Shared genetic risk between anorexia nervosa and cardiovascular disease events: Evidence from genome-wide association studies.

OBJECTIVE: Cardiovascular complications occur in up to 80% of patients with anorexia nervosa (AN), yet the underlying mechanisms warrant further investigation. We assessed the genetic correlation (rg ) between AN and cardiovascular disease (CVD) events to inform whether elevated cardiovascular risk among individuals with AN is due to shared genetic effects. METHOD: We used genome-wide association study summary statistics for AN (N = 72,517), AN with binge eating (N = 12,630), AN without binge eating (N = 12,516), and six CVD events (N = 390,142 to 977,323). We calculated the rg s via linkage disequilibrium score regression and corrected for multiple testing using false discovery rate. RESULTS: Significant rg s emerged between AN with heart failure (rg  = -0.11, SE = 0.05, q = .04) and myocardial infarction (rg  = -0.10, SE = 0.03, q = .01). AN with binge eating had a significant rg with myocardial infarction (rg  = -0.15, SE = 0.06, q = .02). No significant rg emerged between AN without binge eating and any CVD event. DISCUSSION: Some loci affect the liability to AN and CVD in opposite directions and the shared genetic effects may not be consistent across all CVD events. Our results provide further evidence suggesting that the elevated cardiovascular risk in AN may not be due to shared genetic underpinnings, but more likely a downstream consequence of the disease.

Differential genetic associations between dimensions of eating disorders and alcohol involvement in late adolescent twins.

BACKGROUND: Twin studies have demonstrated shared genetic and environmental effects between eating disorders and alcohol involvement in adults and middle adolescents. However, fewer studies have focused on late adolescents or investigated a wide range of eating disorder dimensions and alcohol involvement subscales in both sexes. We examined genetic and environmental correlations among three eating disorder dimensions and two alcohol involvement subscale scores in late adolescent twins using bivariate twin models. METHODS: Participants were 3568 female and 2526 male same-sex twins aged 18 years old from the Child and Adolescent Twin Study in Sweden. The Eating Disorder Inventory-2 (EDI) assessed the drive for thinness, bulimia, and body dissatisfaction. Alcohol involvement was assessed with the Alcohol Use Disorder Identification Test consumption (AUDIT-C) and problem (AUDIT-P) subscales. RESULTS: Only phenotypic and twin correlations in female twins met our threshold for twin modeling. The proportion of total variance for each trait accounted for by additive genetic factors ranged from 0.50 to 0.64 in female twins, with the rest explained by nonshared environmental factors and measurement error. Shared environmental factors played a minimal role in the variance of each trait. The strongest genetic correlation (ra ) emerged between EDI bulimia and AUDIT-P (ra = 0.46, 95% confidence interval: 0.37, 0.55), indicating that the proportion of genetic variance of one trait that was shared with the other trait was 0.21. Nonshared environmental correlations between eating disorder dimensions and alcohol involvement ranged from 0.03 to 0.13. CONCLUSIONS: We observed distinct patterns of genetic and environmental effects for co-occurring eating disorder dimensions and alcohol involvement in female vs. male twins, supporting sex-specific treatment strategies for late adolescents with comorbid eating disorders and alcohol use disorder. Our findings emphasize the importance of assessing family history of multiple eating disorder dimensions while treating late adolescents with problematic alcohol use, and vice versa, to improve detection and treatment.

ARFID Genes and Environment (ARFID-GEN): study protocol.

BACKGROUND: The Avoidant Restrictive Food Intake Disorder - Genes and Environment (ARFID-GEN) study is a study of genetic and environmental factors that contribute to risk for developing ARFID in children and adults. METHODS: A total of 3,000 children and adults with ARFID from the United States will be included. Parents/guardians and their children with ARFID (ages 7 to 17) and adults with ARFID (ages 18 +) will complete comprehensive online consent, parent verification of child assent (when applicable), and phenotyping. Enrolled participants with ARFID will submit a saliva sample for genotyping. A genome-wide association study of ARFID will be conducted. DISCUSSION: ARFID-GEN, a large-scale genetic study of ARFID, is designed to rapidly advance the study of the genetics of eating disorders. We will explicate the genetic architecture of ARFID relative to other eating disorders and to other psychiatric, neurodevelopmental, and metabolic disorders and traits. Our goal is for ARFID to deliver "actionable" findings that can be transformed into clinically meaningful insights. TRIAL REGISTRATION: ARFID-GEN is a registered clinical trial: clinicaltrials.gov NCT05605067.

