Population-based Swedish Twin Registry Research Articles

Genetic and environmental aspects in the association between attention-deficit hyperactivity disorder symptoms and binge-eating behavior in adults: a twin study.

Prior research demonstrated that attention-deficit hyperactivity disorder (ADHD) is associated with binge-eating behavior, binge-eating disorder (BED), and bulimia nervosa (BN). The aim of this study was to investigate these associations in an adult twin population, and to determine the extent to which ADHD symptoms and binge-eating behavior share genetic and environmental factors. We used self-reports of current ADHD symptoms and lifetime binge-eating behavior and associated characteristics from a sample of over 18 000 adult twins aged 20-46 years, from the population-based Swedish Twin Registry. Mixed-effects logistic regression was used to examine the association between ADHD and lifetime binge-eating behavior, BED, and BN. Structural equation modeling was used in 13 773 female twins to determine the relative contribution of genetic and environmental factors to the association between ADHD symptoms and binge-eating behavior in female adult twins. ADHD symptoms were significantly associated with lifetime binge-eating behavior, BED, and BN. The heritability estimate for current ADHD symptoms was 0.42 [95% confidence interval (CI) 0.41-0.44], and for lifetime binge-eating behavior 0.65 (95% CI 0.54-0.74). The genetic correlation was estimated as 0.35 (95% CI 0.25-0.46) and the covariance between ADHD and binge-eating behavior was primarily explained by genetic factors (91%). Non-shared environmental factors explained the remaining part of the covariance. The association between adult ADHD symptoms and binge-eating behavior in females is largely explained by shared genetic risk factors.

Childhood maltreatment and attention deficit hyperactivity disorder symptoms in adults: a large twin study.

Childhood maltreatment (CM) has been associated with increased risk of attention deficit hyperactivity disorder (ADHD) in children and adults. It is, however, unclear whether this association is causal or due to familial confounding. Data from 18 168 adult twins, aged 20-46 years, were drawn from the population-based Swedish twin registry. Retrospective self-ratings of CM (emotional and physical neglect, physical and sexual abuse and witnessing family violence), and self-ratings for DSM-IV ADHD symptoms in adulthood were analysed. Possible familial confounding was investigated using a within twin-pair design based on monozygotic (MZ) and dizygotic (DZ) twins. CM was significantly associated with increased levels of ADHD symptom scores in adults [regression coefficient: 0.40 standard deviations, 95% confidence interval (CI) 0.37-0.43]. Within twin-pair analyses showed attenuated but significant estimates within DZ (0.29, 95% CI 0.21-0.36) and MZ (0.18, 95% CI 0.10-0.25) twin pairs. Similar results emerged for hyperactive/impulsive and inattentive ADHD symptom scores separately in association with CM. We conducted sensitivity analyses for early maltreatment, before age 7, and for abuse and neglect separately, and found similarly reduced estimates in DZ and MZ pairs. Re-traumatization after age 7 did not significantly influence results. CM was significantly associated with increased ADHD symptoms in adults. Associations were partly due to familial confounding, but also consistent with a causal interpretation. Our findings support cognitive neuroscience studies investigating neural pathways through which exposure to CM may influence ADHD. Clinicians treating adults with ADHD should be aware of the association with maltreatment.

DEMENTIA AFTER SURGERY IN SWEDEN

There is currently a controversy regarding the longterm impact of major surgery on subsequent cognitive performance and risk for dementia. A nested case-control study was performed within the population-based Swedish Twin Registry (STR) based on two samples of individuals: a clinical sample with individuals with a diagnosis of dementia based on clinical assessment within STR studies, and a register sample with dementia diagnosis retrieved from the Swedish National Patient Registry (NPR), Cause of death registry and Prescribed drug registry. All dementia cases were matched with 5 non-demented individuals and combined with information on hospitalizations and surgical procedures recorded in the NPR between 1977-2012. Hospitalizations for surgical or non-surgical conditions are associated with increased risk for dementia, however, hospitalizations for non-surgical reasons or critical illness are associated with a markedly higher risk for dementia than for surgical procedures. The risks of dementia increased with increasing number of non-surgical hospitalizations, and were significant 10 to 20 years past hospitalization. There was no increased risk with surgery after 80 years of age, which may reflect selection bias. Patients and providers should be more concerned about the consequences of repeated hospitalizations or critical illness than about surgery as a major risk factor for dementia.

