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Genetics of Eating Disorders

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Eating Disorders

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Abstract

Family and twin studies have shown that eating disorders are moderately heritable. Newer methods, such as genome-wide association studies (GWASs), are guiding molecular genetic discoveries. The majority of evidence to date has emerged from studies of anorexia nervosa (AN). The most recent GWAS on AN implicated eight regions of the genome that contain genetic risk variants and provided evidence supporting the common disease–common variant theory. The role of rare variants has also been investigated, resulting in preliminary evidence for the role of structural variation and de novo mutations in AN. Evidence from cross-disorder GWASs and genetic correlations between AN and other traits points toward a shared genetic basis between AN and psychiatric traits, especially OCD, and physical activity, educational attainment, and anthropometric and metabolic traits. Other studies have shown that genetic risk scores for AN and early-onset AN significantly predict future onset of their respective phenotypes, albeit they are too premature for clinical use. Functional genomic studies have implicated subcortical appetitive and reward circuits and genes linked to food restriction in animal models. Animal models of AN have suggested that food can act as an addictive substance, and epigenetic studies have highlighted the role of global DNA methylation in AN, pointing toward differential methylation in genes relevant to metabolism, nutrition, and psychiatric status. We conclude with a brief discussion of the pitfalls of genetics research. Nonetheless, genetic research holds promise for new and improved treatment targets and for advancing our understanding of eating disorders.

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References

  • Abdulkadir, M., Herle, M., De Stavola, B. L., Hübel, C., Santos Ferreira, D. L., Loos, R. J. F., Bryant-Waugh, R., Bulik, C. M., & Micali, N. (2020). Polygenic score for body mass index is associated with disordered eating in a general population cohort. Journal of Clinical Medicine, 9(4), 1187. https://doi.org/10.3390/jcm9041187

    Article  PubMed  PubMed Central  Google Scholar 

  • Abdulkadir, M., Hübel, C., Herle, M., Loos, R. J. F., Breen, G., Bulik, C. M., & Micali, N. (2022). Eating disorder symptoms and their associations with anthropometric and psychiatric polygenic scores. European Eating Disorders Review, 30(3), 221–236. https://doi.org/10.1002/erv.2889

    Article  PubMed  PubMed Central  Google Scholar 

  • Adams, D. M., Reay, W. R., Geaghan, M. P., & Cairns, M. J. (2021). Investigation of glycaemic traits in psychiatric disorders using Mendelian randomisation revealed a causal relationship with anorexia nervosa. Neuropsychopharmacology, 46(6), 1093–1102. https://doi.org/10.1038/s41386-020-00847-w

    Article  CAS  PubMed  Google Scholar 

  • Amico, J. A., Vollmer, R. R., Cai, H. M., Miedlar, J. A., & Rinaman, L. (2005). Enhanced initial and sustained intake of sucrose solution in mice with an oxytocin gene deletion. American Journal of Physiology: Regulatory, Integrative, and Comparative Physiology, 289(6), R1798–R1806. https://doi.org/10.1152/ajpregu.00558.2005

    Article  CAS  PubMed  Google Scholar 

  • Avena, N. M. (2009). Binge eating: Neurochemical insights from animal models. Eating Disorders: The Journal of Treatment and Prevention, 17(1), 89–92. https://doi.org/10.1080/10640260802371604

    Article  Google Scholar 

  • Babbs, R. K., Beierle, J. A., Ruan, Q. T., Kelliher, J. C., Chen, M. M., Feng, A. X., Kirkpatrick, S. L., Benitez, F. A., Rodriguez, F. A., Pierre, J. J., Anandakumar, J., Kumar, V., Mulligan, M. K., & Bryant, C. D. (2019). Cyfip1 haploinsufficiency increases compulsive-like behavior and modulates palatable food intake in mice: Dependence on Cyfip2 genetic background, parent-of origin, and sex. G3: Genes, Genomics, Genetics, 9(9), 3009–3022. https://doi.org/10.1534/g3.119.400470