Arfid Genes and Environment (ARFID-GEN): Study Protocol.

Background: The Avoidant Restrictive Food Intake Disorder Genes and Environment (ARFID-GEN) study is a study of genetic and environmental factors that contribute to risk for developing ARFID in children and adults. Methods: A total of 3,000 children and adults with ARFID from the United States will be included. Parents/guardians and their children with ARFID (ages 7 to 17) and adults with ARFID (ages 18+) will complete comprehensive online consent, parent verification of child assent (when applicable), and phenotyping. Enrolled participants with ARFID will submit a saliva sample for genotyping. A genome-wide association study of ARFID will be conducted. Discussion: ARFID-GEN, a large-scale genetic study of ARFID, is designed to rapidly advance the study of the genetics of eating disorders. We will explicate the genetic architecture of ARFID relative to other eating disorders and to other psychiatric, neurodevelopmental, and metabolic disorders and traits. Our goal is for ARFID to deliver "actionable" findings that can be transformed into clinically meaningful insights. Trial registration: ARFID-GEN is a registered clinical trial: clinicaltrials.gov NCT05605067.

Food-restricted alcohol consumption: relation to psychopathology in college students.

Objective: Food-restricted alcohol consumption (FRAC) is a growing concern among college students. We investigated demographic and lifestyle characteristics and psychiatric symptoms associated with FRAC. Participants: College students (n = 561) at a large southeastern university in the United States. Methods: Participants completed online self-reported questionnaires assessing past-year FRAC, demographic and lifestyle characteristics, and psychiatric symptoms. Results: The past-year prevalence of FRAC was 23.89%. In the bivariate analyses, students engaging in FRAC had higher mean scores of multiple psychiatric symptoms, reported more harmful or hazardous drinking and suicidality, and were more likely to report a history of an eating disorder than their peers without FRAC. In a hierarchical regression model, binge eating, cognitive restraint, self-reported history of an eating disorder, and harmful or hazardous drinking were significantly associated with FRAC (ps < 0.05) after other psychiatric symptoms were included in the model. Conclusion: Our findings stress the importance of heightened awareness of FRAC in college.

Development and Validation of an Eating-Related Eco-Concern Questionnaire.

Eco-concern, the distress experienced relating to climate change, is associated with mental health, yet no study has examined disordered eating related to eco-concern. This study developed and validated a 10-item scale assessing Eating-Related Eco-Concern (EREC). Participants (n = 224) completed the EREC, Climate Change Worry Scale (CCWS), and Eating Disorder Examination-Questionnaire (EDE-Q). Construct validity, convergent validity, and internal consistency were evaluated. Sex differences in EREC were evaluated using t-tests. Associations among the EREC, CCWS, and EDE-Q were evaluated using linear regression models. Sensitivity analyses were conducted in individuals below EDE-Q global score clinical cut-offs. Factor analysis suggested that all items loaded adequately onto one factor. Pearson's correlation and Bland-Altman analyses suggested strong correlation and acceptable agreement between the EREC and CCWS (r = 0.57), but weak correlation and low agreement with the EDE-Q global score (r = 0.14). The EREC had acceptable internal consistency (α = 0.88). No sex difference was observed in the EREC in the full sample; females had a significantly higher mean score than males in sensitivity analysis. The EREC was significantly positively associated with the CCWS and EDE-Q global and shape concern scores, but not in sensitivity analysis. The EREC is a brief, validated scale that can be useful to screen for eating-related eco-concern.

Associations between eating disorder symptoms and smoking and vaping use and motives in college students.