Midlife Alcohol Consumption and Risk of Dementia Over 43 Years of Follow-Up: A Population-Based Study From the Swedish Twin Registry.

Midlife alcohol consumption (beer, wine, and spirits) was examined in relation to dementia incidence over 43 years. Participants were 12,326 members of the population-based Swedish Twin Registry born during 1907-1925 who responded to items about alcohol consumption in 1967/1970, subsequently classified as nondrinking (0 grams of ethanol per day), light (1-5g/d), moderate (5-12g/d), heavy (12-24g/d), and very heavy (>24g/d) drinking. Dementia was identified from the National Patient and Cause of Death Registries. Cox proportional hazard models adjusted for cluster-correlated data were used in cohort analyses. Conditional logistic regression (dementia-discordant pairs) and mixed effects models (dementia-concordant pairs) were used in twin analyses. Overall, nondrinkers did not differ from light drinkers in dementia risk. Heavy drinking (hazard ratio = 1.10, p = .028) and very heavy drinking (hazard ratio = 1.18, p = .033) were associated with increased dementia risk controlling for sociodemographic, lifestyle, and cardiovascular factors. More alcohol from spirits was related to increased risk of dementia, whereas more alcohol from wine with decreased risk, although the association for wine reversed direction at high amounts. Relative to co-twins drinking light amounts, moderate-to-heavy drinking twins had (a) greater risk of dementia by 57% (p = .006, 300% in monozygotic pairs only) and (b) reduced time to dementia by 4.76 years (p = .019, 4.78 years in monozygotic pairs only). Averaging more than 12 grams of alcohol per day may increase risk of dementia. Alcohol from spirits appears particularly important for the increased dementia risk. Genetic and/or familial factors do not explain these associations. Alcohol use reduction may be a useful population-wide intervention strategy.

Alcohol consumption at midlife and risk of stroke during 43 years of follow-up: cohort and twin analyses.

Although alcohol-stroke association is well known, the age-varying effect of alcohol drinking at midlife on subsequent stroke risk across older adulthood has not been examined. The effect of genetic/early-life factors is also unknown. We used cohort and twin analyses of data with 43 years of follow-up for stroke incidence to help address these gaps. All 11 644 members of the population-based Swedish Twin Registry born 1886 to 1925 with alcohol data aged ≤60 years were included. The interaction of midlife alcohol consumption by age at stroke was evaluated in Cox-regression and analyses of monozygotic twins were used. Covariates were baseline age, sex, cardiovascular diseases, diabetes mellitus, stress reactivity, depression, body mass index, smoking, and exercise. Altogether 29% participants developed stroke. Compared with very-light drinkers (<0.5 drink/d), heavy drinkers (>2 drinks/d) had greater risk of stroke (hazard ratio, 1.34; P=0.02) and the effect for nondrinkers approached significance (hazard ratio, 1.11; P=0.08). Age increased stroke risk for nondrinkers (P=0.012) and decreased it for heavy drinkers (P=0.040). Midlife heavy drinkers were at high risk from baseline until the age of 75 years when hypertension and diabetes mellitus grew to being the more relevant risk factors. In analyses of monozygotic twin-pairs, heavy drinking shortened time to stroke by 5 years (P=0.04). Stroke-risk associated with heavy drinking (>2 drinks/d) in midlife seems to predominate over well-known risk factors, hypertension and diabetes, until the age of ≈75 years and may shorten time to stroke by 5 years above and beyond covariates and genetic/early-life factors. Alcohol consumption should be considered an age-varying risk factor for stroke.

The heritability of clinically diagnosed attention deficit hyperactivity disorder across the lifespan

