A large genetic analysis has identified DNA regions linked to binge-eating behavior and anorexia nervosa, suggesting that the two share genetic ties to other psychiatric conditions but run in opposite directions when it comes to body weight. The findings, published in Nature Mental Health, extend eating disorder genetics beyond its long focus on anorexia.
Anorexia nervosa is a condition where individuals experience an intense fear of gaining weight, leading them to severely restrict their food intake to maintain a dangerously low body weight. Binge-eating behavior involves episodes of eating unusually large amounts of food while feeling a 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, a condition in which people of normal or higher weight binge eat and then try to compensate through behaviors such as vomiting or fasting, share a moderate portion of their genetic risk. Large-scale gene-mapping studies, however, have centered on anorexia: a 2019 study by the same research consortium identified the first eight genetic regions linked to the disorder, and its authors argued that anorexia has both psychiatric and metabolic roots.
Binge eating has received far less genetic attention, even though it appears 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 (BMI), a measure of weight relative to height, pointing to 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 PsyPost. “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, which pools results from many studies that each scanned the genomes of many people for genetic variations associated with a trait. They analyzed 27 studies, 14 of which had been part of the consortium’s 2019 analysis, comparing the DNA of people who had a history of binge-eating behavior or anorexia to the DNA of people without these conditions.
The sample sizes were vast, with the binge-eating analysis including 39,279 cases and 1,227,436 controls, and the anorexia nervosa analysis including 24,223 cases and 1,243,971 controls. All participants in the primary analyses were of European ancestry.
Binge eating was defined broadly: people counted as cases if they described eating unusually large amounts of food with a sense of lost control, answered yes to a single question about binge eating, or reported a diagnosis of bulimia or binge-eating disorder, even without confirmation from a health professional. Most cases were women, making up 96 percent of the binge-eating group and 94 percent of the anorexia group.
The researchers analyzed millions of genetic markers to see if certain variations appeared more often in people with these eating behaviors. They also calculated genetic correlations, comparing the genetic patterns of the eating disorders with those of other traits like psychiatric conditions and BMI. To see if the genetic risk for eating disorders was just a side effect of genes that control weight, they mathematically separated out the genetic influence of BMI.
The analysis identified six independent genetic regions associated with binge-eating behavior. Some had previously been tied 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 run partly through binge eating.
For anorexia, 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, on a scale where 0 means no shared genetic influence and 1 means complete overlap. Both conditions shared positive genetic correlations with psychiatric issues like major depressive disorder, anxiety, and schizophrenia.
The findings are broadly in line with research covered by PsyPost in 2023, which found that people with major depression reported more disordered eating behaviors than healthy volunteers. That study measured symptoms directly in patients, whereas the new study examined overlap at the level of genetic variants.
However, the two conditions also differed psychiatrically. Anorexia, but not binge eating, was genetically linked to obsessive-compulsive disorder. 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. The genetic markers for binge eating tended to align with a higher BMI and higher body fat percentage. In contrast, the genetic markers for anorexia 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 just low body weight.
The researchers also found that these eating disorder traits are largely distinct from simple weight regulation. Using a statistical technique to separate out genetic influences shared with BMI, they found that this shared component accounted for only about 12 percent of the genetic signal for binge eating and 10 percent for anorexia, leaving the large 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.”
Finally, the team generated polygenic risk scores, which summarize a person’s overall genetic risk based on many small genetic variations. When the researchers applied anorexia risk scores built from the 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 percent of the variation in risk. This suggests that 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 some caveats to consider. The primary limitation is the heavy reliance on participants of European ancestry. Applying these findings to other global populations requires caution, as differences in genetic background and environments could influence genetic risk.
Because the studies used different ways of identifying cases, and some comparison participants were never screened for eating disorders, the groups may be more mixed than in a clinic-based study. The mostly female sample also means the results may not apply equally to men.
Diagnostic crossover is another factor to keep in mind. People’s eating disorder symptoms can change over time, meaning someone with the restricting subtype of anorexia might develop binge-eating symptoms years later. Because the data relies on cross-sectional studies that take a snapshot in time, some people in one category might eventually migrate to another, though the authors note that diagnostic crossover more likely hides real genetic differences than creates false ones.
Although the combined scores carry real information about risk at the population level, the authors note they remain weak predictors for individuals: in the European data, anorexia scores accounted for about 2.3 percent of the variation in risk and binge-eating scores only about 0.3 percent. They still cannot tell whether a particular person will develop an eating disorder without looking at other risk factors. The authors hope to conduct even larger studies incorporating multiple eating disorder diagnoses and global ancestries to build a more complete biological map.
“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.”
“But our understanding is sufficient to say that, while genetics plays a role in these conditions, neither is genetically determined, and supportive treatment and supportive social environments can help both,” he concluded.