A positive association between eating disorder (ED) symptoms and cigarette use exists. However, little is known about the association between ED symptoms and e-cigarette use, as well as how these symptoms are related to motives for using cigarettes and e-cigarettes. In this study, 716 college students (M age = 19.23, SD = 1.65; 61 % female) completed an online survey that included the Eating Pathology Symptoms Inventory, smoking and vaping questionnaires, and the Drinking Motives Questionnaire-Revised, which was modified for smoking and vaping. We examined mean differences in ED symptoms in lifetime (and past-month) cigarette and e-cigarette users versus non-users, and investigated correlations between ED symptoms and smoking and vaping motives. Finally, we evaluated whether biological sex influenced the results. Overall, 30.4 % of students reported lifetime smoking, 10.5 % reported past-month smoking, 23 % reported lifetime vaping, and 9.5 % reported past-month vaping. With the exception of higher mean scores for negative attitudes toward obesity in students reporting lifetime smoking versus never smoking after adjusting for sex (M = 5.97 vs. M = 4.52, t[713] = -3.76, q = 0.004), no significant mean differences emerged between those who used nicotine and those who did not, which reflected small to moderate effect sizes. Few associations were observed between ED symptoms and nicotine use motives. These findings suggest that the comorbidity between ED symptoms and smoking and vaping in a non-clinical sample is minimal, although additional research with larger sample sizes of males and females is needed.

Shared Genetic Factors Contributing to the Overlap between Attention-Deficit/Hyperactivity Disorder Symptoms and Overweight/Obesity in Swedish Adolescent Girls and Boys.

Attention-deficit/hyperactivity disorder (ADHD) and obesity are positively associated, with increasing evidence that they share genetic risk factors. Our aim was to examine whether these findings apply to both types of ADHD symptoms for female and male adolescents. We used data from 791 girl and 735 boy twins ages 16-17 years to examine sex-specific phenotypic correlations between the presence of ADHD symptoms and overweight/obese status. For correlations exceeding .20, we then fit bivariate twin models to estimate the genetic and environmental correlations between the presence of ADHD symptoms and overweight/obese status. ADHD symptoms and height/weight were parent- and self-reported, respectively. Phenotypic correlations were .30 (girls) and .08 (boys) for inattention and overweight/obese status and .23 (girls) and .14 (boys) for hyperactivity/impulsivity and overweight/obese status. In girls, both types of ADHD symptoms and overweight/obese status were highly heritable, with unique environmental effects comprising the remaining variance. Furthermore, shared genetic effects explained most of the phenotypic correlations in girls. Results suggest that the positive association of both types of ADHD symptoms with obesity may be stronger in girls than boys. Further, in girls, these associations may stem primarily from shared genetic factors.

Selective Inhibition of PDE4B Reduces Binge Drinking in Two C57BL/6 Substrains.

Cyclic AMP (cAMP)-dependent signaling is highly implicated in the pathophysiology of alcohol use disorder (AUD), with evidence supporting the efficacy of inhibiting the cAMP hydrolyzing enzyme phosphodiesterase 4 (PDE4) as a therapeutic strategy for drinking reduction. Off-target emetic effects associated with non-selective PDE4 inhibitors has prompted the development of selective PDE4 isozyme inhibitors for treating neuropsychiatric conditions. Herein, we examined the effect of a selective PDE4B inhibitor A33 (0-1.0 mg/kg) on alcohol drinking in both female and male mice from two genetically distinct C57BL/6 substrains. Under two different binge-drinking procedures, A33 pretreatment reduced alcohol intake in male and female mice of both substrains. In both drinking studies, there was no evidence for carry-over effects the next day; however, we did observe some sign of tolerance to A33's effect on alcohol intake upon repeated, intermittent, treatment (5 injections of 1.0 mg/kg, every other day). Pretreatment with 1.0 mg/kg of A33 augmented sucrose intake by C57BL/6NJ, but not C57BL/6J, mice. In mice with a prior history of A33 pretreatment during alcohol-drinking, A33 (1.0 mg/kg) did not alter spontaneous locomotor activity or basal motor coordination, nor did it alter alcohol's effects on motor activity, coordination or sedation. In a distinct cohort of alcohol-naïve mice, acute pretreatment with 1.0 mg/kg of A33 did not alter motor performance on a rotarod and reduced sensitivity to the acute intoxicating effects of alcohol. These data provide the first evidence that selective PDE4B inhibition is an effective strategy for reducing excessive alcohol intake in murine models of binge drinking, with minimal off-target effects. Despite reducing sensitivity to acute alcohol intoxication, PDE4B inhibition reduces binge alcohol drinking, without influencing behavioral sensitivity to alcohol in alcohol-experienced mice. Furthermore, A33 is equally effective in males and females and exerts a quantitatively similar reduction in alcohol intake in mice with a genetic predisposition for high versus moderate alcohol preference. Such findings further support the safety and potential clinical utility of targeting PDE4 for treating AUD.