    Article  CAS  Google Scholar 

  • Barré-Sinoussi, F., & Montagutelli, X. (2015). Animal models are essential to biological research: Issues and perspectives. Future Science OA, 1(4), FSO63. https://doi.org/10.4155/fso.15.63

    Article  PubMed  PubMed Central  Google Scholar 

  • Bienvenu, T., Lebrun, N., Clarke, J., Duriez, P., Gorwood, P., & Ramoz, N. (2020). De novo deleterious variants that may alter the dopaminergic reward pathway are associated with anorexia nervosa. Eating and Weight Disorders, 25(6), 1643–1650. https://doi.org/10.1007/s40519-019-00802-9

    Article  PubMed  Google Scholar 

  • Booij, L., Casey, K. F., Antunes, J. M., Szyf, M., Joober, R., Israël, M., & Steiger, H. (2015). DNA methylation in individuals with anorexia nervosa and in matched normal-eater controls: A genome-wide study. International Journal of Eating Disorders, 48(7), 874–882. https://doi.org/10.1002/eat.22374

    Article  PubMed  Google Scholar 

  • Boraska, V., Franklin, C. S., Floyd, J. A., Thornton, L. M., Huckins, L. M., Southam, L., Rayner, N. W., Tachmazidou, I., Klump, K. L., Treasure, J., Lewis, C. M., Schmidt, U., Tozzi, F., Kiezebrink, K., Hebebrand, J., Gorwood, P., Adan, R. A., Kas, M. J., Favaro, A., et al. (2014). A genome-wide association study of anorexia nervosa. Molecular Psychiatry, 19(10), 1085–1094. https://doi.org/10.1038/mp.2013.187

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bulik, C. M., Coleman, J. R. I., Hardaway, J. A., Breithaupt, L., Watson, H. J., Bryant, C. D., & Breen, G. (2022). Genetics and neurobiology of eating disorders. Nature Neuroscience, 25(5), 543–554. https://doi.org/10.1038/s41593-022-01071-z

    Article  CAS  PubMed  Google Scholar 

  • Ceccarini, M. R., Tasegian, A., Franzago, M., Patria, F. F., Albi, E., Codini, M., Conte, C., Bertelli, M., Dalla Ragione, L., Stuppia, L., & Beccari, T. (2020). 5-HT2AR and BDNF gene variants in eating disorders susceptibility. American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics, 183(3), 155–163. https://doi.org/10.1002/ajmg.b.32771

    Article  CAS  Google Scholar 

  • Chen, Z. Y., Jing, D., Bath, K. G., Ieraci, A., Khan, T., Siao, C. J., Herrera, D. G., Toth, M., Yang, C., McEwen, B. S., Hempstead, B. L., & Lee, F. S. (2006). Genetic variant BDNF (Val66Met) polymorphism alters anxiety-related behavior. Science, 314(5796), 140–143. https://doi.org/10.1126/science.1129663

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen, X., Yao, T., Cai, J., Fu, X., Li, H., & Wu, J. (2022). Systemic inflammatory regulators and 7 major psychiatric disorders: A two-sample Mendelian randomization study. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 116, 110534. https://doi.org/10.1016/j.pnpbp.2022.110534

    Article  CAS  PubMed  Google Scholar 

  • Colantuoni, C., Schwenker, J., McCarthy, J., Rada, P., Ladenheim, B., Cadet, J. L., Schwartz, G. J., Moran, T. H., & Hoebel, B. G. (2001). Excessive sugar intake alters binding to dopamine and mu-opioid receptors in the brain. Neuroreport, 12(16), 3549–3552. https://doi.org/10.1097/00001756-200111160-00035

    Article  CAS  PubMed  Google Scholar 

  • Coombes, B. J., Markota, M., Mann, J. J., Colby, C., Stahl, E., Talati, A., Pathak, J., Weissman, M. M., McElroy, S. L., Frye, M. A., & Biernacka, J. M. (2020). Dissecting clinical heterogeneity of bipolar disorder using multiple polygenic risk scores. Translational Psychiatry, 10(1), 314. https://doi.org/10.1038/s41398-020-00996-y

