGRAM Consortium.
Gays, lesbians, and bisexuals (i.e. nonheterosexuals) have been found to be at much greater risk for many psychiatric symptoms and disorders, including depression. This may be due in part to prejudice and discrimination experienced by nonheterosexuals, but studies controlling for minority stress, or performed in very socially liberal countries, suggest that other mechanisms must also play a role. Here we test the viability of common cause (shared genetic or environmental etiology) explanations of elevated depression rates in nonheterosexuals.
A community-based sample of adult twins (N=9884 individuals) completed surveys investigating the genetics of psychiatric disorder, and were also asked about their sexual orientation. Large subsets of the sample were asked about adverse childhood experiences such as sexual abuse, physical abuse, and risky family environment, and also about number of older brothers, paternal and maternal age, and number of close friends. Data were analysed using the classical twin design.
Nonheterosexual males and females had higher rates of lifetime depression than their heterosexual counterparts. Genetic factors accounted for 31% and 44% of variation in sexual orientation and depression, respectively. Bivariate analysis revealed that genetic factors accounted for a majority (60%) of the correlation between sexual orientation and depression. In addition, childhood sexual abuse and risky family environment were significant predictors of both sexual orientation and depression, further contributing to their correlation.
Nonheterosexual men and women had elevated rates of lifetime depression, partly due to shared etiological factors, although causality cannot be definitively resolved.
sexual orientation; childhood abuse; depression; twins; genetics
Understanding the relative contributions of genetic and environmental factors to trauma exposure, post-traumatic stress disorder (PTSD), and major depressive disorder (MDD) is critical to developing etiologic models of these conditions and their co-occurrence.
To quantify heritable influences on low-risk trauma, high-risk trauma, PTSD, and MDD and to estimate the degree of overlap between genetic and environmental sources of variance in these 4 phenotypes.
Adult twins and their siblings were ascertained from a large population-based sample of female and male twin pairs on the basis of screening items for childhood sexual abuse and physical abuse obtained in a previous assessment of this cohort.
Structured psychiatric telephone interviews.
Total sample size of 2591: 996 female and 536 male twins; 625 female and 434 male nontwin siblings.
Main Outcome Measure
Lifetime low- and high-risk trauma exposure, PTSD, and MDD.
In the best-fitting genetic model, 47% of the variance in low-risk trauma exposure and 60% of the variance in high-risk trauma exposure was attributable to additive genetic factors. Heritable influences accounted for 46% of the variance in PTSD and 27% of the variance in MDD. An extremely high degree of genetic overlap was observed between high-risk trauma exposure and both PTSD (r =0.89; 95% CI, 0.78-0.99) and MDD (r =0.89; 95% CI, 0.77-0.98). Complete correlation of genetic factors contributing to PTSD and to MDD (r=1.00) was observed.
The evidence suggests that almost all the heritable influences on high-risk trauma exposure, PTSD, and MDD, can be traced to the same sources; that is, genetic risk is not disorder specific. Individuals with a positive family history of either PTSD or MDD are at elevated risk for both disorders and should be closely monitored after a traumatic experience for symptoms of PTSD and MDD.
The development of alcohol dependence (AD) involves transitions through multiple stages of drinking behaviors and is shaped by both heritable and environmental influences. We attempted to capture this dynamic process by characterizing genetic and environmental contributions to the rate at which women progressed through 3 significant transitions along the pathway to AD: nonuse to initiation, initiation to onset of first alcohol-related problem, and first problem to onset of AD.
The sample consisted of 3,546 female twins from the Missouri Adolescent Female Twin Study. Participants ranged in age from 18 to 29 years. Retrospective reports of alcohol use histories were collected by telephone diagnostic interview and transition times between drinking milestones were coded ordinally. Standard genetic analyses were conducted in Mx to derive a trivariate model that provided estimates of genetic and environmental influences that were common as well as specific to the 3 transition times.
Heritable influences were found for rate of progression across all 3 transitions, accounting for 30 to 47% of the variance in transition times. Shared environmental contributions were evident only in rate of progression from nonuse to initiation (i.e., age at first drink). Heritable contributions to the rate of movement through successive drinking milestones were attributable to a common factor, whereas environmental influences were transition-specific.