Shared genetic risk between eating disorder- and substance-use-related phenotypes: Evidence from genome-wide association studies.

Eating disorders and substance use disorders frequently co-occur. Twin studies reveal shared genetic variance between liabilities to eating disorders and substance use, with the strongest associations between symptoms of bulimia nervosa and problem alcohol use (genetic correlation [rg ], twin-based = 0.23-0.53). We estimated the genetic correlation between eating disorder and substance use and disorder phenotypes using data from genome-wide association studies (GWAS). Four eating disorder phenotypes (anorexia nervosa [AN], AN with binge eating, AN without binge eating, and a bulimia nervosa factor score), and eight substance-use-related phenotypes (drinks per week, alcohol use disorder [AUD], smoking initiation, current smoking, cigarettes per day, nicotine dependence, cannabis initiation, and cannabis use disorder) from eight studies were included. Significant genetic correlations were adjusted for variants associated with major depressive disorder and schizophrenia. Total study sample sizes per phenotype ranged from ~2400 to ~537 000 individuals. We used linkage disequilibrium score regression to calculate single nucleotide polymorphism-based genetic correlations between eating disorder- and substance-use-related phenotypes. Significant positive genetic associations emerged between AUD and AN (rg = 0.18; false discovery rate q = 0.0006), cannabis initiation and AN (rg = 0.23; q < 0.0001), and cannabis initiation and AN with binge eating (rg = 0.27; q = 0.0016). Conversely, significant negative genetic correlations were observed between three nondiagnostic smoking phenotypes (smoking initiation, current smoking, and cigarettes per day) and AN without binge eating (rgs = -0.19 to -0.23; qs < 0.04). The genetic correlation between AUD and AN was no longer significant after co-varying for major depressive disorder loci. The patterns of association between eating disorder- and substance-use-related phenotypes highlights the potentially complex and substance-specific relationships among these behaviors.

Eating disorder symptoms in Asian American college students.

Inconsistent information on levels of eating pathology in Asian Americans exist. We investigated whether there were differences in mean scores for eating disorder (ED) symptoms among Whites, Asian Americans, and individuals identifying as another race (i.e., non-Asian people of color [NAPOC]). Participants included 716 college students (M age = 19.23; SD = 1.65) from a southeastern university. ED symptoms were assessed with the Eating Pathology Symptom Inventory (EPSI). Internalizing symptoms were evaluated via the Depression Anxiety and Stress Scale (DASS). One-way ANOVAs investigated mean differences in symptoms between racial groups, with and without adjusting for sex, BMI, and internalizing symptoms. Overall, 16% (n = 114) of the sample identified as Asian American, 67% (n = 477) as White, and 17% (n = 125) as NAPOC. After correcting for multiple testing and adjusting for covariates, Asian Americans reported higher mean scores of purging, muscle building, and cognitive restraint (qs < 0.05) than Whites and NAPOC. Asian Americans also scored higher on restriction compared with Whites (qs < 0.05), as well as body dissatisfaction and negative attitudes toward obesity compared with NAPOC (qs < 0.05). These findings demonstrate the existence of racial differences among specific ED symptoms, highlighting the importance of considering these distinctions when diagnosing and treating EDs among diverse communities.

Association between food addiction and body dissatisfaction among college students: The mediating role of eating expectancies.

A positive association between food addiction (i.e., an addiction to compulsively overeat highly palatable foods) and body dissatisfaction in college students exists. However, little is known about the underlying mechanisms. Eating expectancies, one's learning history regarding the association between eating and its consequences, may provide potential pathways linking food addiction and body dissatisfaction. In the current study, five eating expectancies (i.e., eating helps manage negative affect, eating is pleasurable and useful as a reward, eating leads to feeling out of control, eating enhances cognitive competence, and eating alleviates boredom) were evaluated as potential mediators between food addiction and body dissatisfaction in 738 college students (mean age = 19.21 ± 1.63, 61.4% female). Students completed the Eating Pathology Symptoms Inventory, Yale Food Addiction Scale, and Eating Expectancy Inventory. Adjusting for sex, age, race, and body mass index, structural equation modeling was used to examine the bi-directional mediation effects of the eating expectancies between food addiction and body dissatisfaction. Results showed a bi-directional positive association between food addiction and body dissatisfaction (ß = 0.12-0.26, standard error [SE] = 0.07-0.03, all p < 0.01) that was partially mediated by the expectancy that eating leads to feeling out of control, regardless of whether body dissatisfaction was included as the independent or dependent variable (ß = 0.15-0.36, SE = 0.05-0.02, all p < 0.01). Findings suggest the need to address the influence of expecting eating to lead to feeling out of control in interventions for co-occurring food addiction and body dissatisfaction among college students.