    Article  PubMed  PubMed Central  Google Scholar 

  • Cross-Disorder Group of the Psychiatric Genomics Consortium. (2019). Genomic relationships, novel loci, and pleiotropic mechanisms across eight psychiatric disorders. Cell, 179(7), 1469–1482.e1411. https://doi.org/10.1016/j.cell.2019.11.020

    Article  CAS  PubMed Central  Google Scholar 

  • Duncan, L., Yilmaz, Z., Gaspar, H., Walters, R., Goldstein, J., Anttila, V., Bulik-Sullivan, B., Ripke, S., Consortium, E. D. W. G. o. t. P. G., Thornton, L., Hinney, A., Daly, M., Sullivan, P., Zeggini, E., Breen, G., & Bulik, C. (2017). Significant locus and metabolic genetic correlations revealed in genome-wide association study of anorexia nervosa. American Journal of Psychiatry, 174(9), 850–858. https://doi.org/10.1176/appi.ajp.2017.16121402.

  • Frieling, H., Gozner, A., Römer, K. D., Lenz, B., Bönsch, D., Wilhelm, J., Hillemacher, T., de Zwaan, M., Kornhuber, J., & Bleich, S. (2007). Global DNA hypomethylation and DNA hypermethylation of the alpha synuclein promoter in females with anorexia nervosa. Molecular Psychiatry, 12(3), 229–230. https://doi.org/10.1038/sj.mp.4001931

    Article  CAS  PubMed  Google Scholar 

  • Gale, C. R., Hagenaars, S. P., Davies, G., Hill, W. D., Liewald, D. C., Cullen, B., Penninx, B. W., Boomsma, D. I., Pell, J., McIntosh, A. M., Smith, D. J., Deary, I. J., & Harris, S. E. (2016). Pleiotropy between neuroticism and physical and mental health: Findings from 108 038 men and women in UK biobank. Translational Psychiatry, 6(4), e791. https://doi.org/10.1038/tp.2016.56

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Giel, K. E., Bulik, C. M., Fernandez-Aranda, F., Hay, P., Keski-Rahkonen, A., Schag, K., Schmidt, U., & Zipfel, S. (2022). Binge eating disorder. Nature Reviews Disease Primers, 8(1), 16. https://doi.org/10.1038/s41572-022-00344-y

    Article  PubMed  PubMed Central  Google Scholar 

  • González, L. M., Mota-Zamorano, S., García-Herráiz, A., López-Nevado, E., & Gervasini, G. (2021). Genetic variants in dopamine pathways affect personality dimensions displayed by patients with eating disorders. Eating and Weight Disorders, 26(1), 93–101. https://doi.org/10.1007/s40519-019-00820-7

    Article  PubMed  Google Scholar 

  • Gratacòs, M., González, J. R., Mercader, J. M., de Cid, R., Urretavizcaya, M., & Estivill, X. (2007). Brain-derived neurotrophic factor Val66Met and psychiatric disorders: Meta-analysis of case-control studies confirm association to substance-related disorders, eating disorders, and schizophrenia. Biological Psychiatry, 61(7), 911–922. https://doi.org/10.1016/j.biopsych.2006.08.025

    Article  CAS  PubMed  Google Scholar 

  • Howard, D., Negraes, P., Voineskos, A. N., Kaplan, A. S., Muotri, A. R., Duvvuri, V., & French, L. (2020). Molecular neuroanatomy of anorexia nervosa. Scientific Reports, 10(1), 11411. https://doi.org/10.1038/s41598-020-67692-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hübel, C., Gaspar, H. A., Coleman, J. R. I., Finucane, H., Purves, K. L., Hanscombe, K. B., Prokopenko, I., Graff, M., Ngwa, J. S., Workalemahu, T., O’Reilly, P. F., Bulik, C. M., & Breen, G. (2019a). Genomics of body fat percentage may contribute to sex bias in anorexia nervosa. American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics, 180(6), 428–438. https://doi.org/10.1002/ajmg.b.32709

