A large genetic analysis has identified DNA regions linked to binge-eating behaviour and anorexia nervosa, suggesting that the two conditions share genetic ties to other psychiatric disorders while moving in opposite directions on body weight. The study, published in Nature Mental Health, extends the field of eating-disorder genetics beyond its long emphasis on anorexia nervosa.
Anorexia nervosa is a condition characterised by an intense fear of gaining weight, leading to severely restricted food intake in an effort to maintain an unusually low body weight. Binge eating involves episodes of consuming unusually large amounts of food with a sense of loss of control.
Eating disorders also overlap, and people often move from one diagnosis to another over time. A 2010 twin study found that anorexia and bulimia nervosa share a moderate portion of their genetic risk. Large-scale gene-mapping studies have previously centred on anorexia, with a 2019 study identifying the first eight genetic regions linked to the disorder and suggesting that anorexia has both psychiatric and metabolic roots.
Binge eating has attracted less genetic attention, despite its presence across several eating disorders. A 2021 study by members of the same network found that people with binge-type eating disorders tended to carry more genetic variants linked to higher body mass index, underscoring the need to map binge eating’s genetics directly.
The new study was led by Jet D. Termorshuizen of Karolinska Institutet and Helena L. Davies and Sang-Hyuck Lee of King’s College London, who contributed equally, with Jonathan Coleman, a senior lecturer in statistical genetics at King’s College London, among its senior authors. The work was carried out by the Eating Disorders Working Group of the Psychiatric Genomics Consortium, an international research collaboration.
“We had previously carried out a large genetic study of anorexia nervosa and we wanted to expand this and implicate more regions of the genome as associated with this disorder,” Coleman told the researchers. “This is valuable because it provides useful genetic information that others can use to study anorexia nervosa more deeply. However, we also wanted to extend beyond anorexia nervosa and also beyond diagnoses (which are based on grouping observed symptoms rather than being based in biology).”
“For that reason, we wanted to carry out a large genetic study of binge eating, as this is a key, under-studied symptom that is present across different eating disorders (anorexia nervosa, bulimia nervosa, binge-eating disorder) in different contexts (notably, the relationship with BMI is different across these disorders),” he added. “Having a large genetic study of binge eating would allow us to understand how the genetics of an eating behavior (binge eating) related to those of an eating disorder (anorexia nervosa), as well as how a common eating symptom (binge eating) related to other common symptoms and conditions such as body composition measures.”
The researchers conducted a genome-wide association meta-analysis, pooling results from 27 studies that scanned the genomes of many people for genetic variations associated with a trait. They analysed data from 39,279 binge-eating cases and 1,227,436 controls, and 24,223 anorexia nervosa cases and 1,243,971 controls. All participants in the primary analyses were of European ancestry.
Binge eating was defined broadly: cases included individuals who described eating unusually large amounts of food with a sense of lost control, answered yes to a single binge-question, or reported a diagnosis of bulimia or binge-eating disorder, even without clinical confirmation. Most cases were women, making up 96 per cent of the binge-eating group and 94 per cent of the anorexia group.
The researchers analysed millions of genetic markers to see if certain variations appeared more often in people with these eating behaviours. They also calculated genetic correlations, comparing the genetic patterns of the eating disorders with those of other traits such as psychiatric conditions and BMI, and they separated the genetic influence of BMI to see if the risk for eating disorders lay beyond weight regulation.
The analysis identified six independent genetic regions associated with binge-eating behaviour. Some had previously been linked to smoking, risk-taking, and the age at which girls have their first period. One lies near FTO, a gene region well known for its links to obesity; it was associated with binge eating but not with anorexia, and the authors suggest that FTO’s connection to higher BMI may partly operate through binge eating.
For anorexia nervosa, the researchers identified eight genetic regions: six that had appeared in the 2019 study and two new ones. Because the new analysis reused much of the same data, the repeat findings are not fully independent confirmation, and two regions from the earlier study no longer reached the threshold for significance. The team also found one region specifically tied to the restricting subtype of anorexia, in which people limit food intake without regular binge eating or purging.
