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How Genetic Factors Influence Eating Disorders

By Dennis Gibson, MD, FACP, CEDS

Genetics & Eating Disorders

Eating disorders are known as “perfect storm” illnesses, where development is attributed to a mix of sociocultural factors, genetic predisposition, psychiatric comorbidities and personality traits.

Research is still emerging on the role genetics play in the risk for developing an eating disorder, but current studies suggest a significant portion of risk may be genetic. Most studies focus on anorexia nervosa; and genetics studies including bulimia nervosa and binge eating disorder (BED) are more rare.

Family History & Genes

Family studies quantify the extent to which genetic factors contribute to variation among individuals. Family studies suggest a familial vulnerability for eating disorders, but they cannot rule out environmental influences. Relatives of probands (the first person in a family to be identified as possibly having a genetic disorder) with anorexia have been shown to have an increased risk of eating disorders and subclinical eating disorder behavior.

Larger studies suggest up to a 12 fold increase in likelihood for anorexia nervosa. Relatives of probands with bulimia nervosa are also more likely to be diagnosed with bulimia nervosa, with a 4.4 or 9.6 times greater risk than controls.Binge eating disorder is also more likely to occur in family members of probands, but the risk is lower than those with anorexia nervosa and bulimia.

Twin studies are studies that compare identical and fraternal sets of twins to determine liability (an individual's innate tendency to develop a disease). Unlike family studies, where genetics are not identical and environment is shared, twin studies provide greater insight — identical twins share the same genes and environment while fraternal twins share the same environment and only 50% of the same genetics, allowing researchers to better separate genetic and environmental risk factors.

Twin studies have shown that identical twins are more likely to have concordant anorexia, and twins with bulimia were more likely to be concordant or have another eating disorder diagnosis. Twin studies estimate the heritability for AN to range from 0.28 to 0.74, the heritability for BN to approximate 0.6, and the heritability for BED to be around 0.4.

Adoption studies are few and far between, with only one recorded adoption study covering eating disorder pathology. Adoption studies are valuable, as biological relatives only share genetics with the proband, while the adoptive relatives only share environment. In this single study, genetic influences were a significant contributor toward the development of disordered eating while shared environmental factors did no significantly contribute.

Molecular Genetics

Molecular genetic studies, such as linkage studies, genome-wide association (GWA) studies, candidate gene studies and genome-sequencing have all been used to analyze the structure and function of genes and their role in the development of eating disorders.

Eating Disorder Linkage Studies

Linkage studies are used in gene discovery, using genetic markers to identify the chromosomal regions that may contain genes that contribute to eating disorders. This has identified several regions of interest on chromosomes 1, 2, 4, and 13, although these studies do not often identify vulnerability genes. As an example, the impact of serotonergic genes toward the development of an eating disorder remain inconclusive.

Genome-Wide Association Studies

A genome-wide association study (GWAS) is an approach that involves rapidly scanning markers across the genomes of many people to find genetic variations associated with particular diseases. Once new genetic associations are identified, researchers can use it to develop better strategies to detect, treat and prevent the disease.

Two anorexia nervosa loci (singular locus; a physical site or location within a genome) have been identified by GWAS. One study found a significant association approaching genome wide significant between a variant in the Early B-Cell Factor 1 (EBF1) gene and which may impact circulating leptin levels, consistent with the very low leptin levels in human patients with anorexia nervosa. Another study identified a region associated with autoimmune disorders.

Eating Disorder Candidate Gene Studies

Candidate gene association studies analyze the genetic variation associated with disease within a limited number of pre-specified genes. Many candidate gene studies of common variants for eating disorders have been published but none are definitive. Regardless of eating disorder type, most research has focused on homeostatic control and reward system pathways because they are hypothesized to share pathways with eating disorders, since it’s believed that healthy eating behavior is achieved through a balance of homeostatic controls and reward processes. The main pathways explored in candidate gene studies of eating disorders are as follows:

  • Homeostatic pathways
    • Leptin melanocortin pathway genes (i.e. LEP, LEPR, POMC, AGRP, MC4R, BDNF genes, as well as GHRL, FTO genes)
  • Reward-related pathways including
    • Central neurotransmission of serotonin (i.e., HTR1D, HTR2A, HTR2C, SLC6A4 genes)
    • Dopamine (i.e., DRD2, DRD4, ANKK1 genes)
    • Noradrenaline (COMT gene)
    • Opioid (OPRD1, OPRM genes)
    • Cannabinoid endogenous system (CNR1 gene)

Dysregulation of homeostatic and reward processes is observed in EDs, but it is currently unknown if alterations to these pathways are a cause or an effect.

Eating Disorder Genome Sequencing

Whole genome sequencing is the process of determining the (near) entirety of the DNA sequence of an organism's genome at a single time. A recent whole-exome/whole-genome sequencing of two multigenerational pedigrees (lineages) affected by multiple eating disorder identified the estrogen-related receptor-α (ESRRA) and the histone deacetylase 4 (HDAC4) genes as promising candidates for further study.

Eating Disorders Changing DNA

Epigenetics is the study of how behavior and environmental factors can cause changes that affect the way genes work.

Epigenetics

The most studied mechanism of epigenetics is DNA methylation, both hyper-and hypomethylation, which impacts the ability of DNA to replicate. Nutrition can impact methylation but there is currently no evidence of an epigenetic pattern with anorexia nervosa.

Even though genetic studies may not currently impact treatment for individual patients, there is still value in understanding the genetic components of eating disorders. Knowing what genes predispose individuals for eating disorders may lead to better treatment options in the future.  

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dennis gibson

Dennis Gibson, MD, FACP, CEDS

Dennis Gibson, MD, FACP, CEDS serves as the Clinical Operations Director at ACUTE. Dr. Gibson joined ACUTE in 2017 and has since dedicated his clinical efforts to the life-saving medical care of…

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