    Article  CAS  PubMed  Google Scholar 

  • Hübel, C., Gaspar, H. A., Coleman, J. R. I., Hanscombe, K. B., Purves, K., Prokopenko, I., Graff, M., Ngwa, J. S., Workalemahu, T., O’Reilly, P. F., Bulik, C. M., & Breen, G. (2019b). Genetic correlations of psychiatric traits with body composition and glycemic traits are sex- and age-dependent. Nature Communications, 10(1), 5765. https://doi.org/10.1038/s41467-019-13544-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hübel, C., Abdulkadir, M., Herle, M., Loos, R. J. F., Breen, G., Bulik, C. M., & Micali, N. (2021). One size does not fit all. Genomics differentiates among anorexia nervosa, bulimia nervosa, and binge-eating disorder. International Journal of Eating Disorders, 54(5), 785–793. https://doi.org/10.1002/eat.23481

    Article  PubMed  Google Scholar 

  • Huckins, L. M., Hatzikotoulas, K., Southam, L., Thornton, L. M., Steinberg, J., Aguilera-McKay, F., Treasure, J., Schmidt, U., Gunasinghe, C., Romero, A., Curtis, C., Rhodes, D., Moens, J., Kalsi, G., Dempster, D., Leung, R., Keohane, A., Burghardt, R., Ehrlich, S., et al. (2018). Investigation of common, low-frequency and rare genome-wide variation in anorexia nervosa. Molecular Psychiatry, 23(5), 1169–1180. https://doi.org/10.1038/mp.2017.88

    Article  CAS  PubMed  Google Scholar 

  • Jean, A., Laurent, L., Delaunay, S., Doly, S., Dusticier, N., Linden, D., Neve, R., Maroteaux, L., Nieoullon, A., & Compan, V. (2017). Adaptive control of dorsal raphe by 5-HT4 in the prefrontal cortex prevents persistent hypophagia following stress. Cell Reports, 21(4), 901–909. https://doi.org/10.1016/j.celrep.2017.10.003

    Article  CAS  PubMed  Google Scholar 

  • Johansen, J. E., Broberger, C., Lavebratt, C., Johansson, C., Kuhar, M. J., Hökfelt, T., & Schalling, M. (2000). Hypothalamic CART and serum leptin levels are reduced in the anorectic (anx/anx) mouse. Brain Research. Molecular Brain Research, 84(1–2), 97–105. https://doi.org/10.1016/s0169-328x(00)00228-x

    Article  CAS  PubMed  Google Scholar 

  • Johansson, T., Birgegård, A., Zhang, R., Bergen, S. E., Landén, M., Petersen, L. V., Bulik, C. M., & Hübel, C. (2022). Polygenic association with severity and long-term outcome in eating disorder cases. Translational Psychiatry, 12(1), 61. https://doi.org/10.1038/s41398-022-01831-2

    Article  PubMed  PubMed Central  Google Scholar 

  • Kesselmeier, M., Pütter, C., Volckmar, A.-L., Baurecht, H., Grallert, H., Illig, T., Ismail, K., Ollikainen, M., Silén, Y., Keski-Rahkonen, A., Bulik, C. M., Collier, D. A., Zeggini, E., Hebebrand, J., Scherag, A., Hinney, A., & Gcan, & Wtccc. (2018). High-throughput DNA methylation analysis in anorexia nervosa confirms TNXB hypermethylation. World Journal of Biological Psychiatry, 19(3), 187–199. https://doi.org/10.1080/15622975.2016.1190033

    Article  Google Scholar 

  • Kim, Y., Trace, S. E., Crowley, J. J., Brownley, K. A., Hamer, R. M., Pisetsky, D. S., Sullivan, P. F., & Bulik, C. M. (2013). Assessment of gene expression in peripheral blood using RNAseq before and after weight restoration in anorexia nervosa. Psychiatry Research, 210(1), 287–293. https://doi.org/10.1016/j.psychres.2013.05.026

