Genetic and Environmental Risk Factors for Disordered Eating and Co-Occurring Traits

Prior studies have shown that eating disorders and disordered eating characteristics have similar contributions of genetic and environmental influences. However, few studies have identified specific genetic variants that influence these phenotypes. It is possible that the lack of replication studies is due to the focus on one particular polymorphism rather than a more comprehensive approach that includes multiple polymorphisms at a given locus. In addition, little information is known about common risk factors for eating disorders and co-occurring traits, such as substance use and personality. This dissertation uses adolescent and young adult twins and their family members from the community sample of the Colorado Center for Antisocial Drug Dependence (CADD) to investigate risk factors for disordered eating, substance use, and specific personality traits. Findings from the research examining risk factors for disordered eating provide insight into whether putative genetic variants, such as those in the serotonin transporter gene (SLC6A4), are associated with these characteristics. First, extended twin analyses were used to investigate genetic and environmental influences on two disordered eating characteristics identified from the CADD. Second, a family-based association test examined whether specific genetic variants in and near SLC6A4 were associated with disordered eating. Finally, phenotypic correlations among disordered eating, substance use, and personality traits were examined. Results from the first study suggested that individual differences in disordered eating characteristics could be explained by additive genetic and non-shared environmental influences. Findings from the second study suggested that a genetic variant upstream of the 5\u27 region of SLC6A4 was associated with a measure of weight and shape concerns and behaviors, even after controlling for multiple genetic variant testing. The final study found small phenotypic correlations between disordered eating and multiple substance use measures, and between disordered eating and specific personality traits. Implications for these findings are discussed

Anorexia Nervosa, Major Depression, and Suicide Attempts: Shared Genetic Factors

We evaluated the extent to which genetic and environmental factors influenced anorexia nervosa (AN), major depressive disorder (MDD), and suicide attempts (SA). Participants were 6,899 women from the Swedish Twin study of Adults Genes and Environment. A Cholesky decomposition assessed independent and overlapping genetic and environmental contributions to AN, MDD, and SA. Genetic factors accounted for a substantial amount of liability to all three traits; unique environmental factors accounted for most of the remaining liability. Shared genetic factors may underlie the co-expression of these traits. Results underscore the importance of assessing for signs of suicide among individuals with AN

Is the relationship between binge eating episodes and personality attributable to genetic factors?

Aspects of disordered eating and personality traits, such as neuroticism are correlated and, individually, heritable. We examined the phenotypic correlation between binge eating episodes and indices of personality (neuroticism, extraversion, openness to experience, agreeableness, conscientiousness and control/impulsivity). For correlations ≥ |0.20|, we estimated the extent to which genetic and environmental factors contributed to this correlation. Participants included 3446 European-American same-sex female twins from the Missouri Adolescent Female Twin Study (median age = 22 years). Binge eating episode was assessed via interview questions. Personality traits were assessed by self-report questionnaires. There was a significant moderate phenotypic correlation between binge eating episode and neuroticism (r = 0.33), as well as conscientiousness (r=−0.21) while other correlations were significant but smaller (r ranging from −0.14 to 0.14). Individual differences in binge eating episodes, neuroticism and conscientiousness were attributed to additive genetic influences (38% [95% confidence interval: 21%–53%], 45% [38%–52%], and 44% [0.33–0.55] respectively), with the remaining variance due to individual-specific environmental influences. Covariance was attributable to genetic (neuroticism r(g) = 0.37; conscientiousness r(g) = −0.22) and individual-specific environmental (neuroticism r(e) = 0.28; conscientiousness r(e) = −0.19) influences. Personality traits may be an early indicator of genetic vulnerability to a variety of pathological behaviors including binge eating episode. Furthermore, prior research documenting phenotypic correlations between eating disorder diagnoses and personality may stem from etiological overlap between these personality traits and aspects of disordered eating, such as binge eating episode

Genetic and environmental risk for major depression in African-American and European-American women

It is unknown whether there are racial differences in the heritability of major depressive disorder (MDD) because most psychiatric genetic studies have been conducted in samples comprised largely of white non-Hispanics. To examine potential differences between African-American (AA) and European-American (EA) young adult women in (1) DSM-IV MDD prevalence, symptomatology and risk factors and (2) genetic and/or environmental liability to MDD, we analyzed data from a large, population representative sample of twins ascertained from birth records (n= 550 AA and n=3226 EA female twins) aged 18–28 years at the time of MDD assessment by semi-structured psychiatric interview. AA women were more likely to have MDD risk factors; however, there were no significant differences in lifetime MDD prevalence between AA and EA women after adjusting for covariates (Odds Ratio = 0.88, 95% confidence interval: 0.67–1.15 ). Most MDD risk factors identified among AAs were also associated with MDD at similar magnitudes among EAs. Although the MDD heritability point estimate was higher among AA than EA women in a model with paths estimated separately by race (56%, 95% CI: 29%–78% vs. 41%, 95% CI: 29%–52%), the best-fitting model was one in which additive genetic and nonshared environmental paths for AA and EA women were constrained to be equal (A = 43%, 33%–53% and E = 57%, 47%–67%). Despite a marked elevation in the prevalence of environmental risk exposures related to MDD among AA women, there were no significant differences in lifetime prevalence or heritability of MDD between AA and EA young women

The Association of Low Parental Monitoring With Early Substance Use in European American and African American Adolescent Girls

Research indicates that low parental monitoring increases the risk for early substance use. Because low parental monitoring tends to co-occur with other familial and neighborhood factors, the specificity of the association is challenging to establish. Using logistic regression and propensity score analyses, we examined associations between low parental monitoring and early substance use in European American (EA) and African American (AA) girls, controlling for risk factors associated with low parental monitoring

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

The Anorexia Nervosa Genetics Initiative (ANGI): overview and methods

This manuscript version is made available under the CC-BY-NC-ND 4.0 license: http://creativecommons.org/licenses/by-nc-nd/4.0/ which permits use, distribution and reproduction in any medium, provided the original work is properly cited. This author accepted manuscript is made available following 12 month embargo from date of publication (October 2018) in accordance with the publisher’s archiving policyBackground 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.Please refer to published article

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

First published: 16 February 202

Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.Peer reviewe