No prior twin study has explored the heritability of clinically diagnosed attention deficit hyperactivity disorder (ADHD). Such studies are needed to resolve conflicting results regarding the importance of genetic effects for ADHD in adults. We aimed to estimate the relative contribution of genetic and environmental influences for clinically diagnosed ADHD across the lifespan with a specific focus on ADHD in adults. Information on zygosity and sex was obtained from 59514 twins born between 1959 and 2001 included in the nationwide population-based Swedish Twin Registry. Clinical data for ADHD diagnoses (i.e. stimulant or non-stimulant medication for ADHD) were obtained from the Swedish Prescribed Drug Register (PDR) and from the National Patient Register (i.e. ICD-10 diagnosis of ADHD). Twin methods were applied to clinical data of ADHD diagnoses using structural equation modeling with monozygotic (MZ) and dizygotic (DZ) twins. The best-fitting model revealed a high heritability of ADHD [0.88, 95% confidence interval (CI) 0.83-0.92] for the entire sample. However, shared environmental effects were non-significant and of minimal importance. The heritability of ADHD in adults was also substantial (0.72, 95% CI 0.56-0.84). This study shows that the heritability of clinically diagnosed ADHD is high across the lifespan. Our finding of high heritability for clinically diagnosed ADHD in adults indicates that the previous reports of low heritability are best explained by rater effects, and that gene-identification studies of ADHD in adults need to consider pervasiveness (e.g. multiple raters) and developmentally (e.g. childhood-onset criteria) informative data.

Reexamining the Association Between Fertility and Longevity: Testing the Disposable Soma Theory in a Modern Human Sample of Twins

The disposable soma theory proposes a trade-off between fertility and longevity but existing findings on this association have been mixed. This study used data from 15,622 twins born between 1901 and 1925 ascertained from the population-based Swedish Twin Registry to test the child-longevity association and whether it is accounted for by individual-level factors or by genetic and environmental factors shared by family members. Based on survival analysis, both women and men with children had significantly longer survival relative to the childless, with a slightly higher relative advantage in men. Adjustments for demographic factors and cotwin fertility did not mediate the parenting-survival association, indicating that this association is attributable to individual-level factors associated with fertility rather than family-level environmental or genetic factors shared by cotwins. These results, derived from a large, population-based sample, are inconsistent with the disposable soma theory as applied to modern human populations.

Occupational exposure in Parkinsonian disorders: A 43-year prospective cohort study in men

BackgroundSeveral occupations and occupational exposures have been investigated for associations with Parkinson’s disease. Common findings are increased risk associated with pesticide exposure and no association between Parkinson’s disease and welding. MethodsWe explored the association between a broad range of possible occupational risk factors and Parkinson’s disease as well as Parkinson’s disease plus other forms of Parkinsonism (referred to as Parkinsonian disorders), using prospectively collected data in the population-based Swedish Twin Registry. A cohort of 14,169 Swedish men was followed for up to 43 years. We identified 234 Parkinsonian disorder cases including 204 Parkinson’s disease cases with complete data. We assessed exposure to 14 chemical and biological compounds through a job exposure matrix. Hazard ratios (HR) with 95% confidence intervals (CI) adjusted for age, smoking, and education were used to estimate the relative risk of disease associated with exposure. ResultsExposure to inorganic dust was associated with increased risk of Parkinson’s disease and Parkinsonian disorders, HR 1.6 (95% CI 1.1–2.4) and 1.5 (1.0–2.2) respectively. There was no association between Parkinson’s disease or Parkinsonian disorders and occupational exposure to pesticides, welding smoke, metal dust, wood dust, animal handling, stone and concrete dust, chrome and nickel dust, quartz dust, organic dust, oil, asbestos, organic solvents and irritating gas. ConclusionsInorganic dust should be explored further as a potential risk factor for Parkinson’s disease. Occupational exposure to pesticides and twelve other compounds explored in this study may not be associated with risk of Parkinson’s disease in Swedish men.

Personality traits in attempted and completed suicide

ObjectiveThough widely used in clinical and biological studies, no investigation of the factor structure of the Karolinska Scales of Personality (KSP) has been performed in suicide attempters. There are very few studies of personality traits in suicide completers. The aim of the present study was to assess the factor structure of KSP in suicide attempters. A secondary aim was to examine whether the factor structure of the KSP was related to gender and/or to violent method of the suicide attempt or to suicide completion. MethodThe factor structure of the KSP was analysed in data from 165 suicide attempters from the Suicide Prevention Clinic at the Karolinska University Hospital using principal component analysis and orthogonal varimax rotation for the factor extraction. The effect of gender and (1) used method in the suicide attempt (violent versus nonviolent), and (2) later completed suicide on the factors was assessed in two separate series of the two-way ANOVAs. ResultA four-factor solution appeared: (1) Neuroticism, (2) Nonconformity, (3) Psychoticism and (4) Extraversion. Men who later completed suicide reported more Extroversion than male survivors. ConclusionThe obtained factor structure is comparable to a previous factor structure in a group of twins from the population-based Swedish Twin Registry indicating that no specific personality structure characterized the current sample. Differences in personality traits between suicide completers and survivors indicate that these groups may have some distinct characteristics.