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kim, D. Y., Yu, J., Mui, R. K., Niibori, R., Taufique, H. B., Aslam, R., Semple, J. W., & Cordes, S. P. (2017). The tyrosine kinase receptor Tyro3 enhances lifespan and neuropeptide Y (Npy) neuron survival in the mouse anorexia (anx) mutation. Disease Models & Mechanisms, 10(5), 581–595. https://doi.org/10.1242/dmm.027433

    Article  CAS  Google Scholar 

  • Koomar, T., Thomas, T. R., Pottschmidt, N. R., Lutter, M., & Michaelson, J. J. (2021). Estimating the prevalence and genetic risk mechanisms of ARFID in a large autism cohort. Frontiers in Psychiatry, 12, 668297. https://doi.org/10.3389/fpsyt.2021.668297

    Article  PubMed  PubMed Central  Google Scholar 

  • Li, D., Chang, X., Connolly, J. J., Tian, L., Liu, Y., Bhoj, E. J., Robinson, N., Abrams, D., Li, Y. R., Bradfield, J. P., Kim, C. E., Li, J., Wang, F., Snyder, J., Lemma, M., Hou, C., Wei, Z., Guo, Y., Qiu, H., et al. (2017). A genome-wide association study of anorexia nervosa suggests a risk locus implicated in dysregulated leptin signaling. Scientific Reports, 7(1), 3847. https://doi.org/10.1038/s41598-017-01674-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lilenfeld, L. R., Kaye, W. H., Greeno, C. G., Merikangas, K. R., Plotnicov, K., Pollice, C., Rao, R., Strober, M., Bulik, C. M., & Nagy, L. (1998). A controlled family study of anorexia nervosa and bulimia nervosa: Psychiatric disorders in first-degree relatives and effects of proband comorbidity. Archives of General Psychiatry, 55(7), 603–610. https://doi.org/10.1001/archpsyc.55.7.603

    Article  CAS  PubMed  Google Scholar 

  • Lindfors, C., Katz, A., Selander, L., Johansen, J. E., Marconi, G., Schalling, M., Hökfelt, T., Berggren, P. O., Zaitsev, S., & Nilsson, I. A. (2015). Glucose intolerance and pancreatic β-cell dysfunction in the anorectic anx/anx mouse. American Journal of Physiology: Endocrinology and Metabolism, 309(4), E418–E427. https://doi.org/10.1152/ajpendo.00081.2015

    Article  CAS  PubMed  Google Scholar 

  • Liu, X., Kelsoe, J. R., & Greenwood, T. A. (2016). A genome-wide association study of bipolar disorder with comorbid eating disorder replicates the SOX2-OT region. Journal of Affective Disorders, 189, 141–149. https://doi.org/10.1016/j.jad.2015.09.029

    Article  CAS  PubMed  Google Scholar 

  • Lloyd, E. C., Sallis, H. M., Verplanken, B., Haase, A. M., & Munafò, M. R. (2020). Understanding the nature of association between anxiety phenotypes and anorexia nervosa: A triangulation approach. BMC Psychiatry, 20(1), 495. https://doi.org/10.1186/s12888-020-02883-8

    Article  PubMed  PubMed Central  Google Scholar 

  • Lutter, M., Bahl, E., Hannah, C., Hofammann, D., Acevedo, S., Cui, H., McAdams, C. J., & Michaelson, J. J. (2017a). Novel and ultra-rare damaging variants in neuropeptide signaling are associated with disordered eating behaviors. PLoS One, 12(8), e0181556. https://doi.org/10.1371/journal.pone.0181556

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lutter, M., Khan, M. Z., Satio, K., Davis, K. C., Kidder, I. J., McDaniel, L., Darbro, B. W., Pieper, A. A., & Cui, H. (2017b). The eating-disorder associated HDAC4(A778T) mutation alters feeding behaviors in female mice. Biological Psychiatry, 81(9), 770–777. https://doi.org/10.1016/j.biopsych.2016.09.024