When comparing the conditions, binge eating and anorexia shared some genetic influences. They showed a genetic correlation of 0.46, a measure of the extent to which the same genetic variants influence two traits. Both conditions shared positive genetic correlations with psychiatric issues such as major depressive disorder, anxiety and schizophrenia.
The findings align broadly with research previously reported, which noted that people with major depression reported more disordered eating behaviours. However, the two conditions also differed psychiatrically. Anorexia, but not binge eating, was genetically linked to obsessive-compulsive disorder, while binge eating had a stronger link to ADHD and, unlike anorexia, was genetically linked to smoking, problem drinking and general risk tolerance.
Despite their shared psychiatric links, binge eating and anorexia displayed opposing genetic correlations with body measurements. Genetic markers for binge eating tended to align with a higher BMI and higher body fat percentage, whereas anorexia markers were associated with a lower BMI and lower body fat percentage, though anorexia showed no genetic overlap with naturally being very thin, suggesting its genetics reflect more than simply low body weight.
The researchers also found that these eating-disorder traits are largely distinct from simple weight regulation. Using a statistical method to remove BMI-shared influences, they found that this shared component accounted for about 12 per cent of the genetic signal for binge eating and 10 per cent for anorexia, leaving the majority independent of body weight genetics.
“Anorexia nervosa is not just a consequence of a genetic predisposition to low body weight, and similarly binge eating is not just a response to a genetic predisposition to high body weight,” Coleman explained. “Each has genetic links to the other, and to other psychiatric disorders and traits, but each has unique genetic features too.”
The team also generated polygenic risk scores, which summarise a person’s overall genetic risk based on many small variations. When they applied anorexia risk scores built from European data to two small studies from Japan and Korea, with about 150 anorexia cases combined, higher scores were linked to higher odds of anorexia, though they explained only about 1.3 per cent of the variation. This suggests some genetic factors for anorexia are shared across ancestries.
“The effects of individual variants on psychiatric traits and disorders in general are very small, but there are a lot of them, and together their effects become similar in size to other risk factors like adverse life events,” Coleman noted. “That is also true for anorexia nervosa and for binge eating.”
“Speaking practically, those individual effects are not very important – most people with the risk version of any given variant won’t binge eat,” he said. “However, the combined set of variants (what we call a polygenic score) has a moderate effect, and we hope that further research can show that it can be useful in future alongside known non-genetic risk factors like family history and history of life events.”
As with all research, there are caveats. The primary limitation is the heavy reliance on participants of European ancestry, so applying these findings to other populations requires caution. Differences in genetic background and environments could influence genetic risk.
Because the studies employed different case-identification methods, and some comparison participants were never screened for eating disorders, the groups may be more mixed than in clinic-based studies. The predominantly female sample also means the results may not apply equally to men.
Diagnostic crossover is another factor: people’s eating-disorder symptoms can change over time, meaning someone with the restricting subtype of anorexia might develop binge-eating symptoms years later. The authors note that diagnostic crossover more likely hides real genetic differences than creates false ones.
Although the combined scores carry information about risk at the population level, they remain weak predictors for individuals: in the European data, anorexia scores accounted for about 2.3 per cent of the variation in risk and binge-eating scores about 0.3 per cent. The researchers emphasise that genetics alone cannot determine whether someone will develop an eating disorder and advocate integrating genetic findings with family history and life events.
“It is also important that people understand that this is very much work in progress,” Coleman said. “We don’t fully understand the genetics of either anorexia nervosa or binge eating, and we are still a long way off being able to use genetics to help treat these conditions.”
The study, Genomic meta-analyses of binge-eating behaviour and anorexia nervosa yield insights into the unique and shared biology of eating disorder phenotypes, was authored by Jet D. Termorshuizen, Helena L. Davies, Sang-Hyuck Lee and numerous colleagues from institutions including Karolinska Institutet and King’s College London, among others.