Eating disorders in a community-based sample of women with alcohol use disorder and nicotine dependence.

BACKGROUND: Studies consistently report a higher prevalence of substance use disorders (SUDs) among women with eating disorders than control women. However, limited research exists on the prevalence of eating disorder symptoms and diagnoses in women with SUDs, especially in community-based populations. We examined the prevalence of eating disorder symptoms and diagnosis by the presence or absence of lifetime alcohol use disorder (AUD) and/or nicotine dependence (ND) in a community-based sample of women. METHODS: 3756 women (median age = 22 years) from the Missouri Adolescent Female Twin Study completed a modified semi-structured interview assessing lifetime DSM-IV psychiatric disorders and SUDs. Logistic regression models adjusted for demographic characteristics and other psychopathology, and robust standard errors accounted for the non-independence of twin data. RESULTS: In general, women with comorbid AUD and ND had a higher prevalence of eating disorder symptoms and diagnoses than women with AUD or ND Only, who in turn had a higher prevalence than those without either SUD. After adjustment for covariates, women with AUD and ND had significantly greater risk of broad anorexia nervosa (RRR = 3.17; 99 % CI = 1.35, 7.44), purging disorder (2.59; 1.24, 5.43), and numerous eating disorder symptoms than women with neither disorder. Significant differences emerged between individuals with both AUD and ND versus women with AUD Only or ND Only for some eating disorder symptoms. CONCLUSIONS: Women with lifetime AUD or ND diagnoses are at high risk for eating disorder symptoms and diagnoses, underscoring the importance of assessing eating disorder symptoms among women with these disorders.

Premenstrual symptoms as a marker of ovarian hormone sensitivity in eating disorders.

OBJECTIVE: Research indicates a link between ovarian hormones and eating pathology, suggesting that some women with an eating disorder may be ovarian hormone sensitive. Using premenstrual symptoms (PMS) as an indirect measure of ovarian hormone sensitivity, we investigated the association between 11 PMS domains and four core eating disorder symptoms: body dissatisfaction, binge eating, purging, and restriction. METHOD: Participants were young adult women (N = 455) who completed an online survey. PMS were assessed using the Daily Record of Severity of Problems and eating pathology with the Eating Pathology Symptoms Inventory. Pearson correlations were calculated between PMS domains and eating disorder symptoms followed by a stepwise regression to create a more refined model for each eating disorder symptom, including relevant covariates. RESULTS: Significant correlations between a majority of eating disorder symptoms and PMS emerged (r's = .13-.37; p < .01). Backward regression revealed significant PMS domain predictors for each symptom. The final models captured a small-to-moderate amount of variance for each eating disorder symptom (R2 = 0.06-0.25). DISCUSSION: Women who experience physical and psychological PMS may be at risk for eating disorder symptoms; PMS could be a marker of ovarian hormone sensitivity in women at risk for an eating disorder. Future studies should address mechanisms underlying this association.

Associations between eating expectancies and Eating disorder symptoms in men and women.