    Article  CAS  PubMed  Google Scholar 

  • Madra, M., & Zeltser, L. M. (2016). BDNF-Val66Met variant and adolescent stress interact to promote susceptibility to anorexic behavior in mice. Translational Psychiatry, 6(4), e776. https://doi.org/10.1038/tp.2016.35

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Maltais, L. J., Lane, P. W., & Beamer, W. G. (1984). Anorexia, a recessive mutation causing starvation in preweanling mice. Journal of Heredity, 75(6), 468–472. https://doi.org/10.1093/oxfordjournals.jhered.a109987

    Article  CAS  PubMed  Google Scholar 

  • McGuire, A. L., Gabriel, S., Tishkoff, S. A., Wonkam, A., Chakravarti, A., Furlong, E. E. M., Treutlein, B., Meissner, A., Chang, H. Y., López-Bigas, N., Segal, E., & Kim, J. S. (2020). The road ahead in genetics and genomics. Nature Reviews Genetics, 21(10), 581–596. https://doi.org/10.1038/s41576-020-0272-6

  • Mercader, J. M., Lozano, J. J., Sumoy, L., Dierssen, M., Visa, J., Gratacòs, M., & Estivill, X. (2008). Hypothalamus transcriptome profile suggests an anorexia-cachexia syndrome in the anx/anx mouse model. Physiological Genomics, 35(3), 341–350. https://doi.org/10.1152/physiolgenomics.90255.2008

    Article  CAS  PubMed  Google Scholar 

  • Mullins, N., Kang, J., Campos, A. I., Coleman, J. R. I., Edwards, A. C., Galfalvy, H., Levey, D. F., Lori, A., Shabalin, A., Starnawska, A., Su, M. H., Watson, H. J., Adams, M., Awasthi, S., Gandal, M., Hafferty, J. D., Hishimoto, A., Kim, M., Okazaki, S., et al. (2022). Dissecting the shared genetic architecture of suicide attempt, psychiatric disorders, and known risk factors. Biological Psychiatry, 91(3), 313–327. https://doi.org/10.1016/j.biopsych.2021.05.029

    Article  PubMed  Google Scholar 

  • Munn-Chernoff, M. A., Johnson, E. C., Chou, Y. L., Coleman, J. R. I., Thornton, L. M., Walters, R. K., Yilmaz, Z., Baker, J. H., Hübel, C., Gordon, S., Medland, S. E., Watson, H. J., Gaspar, H. A., Bryois, J., Hinney, A., Leppä, V. M., Mattheisen, M., Ripke, S., Yao, S., et al. (2021). Shared genetic risk between eating disorder- and substance-use-related phenotypes: Evidence from genome-wide association studies. Addiction Biology, 26(1), e12880. https://doi.org/10.1111/adb.12880

    Article  CAS  PubMed  Google Scholar 

  • Nagata, J. M., Braudt, D. B., Domingue, B. W., Bibbins-Domingo, K., Garber, A. K., Griffiths, S., & Murray, S. B. (2019). Genetic risk, body mass index, and weight control behaviors: Unlocking the triad. International Journal of Eating Disorders, 52(7), 825–833. https://doi.org/10.1002/eat.23083

    Article  PubMed  Google Scholar 

  • Nakabayashi, K., Komaki, G., Tajima, A., Ando, T., Ishikawa, M., Nomoto, J., Hata, K., Oka, A., Inoko, H., Sasazuki, T., & Shirasawa, S. (2009). Identification of novel candidate loci for anorexia nervosa at 1q41 and 11q22 in Japanese by a genome-wide association analysis with microsatellite markers. Journal of Human Genetics, 54(9), 531–537. https://doi.org/10.1038/jhg.2009.74

    Article  CAS  PubMed  Google Scholar 

  • Negraes, P. D., Cugola, F. R., Herai, R. H., Trujillo, C. A., Cristino, A. S., Chailangkarn, T., Muotri, A. R., & Duvvuri, V. (2017). Modeling anorexia nervosa: Transcriptional insights from human iPSC-derived neurons. Translational Psychiatry, 7(3), e1060. https://doi.org/10.1038/tp.2017.37

