Jessica H. Baker

The Genetics of Eating Disorders

Over the past decade, considerable advances have been made in understanding genetic influences on eating pathology. Eating disorders aggregate in families, and twin studies reveal that additive genetic factors account for approximately 40% to 60% of liability to anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED). Molecular genetics studies have been undertaken to identify alterations in deoxyribonucleic acid sequence and/or gene expression that may be involved in the pathogenesis of disordered eating behaviors, symptoms, and related disorders and to uncover potential genetic variants that may contribute to variability of treatment response. This article provides an in-depth review of the scientific literature on the genetics of AN, BN, and BED including extant studies, emerging hypotheses, future directions, and clinical implications.

Eating disorder symptomatology and substance use disorders: prevalence and shared risk in a population based twin sample.

Objective: Research shows a significant association between eating disorders (ED) and substance use disorders (SUD). The objective of this study is to examine the prevalence, chronology, and possibility of shared familial risk between SUD and ED symptomatology. Method: Subjects included 1,206 monozygotic and 877 dizygotic adult female twins. ED symptomatology included anorexia (AN) and bulimia nervosa (BN) diagnosis, symptoms associated with diagnostic criteria, and BN symptom count. SUD included alcohol, illicit drug, and caffeine abuse/dependence. Generalized estimated equation modeling was used to examine phenotypic associations, and Choleksy decompositions were used to delineate the contribution of genes and environment to comorbidity. Results: There were no significant differences between SUD prevalence in women with AN and BN. Women with BN reported BN preceded SUD development while the reverse was true for AN. Twin analyses showed possible familial overlap between BN symptomatology and all SUD examined. Discussion: Results suggest an important difference in the chronology of EDs and SUDs. Women with BN may be turning to substances to dampen bulimic urges. Women with AN may be engaging in substance use initially in an effort to lose weight. Results also suggest familial factors contribute to the comorbidity between BN and SUD.

Genetic Risk Factors for Disordered Eating in Adolescent Males and Females

The etiologic role of genetic and environmental factors on disordered eating was examined in a sample of 15- to 17-year-old female-female, male-male, and opposite-sex twin pairs. Also assessed was whether a single factor is underlying 3 facets (body dissatisfaction, drive for thinness, bulimia) of disordered eating, including the possible importance of sex differences. Univariate model-fitting analyses indicated that genetic factors are more important for girls and environment more important for boys for body dissatisfaction and drive for thinness. A multivariate common factor analysis indicated that a single factor accounted for the association among these 3 facets of disordered eating in both sexes. However, only 50% of the genetic risk for this factor is shared between the sexes.

Pubertal development predicts eating behaviors in adolescence

OBJECTIVE Early maturing girls are at increased risk for disordered eating. However, it is unclear if the association between puberty and disordered eating continues throughout pubertal development and if a similar association is exhibited in boys. METHOD Participants included 1340 same- and 624 opposite-sex twins from the Swedish Twin Study of Child and Adolescent Development. Pubertal development was assessed at age 13-14 with the pubertal development scale. General disordered eating, measured with the eating disorder inventory-2 (EDI) was assessed at age 16-17, and dieting and purging behaviors were assessed at both ages 16-17 and 19-20. We applied analysis of variance and logistic regression analyses to determine whether pubertal development in early-to-mid adolescence predicted eating disorder-related behaviors in late adolescence and young adulthood. RESULTS Pubertal development in early-to-mid adolescence was significantly associated with EDI scores and dieting in late adolescence. No significant association was observed between pubertal development and dieting and purging in young adulthood. DISCUSSION Complex combinations of cultural and biological influences likely converge during pubertal development increasing vulnerability to disordered eating. The impact of pubertal development on disordered eating appears to be limited to the adolescent period.

Etiological overlap between obsessive‐compulsive disorder and anorexia nervosa: a longitudinal cohort, multigenerational family and twin study

Obsessive‐compulsive disorder (OCD) often co‐occurs with anorexia nervosa (AN), a comorbid profile that complicates the clinical management of both conditions. This population‐based study aimed to examine patterns of comorbidity, longitudinal risks, shared familial risks and shared genetic factors between OCD and AN at the population level. Participants were individuals with a diagnosis of OCD (N=19,814) or AN (N=8,462) in the Swedish National Patient Register between January 1992 and December 2009; their first‐, second‐ and third‐degree relatives; and population‐matched (1:10 ratio) unaffected comparison individuals and their relatives. Female twins from the population‐based Swedish Twin Register (N=8,550) were also included. Females with OCD had a 16‐fold increased risk of having a comorbid diagnosis of AN, whereas males with OCD had a 37‐fold increased risk. Longitudinal analyses showed that individuals first diagnosed with OCD had an increased risk for a later diagnosis of AN (risk ratio, RR=3.6), whereas individuals first diagnosed with AN had an even greater risk for a later diagnosis of OCD (RR=9.6). These longitudinal risks were about twice as high for males than for females. First‐ and second‐degree relatives of probands with OCD had an increased risk for AN, and the magnitude of this risk tended to increase with the degree of genetic relatedness. Bivariate twin models revealed a moderate but significant degree of genetic overlap between self‐reported OCD and AN diagnoses (ra=0.52, 95% CI: 0.26‐0.81), but most of the genetic variance was disorder‐specific. The moderately high genetic correlation supports the idea that this frequently observed comorbid pattern is at least in part due to shared genetic factors, though disorder‐specific factors are more important. These results have implications for current gene‐searching efforts and for clinical practice.