Eating expectancies, or learned expectations that an individual has about eating, prospectively predict eating disorder (ED) symptoms. Most studies examining eating expectancies have focused on one or two eating expectancies and their relation with bulimic symptoms. In addition, these studies have been conducted mostly in women. Thus, it is unclear whether: 1) associations between eating expectancies and ED symptoms vary between men and women, and 2) extend to ED symptoms other than bulimic symptoms. The current study (N = 197 undergraduate men and 246 undergraduate women) investigated sex variance in a model of eating expectancies and ED symptoms, including factors associated with ED symptoms (i.e., negative urgency, negative affect, alcohol use, drug use, and body mass index). Sex variance was tested using path analysis in a model including eating expectancies and associated factors, with excessive exercise, negative attitudes toward obesity, restricting, cognitive restraint, binge eating, purging, muscle building, and body dissatisfaction as dependent variables. Unconstrained (i.e., unconstrained paths across men and women) and constrained (i.e., constraining paths across men and women) models were tested. The unconstrained and constrained models differed significantly, indicating that the models varied by sex. For both sexes, eating expectancies were uniquely associated with ED symptoms. For men, Eating Manages Negative Affect was significantly associated with the most ED symptoms. In contrast, for women, Eating Leads to Feeling Out of Control was associated with the most ED symptoms. Previous findings regarding eating expectancies and ED symptoms in women may not generalize to men. Intervening on eating expectancies in a sex-specific way may help reduce specific ED symptoms.

Perceived family functioning among adolescents with and without loss of control eating.

Youth with loss of control eating (LOC) have poorer social relationships than youth without LOC. However, perceived family functioning among youth reporting LOC is relatively unexplored. We examined perceived family functioning among 990 twins (age = 17.47 ±â€¯0.71 years, 53% female) from the Colorado Center for Antisocial Drug Dependence with (n = 158) and without (n = 832) LOC. LOC was assessed with one binary item. Associations between family functioning and LOC were examined using general linear models that accounted for dependence in twin data. Girls with greater family conflict had higher odds of endorsing LOC (p = .02), but not after accounting for depressive symptoms (p = .26). Further analysis indicated that depressive symptoms mediated the association between LOC and family conflict (p = .04). This finding is consistent with an interpersonal model, which proposes that interpersonal difficulties lead to negative emotional states, which promotes LOC as a method of coping with negative affect. Family cohesion and expressiveness were not associated with LOC in girls, and none of the family functioning variables were associated with LOC in boys (ps > .05). Future studies are needed to clarify these relations and to determine any relevant treatment indications.

Editorial: Why Assessing Co-Occurring Eating Disorders and Alcohol Use in Sexual Minority Youth Is Important.

The prevalence of psychiatric disorders, such as major depression and anxiety, is higher in sexual minority individuals (eg, those who identify as gay, lesbian, or bisexual or are unsure of their orientation) than heterosexual individuals.1 Eating disorders and alcohol use also are more common in sexual minority groups, yet the extent to which they co-occur in these individuals is limited. The co-occurrence of eating and alcohol use disorders results in increased morbidity than either disorder alone2 and increased mortality for eating disorders.3 Extant studies have primarily included young women (for whom sexual identity is not assessed), suggesting that binge eating and inappropriate compensatory behaviors (eg, self-induced vomiting, diet pill misuse, and fasting) are key symptoms contributing to the co-occurrence, regardless of the primary eating disorder diagnosis. Despite its severity, treatment settings frequently overlook eating disorder and alcohol use co-occurrence and no empirically supported treatments exist to treat the disorders when they occur simultaneously. This is problematic because decreasing symptoms for one behavior might increase the presence or frequency of symptoms for the other disorder. One way to provide useful information for the treatment of eating disorder and alcohol use co-occurrence is to examine these associations within more homogeneous groups, ultimately identifying group-specific risk factors.

Illicit Drug Use, Cigarette Smoking, and Eating Disorder Symptoms: Associations in an Adolescent Twin Sample.

OBJECTIVE: Twin studies have shown that genetic factors in part explain the established relation between alcohol use (i.e., problematic use or abuse/dependence) and eating disorder symptoms in adolescent and adult females. However, studies have yet to elucidate if there are similar shared genetic factors between other aspects of substance involvement, such as illicit drug use and repeated cigarette smoking. METHOD: For those sex-specific phenotypic correlations above our threshold of .20, we used a behavioral genetic design to examine potential shared genetic overlap between self-reported lifetime illicit drug use and repeated cigarette smoking and the eating disorder symptoms of drive for thinness (DT), bulimia (BU), and body dissatisfaction (BD), as assessed with the Eating Disorder Inventory-II, in 16- to 17-year-old female and male twin pairs. RESULTS: Only phenotypic correlations with illicit drug use met our threshold for twin modeling. Small to moderate genetic correlations were observed between illicit drug use and BU in both girls and boys and between illicit drug use and DT in girls. CONCLUSIONS: Similar etiological factors are at play in the overlap between illicit drug use and certain eating disorder symptoms in girls and boys during adolescence, such that genetic factors are important for covariance. Specifically, illicit drug use was associated with bulimia nervosa symptoms in girls and boys, which parallels previous substance use research finding a genetic overlap between alcohol use and bulimia nervosa symptoms. Future research should prospectively examine developmental trajectories to further understand the etiological overlap between substance involvement and eating disorder symptoms.