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nestler, E. J., & Hyman, S. E. (2010). Animal models of neuropsychiatric disorders. Nature Neuroscience, 13(10), 1161–1169. https://doi.org/10.1038/nn.2647

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • NHGRI-EBI GWAS Catalog. (2022). GWAS catalog. Retrieved March 8, 2022, from https://www.ebi.ac.uk/gwas/

  • Palmeira, L., Cunha, M., Padez, C., Alvarez, M., Pinto-Gouveia, J., & Manco, L. (2019). Association study of variants in genes FTO, SLC6A4, DRD2, BDNF and GHRL with binge eating disorder (BED) in Portuguese women. Psychiatry Research, 273, 309–311. https://doi.org/10.1016/j.psychres.2019.01.047

    Article  CAS  PubMed  Google Scholar 

  • Peters, T., Antel, J., Naaresh, R., Laabs, B.-H., Föcker, M., Albers, N., Bühlmeier, J., Hinney, A., Libuda, L., & Hebebrand, J. (2021). Suggestive evidence for causal effect of leptin levels on risk for anorexia nervosa: Results of a Mendelian randomization study [Original research]. Frontiers in Genetics, 12, 733606. https://doi.org/10.3389/fgene.2021.733606

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Qin, Y., Havulinna, A. S., Liu, Y., Jousilahti, P., Ritchie, S. C., Tokolyi, A., Sanders, J. G., Valsta, L., Brożyńska, M., Zhu, Q., Tripathi, A., Vázquez-Baeza, Y., Loomba, R., Cheng, S., Jain, M., Niiranen, T., Lahti, L., Knight, R., Salomaa, V., et al. (2022). Combined effects of host genetics and diet on human gut microbiota and incident disease in a single population cohort. Nature Genetics, 54(2), 134–142. https://doi.org/10.1038/s41588-021-00991-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Saffrey, R., Novakovic, B., & Wade, T. D. (2014). Assessing global and gene specific DNA methylation in anorexia nervosa: A pilot study. International Journal of Eating Disorders, 47(2), 206–210. https://doi.org/10.1002/eat.22200

    Article  PubMed  Google Scholar 

  • Scherag, S., Hebebrand, J., & Hinney, A. (2010). Eating disorders: The current status of molecular genetic research. European Child and Adolescent Psychiatry, 19(3), 211–226. https://doi.org/10.1007/s00787-009-0085-9

    Article  PubMed  Google Scholar 

  • Sild, M., & Booij, L. (2019). Histone deacetylase 4 (HDAC4): A new player in anorexia nervosa? Molecular Psychiatry, 24(10), 1425–1434. https://doi.org/10.1038/s41380-019-0366-8

    Article  CAS  PubMed  Google Scholar 

  • Spangler, R., Wittkowski, K. M., Goddard, N. L., Avena, N. M., Hoebel, B. G., & Leibowitz, S. F. (2004). Opiate-like effects of sugar on gene expression in reward areas of the rat brain. Brain Research. Molecular Brain Research, 124(2), 134–142. https://doi.org/10.1016/j.molbrainres.2004.02.013

    Article  CAS  PubMed  Google Scholar 

  • Steiger, H., Booij, L., Kahan, E., McGregor, K., Thaler, L., Fletcher, E., Labbe, A., Joober, R., Israël, M., Szyf, M., Agellon, L. B., Gauvin, L., St-Hilaire, A., & Rossi, E. (2019). A longitudinal, epigenome-wide study of DNA methylation in anorexia nervosa: Results in actively ill, partially weight-restored, long-term remitted and non-eating-disordered women. Journal of Psychiatry and Neuroscience, 44(3), 205–213. https://doi.org/10.1503/jpn.170242

    Article  PubMed  PubMed Central  Google Scholar 

  • Thornton, L. M., Mazzeo, S. E., & Bulik, C. M. (2011). The heritability of eating disorders: Methods and current findings. Current Topics in Behavioral Neurosciences, 6, 141–156. https://doi.org/10.1007/7854_2010_91