Heritability of Parkinson disease in Swedish twins: a longitudinal study

Previous twin studies report no heritability of Parkinson's disease (PD) based on cross sectional information. Here, we apply a longitudinal design and re-evaluate cross sectional data in the population-based Swedish Twin Registry (STR) using clinical as well as hospital discharge and cause of death diagnoses. In the longitudinal analyses (based on 46,436 individuals), we identified 542 twins with PD and 65 twins with Parkinsonism. Concordance rates for PD were 11% for monozygotic and 4% for same-sexed dizygotic twin pairs, with a heritability estimate of 34%. Concordance rates for PD or parkinsonism were 13% for monozygotic and 5% for same-sexed dizygotic twin pairs, with a heritability estimate of 40%. In the cross sectional analyses (based on 49,814 individuals), we identified 287 twins with PD and 79 twins with parkinsonism. Concordance rates for PD were 4% for monozygotic and same-sexed dizygotic twin pairs and 0 for opposite-sexed twin pairs. Concordance rates for PD or parkinsonism were somewhat higher but the heritability estimate was nonsignificant. Our longitudinal analyses demonstrate that PD and parkinsonism are modestly heritable.

The Genetic and Environmental Etiology of Antisocial Behavior from Childhood to Emerging Adulthood

Previous research suggests that both genetic and environmental influences are important for antisocial behavior across the life span, even though the prevalence and incidence of antisocial behavior varies considerably across ages. However, little is known of how genetic and environmental effects influence the development of antisocial behavior. A total of 2,600male and female twins from the population-based Swedish Twin Registry were included in the present study. Antisocial behavior was measured on four occasions, when twins were 8-9, 13-14, 16-17, and 19-20years old. Longitudinal analyses of the data were conducted using structural equation modeling. The stability of antisocial behavior over time was explained by a common latent persistent antisocial behavior factor. A common genetic influence accounted for 67% of the total variance in this latent factor, the shared environment explained 26%, and the remaining 7% was due to the non-shared environment. Significant age-specific shared environmental factors were found at ages 13-14years, suggesting that common experiences (e.g., peers) are important for antisocial behavior at this age. Results from this study show that genetic as well as shared environmental influences are important in antisocial behavior that persists from childhood to emerging adulthood.

Genetic influences on suicide and nonfatal suicidal behavior: Twin study findings

It has been well established that suicidal behavior is familial. Twin studies provide a unique opportunity to distinguish genetic effects from other familial influences. Consistent with findings from previous twin studies, including case series and selected samples, data from the population-based Swedish Twin Registry clearly demonstrate the importance of genetic influences on suicide. Twin studies of suicidal ideation and suicide attempts also implicate genetic influences, even when accounting for the effects of psychopathology. Future work is needed to evaluate the possibility of age and gender differences in heritability of suicide and nonfatal suicidal behavior.

A population-based twin study of the genetic and environmental relationship of major depression, regular tobacco use and nicotine dependence

Numerous epidemiological studies have reported a positive association between major depression (MD) and regular tobacco use (RU) or nicotine dependence (ND). However, few have used a genetically informative design to assess whether these traits share a common genetic and/or environmental liability. We assessed MD, RU and ND in same-sex twins from the population-based Swedish Twin Registry. In males, we examined both cigarette use and snus (smokeless tobacco) use. We used structural equation modeling to examine the relationship between MD, RU, and ND given RU. The results suggest modest correlations between MD and RU, and between MD and ND. In males, the liability shared between MD and RU is solely genetic for both cigarettes and snus, while MD and ND share both genetic and unique environmental influences. The continuation to ND given RU differed considerably between cigarette and snus users. In females, both MD-RU and MD-ND relationships are partially attributable to genetic and unique environmental correlations. The relationship among MD, RU and ND is at least partially attributable to shared genetic and environmental risk factors. The genetic and environmental correlations between traits are modest. The nature of the shared liability differs by sex, and in males, by the type of tobacco product used. Differences between previous reports and results presented in the current study are suggestive of population differences in how MD and tobacco use inter-relate.