The study, “Genomic meta-analyses of binge-eating behavior 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, Jessica K. Dennis, Christopher Hübel, Jessica S. Johnson, Yi Lu, Melissa A. Munn-Chernoff, Triinu Peters, Baiyu Qi, Katherine E. Schaumberg, Rebecca H. Signer, Karanvir Singh, Abigail R. ter Kuile, Laura M. Thornton, Jiayi Xu, Shuyang Yao, Zeynep Yilmaz, Ruyue Zhang, Johan Zvrskovec, Mohamed Abdulkadir, Ziada Ayorech, Elizabeth C. Corfield, Alexandra Havdahl, Kristi Krebs, Taralynn M. Mack, Maria Niarchou, Teemu Palviainen, Julia M. Sealock, Jessica H. Baker, Andrew W. Bergen, Andreas Birgegård, Vesna Boraska Perica, Katharina Bühren, Roland Burghardt, Matteo Cassina, Giovanni Castellini, Enrico Collantoni, James J. Crowley, Unna N. Danner, Franziska Degenhardt, Janiece E. DeSocio, Christian Dina, Monika Dmitrzak-Węglarz, Laramie E. Duncan, Karin M. Egberts, Lenka Foretova, Ina Giegling, Fragiskos Gonidakis, Scott D. Gordon, Jakob Grove, Sébastien Guillaume, Jerry D. Guintivano, Annette M. Hartmann, Konstantinos Hatzikotoulas, Stefan Herms, Hartmut Imgart, Susana Jiménez-Murcia, Antonio Julià, Gursharan Kalsi, Deborah Kaminská, Leila J. Karhunen, Hannah L. Kennedy, Kirsty M. Kiezebrink, Theresa Kolb, Janne T. Larsen, Dong Li, Lisa Lilenfeld, Mario Maj, Morten Mattingsdal, Paolo Meneguzzo, Allison L. Miller, Karen S. Mitchell, Alessio Maria Monteleone, Catherine M. Olsen, Leonid Padyukov, Richard Parker, Michaela A. Pettie, Dalila Pinto, Anu Raevuori, Samuli Ripatti, Marion E. Roberts, Paolo Santonastaso, Androula Savva, Ulrike H. Schmidt, Alexandra Schosser, Jochen Seitz, Lenka LS Slachtova, Agnieszka Slopien, Sandro Sorbi, Peter S. Straub, Jin P. Szatkiewicz, Friederike I. Tam, Elena Tenconi, Alfonso Tortorella, Artemis Tsitsika, Annemarie A. van Elburg, Gudrun Wagner, Hunna J. Watson, Roger AH Adan, Lars Alfredsson, Ole A. Andreassen, Helga Ask, Anders D. Børglum, Harry A. Brandt, David Collier, Steven Crawford, Scott Crow, Lea K. Davis, Martina de Zwaan, George Dedoussis, Danielle M. Dick, Stefan Ehrlich, Xavier Estivill, Angela Favaro, Fernando Fernández-Aranda, Krista Fischer, Andreas J. Forstner, Philip Gorwood, Hakon Hakonarson, Johannes Hebebrand, Beate Herpertz-Dahlmann, Anke Hinney, James I. Hudson, Craig Johnson, Jennifer Jordan, Allan S. Kaplan, Jaakko Kaprio, Andreas FK Karwautz, Martien JH Kas, Walter H. Kaye, James L. Kennedy, Martin A. Kennedy, Anna Keski-Rahkonen, Youl-Ri Kim, Kelly L. Klump, Mikael Landén, Stéphanie Le Hellard, Kelli Lehto, Qingqin S. Li, Jolanta Lissowska, Jurjen J. Luykx, Sarah L. Maguire, Nicholas G. Martin, Manuel Mattheisen, Sarah E. Medland, Philip Mehler, Nadia Micali, James E. Mitchell, Palmiero Monteleone, Preben Bo Mortensen, Benedetta Nacmias, Roel A. Ophoff, Hana Papezova, Nancy L. Pedersen, Liselotte V. Petersen, Luisa S. Rajcsanyi, Nicolas Ramoz, Ted Reichborn-Kjennerud, Valdo Ricca, Stephan Ripke, Dan Rujescu, Filip Rybakowski, Stephen W. Scherer, Margarita CT Slof-Op ‘t Landt, Howard Steiger, Patrick F. Sullivan, Beata Świątkowska, Eric F. van Furth, Tracey D. Wade, Thomas Werge, David C. Whiteman, D. Blake Woodside, Ya-Ke Wu, Stephan Zipfel, Cynthia M. Bulik, Laura M. Huckins, Gerome Breen, and Jonathan R.I. Coleman.
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