The current study is unique in its use of a genetically informative design to document the rate of movement between drinking milestones in a female sample and to examine genetic contributions to multiple transition times over the course of AD development. Results indicate that an earlier report of heritability for males in rate of progression from regular drinking to AD generalizes to women and to other alcohol stage transitions. Findings also suggest the need to consider stage-specific environmental contributions to alcohol outcomes in developing interventions.
Alcohol Dependence; Genetics; Women; Transition; Course
Early-onset alcohol use is associated with increased vulnerability to subsequent alcohol abuse and dependence. However, not all early-onset alcohol users develop alcohol use disorders (AUDs). Using a sample of young women from the U.S., we identify correlates that contribute to a greater likelihood of AUDs in early-onset alcohol users.
Using interview and questionnaire data on participants of the Missouri Adolescent Female Twin Study (MOAFTS), we examine whether measures from domains including socio-demographic, pubertal development, religiosity, educational achievement, adverse life events, internalizing disorders, externalizing disorders and family history and discipline were associated with development of AUDs in 1,158 women who had their first drink of alcohol prior to age 16.
Early-onset drinkers were 3.6 times more likely to meet criteria for AUDs than later onset drinkers. While univariate analyses revealed that a host of correlates were associated with likelihood of AUDs in early-onset drinkers, multivariate analyses suggested that, even after accounting for a particularly early age of onset of drinking, those with a history of physical abuse, co-twin alcohol problems, conduct disorder, regular smoking, older peers and peer substance use were considerably more likely to meet criteria for AUDs than early onset drinkers without a lifetime history of these correlates.
The progression from first drink to AUDs is complex, and while early age at first drink is a potent risk factor, other aspects of psychopathology, family history, conduct problems and peer affiliations can exacerbate or alleviate the risk of AUDs in these young female drinkers.
alcohol; early-onset; alcohol abuse/dependence; female
The Hangover Symptoms Scale (HSS) assesses the frequency of 13 symptoms experienced after drinking in the past year. Cross-sectional analyses in college drinkers showed preliminary evidence for the validity of the HSS (Slutske et al., 2003). The current investigation extended this work by examining the construct validity of the HSS in an ecological momentary assessment investigation.
Frequent drinkers (N = 404) carried electronic diaries to track their daily experiences over three weeks. Each morning, the diary assessed prior-night drinking behaviors, the presence of current hangover, and intensity of current headache and nausea.
Adjusting for sex and body mass, the HSS significantly predicted diary endorsement of hangover (OR = 2.11, 95% CI = 1.78–2.49, p <.001). Participants who endorsed the HSS headache and nausea items were especially likely to report elevations of corresponding symptoms in diary records made the morning after drinking. HSS scores incrementally predicted hangover when the number of drinks consumed in the episode was covaried but did not moderate the relationship between the number of drinks and diary hangover reports.
The HSS appears to be a valid tool for hangover research. Higher HSS scores identify individuals who complain of “real world” hangovers and who may be especially likely to display particular symptoms after a night of drinking. Past hangovers predicted future hangovers, suggesting hangovers do not necessarily discourage or inhibit future drinking, at least across the several-week time interval studied here. There is a need to develop and evaluate complementary measures that can more directly index individual differences in hangover susceptibility in survey designs.
hangover; symptoms; questionnaire; Hangover Symptoms Scale; ecological momentary assessment
Gut microbial communities represent one source of human genetic and metabolic diversity. To examine how gut microbiomes differ between human populations when viewed from the perspective of component microbial lineages, encoded metabolic functions, stage of postnatal development, and environmental exposures, we characterized bacterial species present in fecal samples obtained from 531 individuals representing healthy Amerindians from the Amazonas of Venezuela, residents of rural Malawian communities, and inhabitants of USA metropolitan areas, as well as the gene content of 110 of their microbiomes. This cohort encompassed infants, children, teenagers and adults, parents and offspring, 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 representation of genes involved in vitamin biosynthesis and metabolism. Pronounced differences in bacterial species assemblages and functional gene repertoires were noted between individuals residing in the USA compared to the other two countries. These distinctive features are evident in early infancy as well as adulthood. In addition, the similarity of fecal microbiomes among family members extends across cultures. These findings underscore the need to consider the microbiome when evaluating human development, nutritional needs, physiological variations, and the impact of Westernization.