The Anorexia Nervosa Genetics Initiative (ANGI): Overview and methods.

BACKGROUND: Genetic factors contribute to anorexia nervosa (AN); and the first genome-wide significant locus has been identified. We describe methods and procedures for the Anorexia Nervosa Genetics Initiative (ANGI), an international collaboration designed to rapidly recruit 13,000 individuals with AN and ancestrally matched controls. We present sample characteristics and the utility of an online eating disorder diagnostic questionnaire suitable for large-scale genetic and population research. METHODS: ANGI recruited from the United States (US), Australia/New Zealand (ANZ), Sweden (SE), and Denmark (DK). Recruitment was via national registers (SE, DK); treatment centers (US, ANZ, SE, DK); and social and traditional media (US, ANZ, SE). All cases had a lifetime AN diagnosis based on DSM-IV or ICD-10 criteria (excluding amenorrhea). Recruited controls had no lifetime history of disordered eating behaviors. To assess the positive and negative predictive validity of the online eating disorder questionnaire (ED100K-v1), 109 women also completed the Structured Clinical Interview for DSM-IV (SCID), Module H. RESULTS: Blood samples and clinical information were collected from 13,363 individuals with lifetime AN and from controls. Online diagnostic phenotyping was effective and efficient; the validity of the questionnaire was acceptable. CONCLUSIONS: Our multi-pronged recruitment approach was highly effective for rapid recruitment and can be used as a model for efforts by other groups. High online presence of individuals with AN rendered the Internet/social media a remarkably effective recruitment tool in some countries. ANGI has substantially augmented Psychiatric Genomics Consortium AN sample collection. ANGI is a registered clinical trial: clinicaltrials.govNCT01916538; https://clinicaltrials.gov/ct2/show/NCT01916538?cond=Anorexia+Nervosa&draw=1&rank=3.

Associations Between Alcohol Involvement and Drive for Thinness and Body Dissatisfaction in Adolescent Twins: A Bivariate Twin Study.

BACKGROUND: Alcohol involvement has familial associations with bulimic symptoms (i.e., binge eating, inappropriate compensatory behaviors), with several studies indicating a genetic overlap between the two. It is unclear whether overlapping familial risk with alcohol involvement extends to other eating disorder symptoms. Understanding the genetic overlap between alcohol involvement and other eating disorder symptoms may aid in more targeted interventions for comorbid alcohol use-eating disorder symptoms. Thus, we investigated associations between alcohol involvement and 2 core eating disorder symptoms: drive for thinness and body dissatisfaction in adolescent female and male twins. METHODS: We assessed 3 levels of alcohol involvement: alcohol use in the last month, having ever been intoxicated, and alcohol intoxication frequency via self-report. The Eating Disorder Inventory-II assessed drive for thinness and body dissatisfaction. Sex-specific biometrical twin modeling examined the genetic overlap between alcohol involvement and eating disorder symptoms. RESULTS: Phenotypic associations between alcohol involvement, drive for thinness, and body dissatisfaction were significantly greater in girls compared with boys. A majority of the associations between alcohol involvement, drive for thinness, and body dissatisfaction in girls, but not boys, met our threshold for twin modeling (phenotypic r > 0.20). Moderate genetic correlations were observed between the 3 aspects of alcohol involvement and drive for thinness. Moderate genetic correlations were observed between alcohol use and intoxication frequency and body dissatisfaction. CONCLUSIONS: Together with the literature on alcohol involvement and bulimic symptoms, these findings suggest a generalized association between alcohol involvement and eating disorder symptoms in girls, whereas this association may be symptom specific in boys. Genetic correlations indicate that the amount and direction of this genetic overlap differs across specific symptoms. When intervening on comorbid alcohol involvement and eating disorder symptoms, it may be important to target-specific eating disorder symptoms.