Psychiatric morbidity associated with same-sex sexual behaviour: influence of minority stress and familial factors

Increased psychiatric morbidity has been widely reported among non-heterosexual individuals (defined as reporting a homosexual/bisexual identity and/or same-sex sexual partners). However, the causes of this psychiatric ill-health are mostly unknown. We attempted to estimate the influence of minority stress and familial factors on psychiatric disorder among adults with same-sex sexual partners. Self-report data from a 2005 survey of adults (age 20-47 years, n=17,379) in the population-based Swedish Twin Registry were analysed with regression modelling and co-twin control methodology. Rates of depression, generalized anxiety disorder (GAD), eating disorders, alcohol dependence and attention deficit hyperactivity disorder (ADHD) were increased among men and women with same-sex sexual experiences. Adjusting for perceived discrimination and hate crime victimization lowered this risk whereas controlling for familial (genetic or environmental) factors in within-twin pair comparisons further reduced or eliminated it. Components of minority stress influence the risk of psychiatric ill-health among individuals with any same-sex sexual partner. However, substantial confounding by familial factors suggests a common genetic and/or environmental liability for same-sex sexual behaviour and psychiatric morbidity.

Asthma, Eczema, Rhinitis and the Risk for Dementia

Background: Inflammation is associated with Alzheimer’s disease (AD) and dementia. In light of the chronic inflammatory properties of the atopic disorders asthma, eczema and rhinitis, we hypothesized an association with dementia. Methods: Self-reported asthma, eczema or rhinitis was assessed (prior to dementia follow-up) through questionnaires in the 1960s or 1970s in twins from the population-based Swedish Twin Registry. Dementia was assessed both longitudinally (n = 22,188), through linkages to two population-based registers, and cross-sectionally (n = 7,800), through telephone cognitive screening followed by a clinical evaluation of suspects of dementia. Risk ratios were estimated with Cox and logistic regression models controlling for vascular disease and genetic confounding. Results: In the longitudinal study, a history of atopy was positively associated with dementia (HR = 1.16; 1.01–1.33). In the cross-sectional study we found overall lower risks, none of which was statistically significant. Asthma was associated with a shorter survival time following AD onset. Conclusions: Atopy is associated with a modestly increased risk of AD and dementia that is not mediated by vascular disease or due to genetic confounding. A history of asthma is associated with shorter life expectancy after AD diagnosis.

Snus use and other correlates of smoking cessation in the Swedish Twin Registry.

We investigated 12 variables and their interactions as correlates of smoking cessation among regular smokers in the population-based Swedish Twin Registry (STR). Detailed information on tobacco use and personal characteristics were available from 14 715 male and female twins aged 42-64 years who participated in a screening of the population-based STR and reported being regular smokers in their lifetime. A two-stage analytic design was used to examine correlates of smoking cessation. The sample was split at random and significant main effects and interactions identified in the testing set were examined in the validation set. Hazard ratios (HRs) and 95% confidence intervals (CIs) describe the association between correlates and smoking cessation. Twelve main effects were significantly associated with smoking cessation in the testing set; eight were confirmed in the validation set. Of the nine interactions identified in the testing set, none remained significant when evaluated in the validation set after Bonferroni correction. HRs were highest for Swedish oral smokeless tobacco (snus) use (HR 2.70, 95% CI 2.30-3.20), >11 years of education (HR 1.57, 95% CI 1.43-1.73) and being married or cohabitating (HR 1.51, 95% CI 1.39-1.63). Although not statistically significant after Bonferroni correction, snus use also appeared important in the context of interactions, where lower nicotine dependence score, higher socio-economic status (SES) and greater body size were associated with smoking cessation only among participants who never used snus. Snus use was the strongest independent correlate of smoking cessation. Further studies should investigate the mechanism of this association.

Heritability of ultimatum game responder behavior

Experimental evidence suggests that many people are willing to deviate from materially maximizing strategies to punish unfair behavior. Even though little is known about the origins of such fairness preferences, it has been suggested that they have deep evolutionary roots and that they are crucial for maintaining and understanding cooperation among non-kin. Here we report the results of an ultimatum game, played for real monetary stakes, using twins recruited from the population-based Swedish Twin Registry as our subject pool. Employing standard structural equation modeling techniques, we estimate that >40% of the variation in subjects' rejection behavior is explained by additive genetic effects. Our estimates also suggest a very modest role for common environment as a source of phenotypic variation. Based on these findings, we argue that any attempt to explain observed ultimatum bargaining game behavior that ignores this genetic influence is incomplete.