Earlier studies have found an elevated risk for psychopathology and suicidal behavior associated with childhood sexual abuse (CSA); however the degree to which risk is mediated by depression and post-traumatic stress disorder (PTSD) in women and men remains unclear. We examined these issues in data from a family study of childhood maltreatment (N=2559). We found significant CSA-associated risk for depression, PTSD, and suicidal behavior for women and men. In survival analyses controlling for these disorders, we observed persistent, but somewhat reduced, CSA-associated risk for suicidal ideation and suicide attempt. Our findings thus suggest these disorders partially mediate CSA-associated risk.
Genetic risk for alcohol dependence has been shown to overlap with genetic factors contributing to variation in dimensions of personality. Though drinking motives have been posited as important mediators of the alcohol-personality relation, the extent to which the genetic covariance between alcohol use disorder (AUD) symptoms (i.e. abuse and dependence criteria) and personality is explained by genetic factors contributing to variation in drinking motives remains unclear.
Using data from 2,904 young adult female twins, the phenotypic and genetic associations among personality dimensions (constraint [measured by the Multidimensional Personality Questionnaire; Tellegen, 1982], conscientiousness, neuroticism, and agreeableness [measured by the NEO-PI; Costa & McCrae, 1985]), internal drinking motives (enhancement and coping motives [measured by the Drinking Motive Questionnaire; Cooper, 1994]), and AUD symptoms were tested.
Significant genetic associations were found between all personality measures and AUD symptoms. Coping motives showed significant genetic overlap with AUD symptoms and most personality measures, whereas enhancement motives were not significantly heritable. Adjusting for coping motives, genetic correlations between AUD symptoms and traits of neuroticism and agreeableness were no longer statistically significant.
Findings suggest that genetic variation in drinking to cope might account for a considerable proportion of the genetic covariance between specific personality dimensions and AUD symptoms.
behavior genetics; personality; drinking motives; alcohol use disorders
Serum butyrylcholinesterase (BCHE) activity is associated with obesity, blood pressure and biomarkers of cardiovascular and diabetes risk. We have conducted a genome-wide association scan to discover genetic variants affecting BCHE activity, and to clarify whether the associations between BCHE activity and cardiometabolic risk factors are caused by variation in BCHE or whether BCHE variation is secondary to the metabolic abnormalities. We measured serum BCHE in adolescents and adults from three cohorts of Australian twin and family studies. The genotypes from ∼2.4 million single-nucleotide polymorphisms (SNPs) were available in 8791 participants with BCHE measurements. We detected significant associations with BCHE activity at three independent groups of SNPs at the BCHE locus (P = 5.8 × 10−262, 7.8 × 10−47, 2.9 × 10−12) and at four other loci: RNPEP (P = 9.4 × 10−16), RAPH1-ABI2 (P = 4.1 × 10−18), UGT1A1 (P = 4.0 × 10−8) and an intergenic region on chromosome 8 (P = 1.4 × 10−8). These loci affecting BCHE activity were not associated with metabolic risk factors. On the other hand, SNPs in genes previously associated with metabolic risk had effects on BCHE activity more often than can be explained by chance. In particular, SNPs within FTO and GCKR were associated with BCHE activity, but their effects were partly mediated by body mass index and triglycerides, respectively. We conclude that variation in BCHE activity is due to multiple variants across the spectrum from uncommon/large effect to common/small effect, and partly results from (rather than causes) metabolic abnormalities.