Sex differences and developmental stability in genetic and environmental influences on psychoactive substance consumption from early adolescence to young adulthood

BACKGROUND Genetic and environmental factors are important in the etiology of substance use. However, little is known about the stability of these factors across development. We aimed to answer three crucial questions about this etiology that have never been addressed in a single study: (1) Is there a general vulnerability to substance consumption from early adolescence to young adulthood? (2) If so, do the genetic and environmental influences on this vulnerability change across development? (3) Do these developmental processes differ in males and females? METHOD Subjects included 1480 twin pairs from the Swedish Twin Study of Child and Adolescent Development who have been followed since 1994. Prospective, self-reported regular smoking, alcohol intoxication and illicit drug use were assessed at ages 13-14, 16-17 and 19-20 years. Structural modeling was performed with the program Mx. RESULTS An underlying common factor accounted for the association between smoking, alcohol and illicit drug consumption for the three age groups. Common genetic and shared environmental effects showed substantial continuity. In general, as participants aged, the influence of the shared environment decreased, and genetic effects became more substance specific in their effect. CONCLUSIONS The current report answers three important questions in the etiology of substance use. The genetic and environmental risk for substance consumption is partly mediated through a common factor and is partly substance specific. Developmentally, evidence was strongest for stability of common genetic effects, with less evidence for genetic innovation. These processes seem to be the same in males and females.

A behavioral-genetic investigation of bulimia nervosa and its relationship with alcohol use disorder.

Bulimia nervosa (BN) and alcohol use disorder (AUD) frequently co-occur and may share genetic factors; however, the nature of their association is not fully understood. We assessed the extent to which the same genetic and environmental factors contribute to liability to BN and AUD. A bivariate structural equation model using a Cholesky decomposition was fit to data from 7241 women who participated in the Swedish Twin study of Adults: Genes and Environment. The proportion of variance accounted for by genetic and environmental factors for BN and AUD and the genetic and environmental correlations between these disorders were estimated. In the best-fitting model, the heritability estimates were 0.55 (95% CI: 0.37; 0.70) for BN and 0.62 (95% CI: 0.54; 0.70) for AUD. Unique environmental factors accounted for the remainder of variance for BN. The genetic correlation between BN and AUD was 0.23 (95% CI: 0.01; 0.44), and the correlation between the unique environmental factors for the two disorders was 0.35 (95% CI: 0.08; 0.61), suggesting moderate overlap in these factors. The findings from this investigation provide additional support that some of the same genetic factors may influence liability to both BN and AUD.

Intrauterine testosterone exposure and risk for disordered eating

Previous research has suggested that prenatal testosterone exposure masculinises disordered eating by comparing opposite- and same-gender twins. The objective of the current study is to replicate this finding using a sample of 439 identical and 213 fraternal females, 461 identical and 344 fraternal males, and 361 males and 371 females from opposite-gender twin pairs. Disordered eating was compared across twin types using the Eating Disorder Inventory-2. Inconsistent with previous findings, a main effect of co-twin gender was not found. Our results raise questions about the validity of prior evidence of the impact of prenatal testosterone exposure on patterns of disordered eating.

Temporal Sequence of Comorbid Alcohol Use Disorder and Anorexia Nervosa

Women with eating disorders have a significantly higher prevalence of substance use disorders than the general population. The goal of the current study was to assess the temporal pattern of comorbid anorexia nervosa (AN) and alcohol use disorder (AUD) and the impact this ordering has on symptomatology and associated features. Women were placed into one of three groups based on the presence or absence of comorbid AUD and the order of AN and AUD onset in those with both disorders: (1) AN Only, (2) AN First, and (3) AUD First. The groups were compared on psychological symptoms and personality characteristics often associated with AN, AUD, or both using general linear models. Twenty-one percent of women (n=161) with AN reported a history of AUD with 115 reporting AN onset first and 35 reporting AUD onset first. Women with binge-eating and/or purging type AN were significantly more likely to have AUD. In general, differences were found only between women with AN Only and women with AN and AUD regardless of order of emergence. Women with AN and AUD had higher impulsivity scores and higher prevalence of depression and borderline personality disorder than women with AN Only. Women with AN First scored higher on traits commonly associated with AN, whereas women with comorbid AN and AUD displayed elevations in traits more commonly associated with AUD. Results do not indicate a distinct pattern of symptomatology in comorbid AN and AUD based on the temporal sequence of the disorders.

Shared Genetic Effects Between Age at Menarche and Disordered Eating

PURPOSE An early age at menarche is associated with disordered eating in women. However, it is unclear whether they share genetic factors. The goal of the current study was to delineate the genetic correlation between age at menarche and disordered eating. METHODS Participants included 427 monozygotic and 329 dizygotic 16-17-year-old female twins from the Swedish Twin Study of Child and Adolescent Development. Disordered eating was assessed with the Eating Disorder Inventory-2. Age at menarche was assessed through self-report. A bivariate correlated factors model was used to delineate the genetic correlation between age at menarche and disordered eating. RESULTS The analysis revealed a negative genetic correlation of -.18 in the best-fit model, indicating that the genetic factors that influence younger age at menarche are associated with increased liability for disordered eating. CONCLUSIONS Future research should examine possible causes for this correlation, such as the estrogen system and gene-environment interactions.