Irritable Bowel Syndrome: A Co-Twin Control Analysis

Among individuals who satisfy diagnostic criteria for both major depressive disorder (MDD) and irritable bowel syndrome (IBS), little is known about the role of familial tendency and environmental influences in disease susceptibility. Therefore, we aimed to examine if there is a genetic component to the co-occurrence of MDD and IBS in participants from the population-based Swedish Twin Registry. We implemented a nested case-control analysis and a co-twin control analysis. IBS cases were ascertained using an adapted version of the Rome II criteria and MDD cases were assessed using a shortened version of the Computerized International Diagnostic Interview. The case-control analysis included individuals with complete covariate information (N = 29,616), and adjusted for twin pair, 3-yr age band, and sex. The co-twin control analysis considered 288 twin pairs discordant for IBS. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using generalized estimating equations for the case-control analysis and conditional logistic regression for the co-twin control analysis. In all analyses, comorbid disorders of chronic widespread pain, chronic fatigue-like illness, and MDD were more common in IBS cases than controls. In the case-control analysis, individuals with IBS had an increased odds of MDD (OR 2.7, 95% CI 2.3-3.2). In the co-twin analysis, the association was similar (OR 2.2, 95% CI 1.5-3.3) when both MZ and DZ twins were used, and larger among only MZ twins (OR 3.2, 95% CI 1.7-6.1). From this analysis, we found no evidence that genetic and family environmental factors explain the association between MDD and IBS. Rather, one of these disorders appears to be part of the disease-causing sequence of events, or biologic disease pathway, for the other disorder. However, it was not possible to evaluate the timing of onset between MDD and IBS in this study.

Do Work-related Stress and Reactivity to Stress Predict Dementia More Than 30 Years Later?

The purpose of this study was to examine associations for work-related stress, reactivity to stress, and subsequent risk of dementia. The sample consisted of members of the population-based Swedish Twin Registry who were participants in the HARMONY study (n=2,049). We used case control and cotwin control designs, with information on work-related stress and reactivity to stress collected as part of a questionnaire completed in 1967. Dementia was diagnosed approximately 30 years later using a 2-stage procedure-screening for cognitive impairment followed by full clinical evaluation. We found that measures of work-related stress (job dissatisfaction and high job demands) were not associated with dementia risk. Greater reactivity to stress predicted higher risk of dementia controlling for age, education, sex, occupational status, alcohol use, and smoking status (odds ratio=1.57, 95% confidence interval 1.08-2.31). Cotwin control analyses also showed that dementia probands were more likely to report high reactivity to stress than their nondemented cotwins. We did not find evidence of an interaction between work stress and reactivity in predicting dementia. Overall, indicators of stress due to environment (ie, work) were not associated with dementia, whereas the individual characteristic of reactivity to stress predicted dementia risk.

The sources of co-morbidity between major depression and generalized anxiety disorder in a Swedish national twin sample

Prior studies report high levels of co-morbidity between major depression (MD) and generalized anxiety disorder (GAD) and suggest that these disorders are closely related genetically. The personality trait of neuroticism (N) is substantially correlated with risk for MD and GAD. Bivariate twin models were applied to lifetime diagnoses of modified DSM-IV diagnosis of MD and GAD obtained at personal interview in 1998-2003 with 37296 twins from the population-based Swedish Twin Registry. A trivariate Cholesky model with N, MD and GAD was applied to a subset (23280 members of same-sex twin pairs) who completed a self-report questionnaire assessing N in 1972-1973. In the best-fit bivariate model, the genetic correlation between MD and GAD was estimated at +1.00 in females and +0.74 in males. Individual-specific environmental factors were also shared between the two disorders with an estimated correlation of +0.59 in males and +0.36 in females. In the best-fit trivariate Cholesky model, genetic factors indexed by N impacted equally on risk for MD and GAD in males and females. However, in both sexes, genetic risk factors indexed by N contributed only around 25% to the genetic correlation between MD and GAD. Genetic risk factors for lifetime MD and GAD are strongly correlated, with higher correlations in women than in men. Although genetic risk factors indexed by the personality trait of N contribute substantially to risk for both MD and GAD, the majority of genetic covariance between the two disorders results from factors not shared with N.