Many states require screening of individuals arrested for driving under the influence of alcohol (DUI) to determine recidivism risk and the need for treatment based on severity of alcohol problems. Several screening instruments use DSM-IV criteria for alcohol abuse and dependence to assess alcohol problems in this population, but whether they adequately measure alcohol problems in individuals with DUIs has not been examined. In addition, gender differences in DUI samples suggest that female offenders have more severe alcohol problems than male offenders. The current study examines differences in alcohol criteria functioning by DUI history and gender using an item response theory (IRT) approach.
Data from diagnostic interviews with 8605 participants in the Collaborative Study on the Genetics of Alcoholism, including 1655 who ever reported a DUI arrest (20% women), were used to examine differences in alcohol criteria functioning between men and women with and without DUIs. The factor underlying item response was conceptualized as unidimensional, representing alcohol problem severity.
Social/interpersonal problems, larger/longer, and inability/persistent desire to quit displayed greater discrimination of IRT-defined alcohol problem severity among individuals with DUIs than those without. Irrespective of DUI status, women had a higher threshold than men for time spent drinking or recovering. Women without DUIs had a higher threshold than similar men for social/interpersonal problems. Taken as a whole, the criteria yielded similar amounts of information in all groups.
DSM-IV criteria for alcohol abuse and dependence adequately detect alcohol problem severity in individuals with DUIs and some are better at detecting severity in this particularly high-risk group than in individuals without DUIs. However, the criteria as a whole are equally effective in measuring alcohol problem severity among individuals with and without DUIs, and may be used with confidence in screening DUI offenders.
DUI; Alcohol Use Disorder; Item Response Theory
To determine the prevalence of past 12 month DSM-5 alcohol use disorders (AUDs), to quantify and characterize individuals who remain stably unaffected or affected and those who diagnostically “switch” between DSM-IV and DSM-5 classifications.
Data from the nationally representative Wave 2 of the National Epidemiological Survey of Alcohol and Related Conditions (NESARC) collected in 2004–2005.
General population survey.
All surveyed participants (N=34,653, aged 21 and older) and 29,993 individuals reporting lifetime alcohol use across both waves of NESARC.
DSM-IV and DSM-5 criteria were coded using proposed guidelines.
The prevalence of DSM-5 AUDs was 10.8% with the corresponding prevalence of DSM-IV abuse/dependence being 9.7%, implying a modest 11.3% increase. Those who diagnostically switched from affected to unaffected (19.6% of DSM-IV affected) were most likely to have endorsed hazardous use, particularly due to drinking and driving while those who transitioned from unaffected to affected (3.3% of DSM-IV unaffected) were primarily DSM-IV diagnostic orphans reporting larger/longer and quit/cut-back. Dropping the legal criterion did not significantly affect the prevalence while the addition of craving also had a relatively modest impact on prevalence.
The proposed DSM-5 revisions successfully eliminate individuals previously diagnosed with DSM-IV alcohol abuse primarily due to hazardous use alone and incorporate diagnostic orphans into the diagnostic realm. Definitions of craving and importantly, hazardous use require considerable attention as it is likely that they will contribute to variations in reports of increased prevalence of AUDs between DSM-IV to DSM-5.
alcohol; Alcohol Use Disorders; DSM-5; NESARC
Human mate choice is central to individuals’ lives and to the evolution of the species, but the basis of variation in mate choice is not well understood. Here we look at a large community-based sample of twins and their partners and parents (N > 20,000 individuals) to test for genetic and family environmental influences on mate choice, with and without controlling for the effects of assortative mating. Key traits are analyzed, including height, body mass index, age, education, income, personality, social attitudes, and religiosity. This revealed near-zero genetic influences on male and female mate choice over all traits and no significant genetic influences on mate choice for any specific trait. A significant family environmental influence was found for the age and income of females’ mate choices, possibly reflecting parental influence over mating decisions. We also tested for evidence of sexual imprinting, where individuals acquire mate-choice criteria during development by using their opposite-sex parent as the template of a desirable mate; there was no such effect for any trait. The main discernable pattern to mate choice was assortative mating; we found that partner similarity was due to initial choice rather than convergence and also due at least in part to phenotypic matching.
mate choice; mate preferences; behaviour genetics; evolutionary psychology; sexual imprinting; assortative mating