    Article  PubMed  PubMed Central  Google Scholar 

  • Tremolizzo, L., Conti, E., Bomba, M., Uccellini, O., Rossi, M. S., Marfone, M., Corbetta, F., Santarone, M. E., Raggi, M. E., Neri, F., Ferrarese, C., & Nacinovich, R. (2014). Decreased whole-blood global DNA methylation is related to serum hormones in anorexia nervosa adolescents. World Journal of Biological Psychiatry, 15(4), 327–333. https://doi.org/10.3109/15622975.2013.860467

    Article  CAS  Google Scholar 

  • Wang, K., Zhang, H., Bloss, C. S., Duvvuri, V., Kaye, W., Schork, N. J., Berrettini, W., & Hakonarson, H. (2011). A genome-wide association study on common SNPs and rare CNVs in anorexia nervosa. Molecular Psychiatry, 16(9), 949–959. https://doi.org/10.1038/mp.2010.107

    Article  CAS  PubMed  Google Scholar 

  • Watson, H. J., Yilmaz, Z., Thornton, L. M., Hübel, C., Coleman, J. R. I., Gaspar, H. A., Bryois, J., Hinney, A., Leppä, V. M., Mattheisen, M., Medland, S. E., Ripke, S., Yao, S., Giusti-Rodríguez, P., Hanscombe, K. B., Purves, K. L., Adan, R. A. H., Alfredsson, L., Ando, T., et al. (2019). Genome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa. Nature Genetics, 51(8), 1207–1214. https://doi.org/10.1038/s41588-019-0439-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Watson, H. J., Palmos, A. B., Hunjan, A., Baker, J. H., Yilmaz, Z., & Davies, H. L. (2021a). Genetics of eating disorders in the genome-wide era. Psychological Medicine, 51(13), 2287–2297. https://doi.org/10.1017/s0033291720005474

    Article  PubMed  PubMed Central  Google Scholar 

  • Watson, H. J., Thornton, L. M., Yilmaz, Z., Baker, J. H., Coleman, J. R. I., Adan, R. A. H., Alfredsson, L., Andreassen, O. A., Ask, H., Berrettini, W. H., Boehnke, M., Boehm, I., Boni, C., Buehren, K., Bulant, J., Burghardt, R., Chang, X., Cichon, S., Cone, R. D., et al. (2021b). Common genetic variation and age at onset of anorexia nervosa. Biological Psychiatry: Global Open Science, 2(4), 368–378. https://doi.org/10.1016/j.bpsgos.2021.09.001

    Article  PubMed  Google Scholar 

  • Welch, A. C., Zhang, J., Lyu, J., McMurray, M. S., Javitch, J. A., Kellendonk, C., & Dulawa, S. C. (2021). Dopamine D2 receptor overexpression in the nucleus accumbens core induces robust weight loss during scheduled fasting selectively in female mice. Molecular Psychiatry, 26(8), 3765–3777. https://doi.org/10.1038/s41380-019-0633-8

    Article  CAS  PubMed  Google Scholar 

  • Yang, J., Fan, Y., Yan, B., Zhao, B., Qian, L., Gao, F., Ma, Q., Yang, L., Wang, W., Bai, L., Zhu, F., & Ma, X. (2022). Mendelian randomization analyses reveal novel drug targets for anorexia nervosa. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 112, 110427. https://doi.org/10.1016/j.pnpbp.2021.110427

    Article  CAS  PubMed  Google Scholar 

  • Yilmaz, Z., Szatkiewicz, J. P., Crowley, J. J., Ancalade, N., Brandys, M. K., van Elburg, A., de Kovel, C. G. F., Adan, R. A. H., Hinney, A., Hebebrand, J., Gratacos, M., Fernandez-Aranda, F., Escaramis, G., Gonzalez, J. R., Estivill, X., Zeggini, E., Sullivan, P. F., & Bulik, C. M. (2017). Exploration of large, rare copy number variants associated with psychiatric and neurodevelopmental disorders in individuals with anorexia nervosa. Psychiatric Genetics, 27(4), 152–158. https://doi.org/10.1097/ypg.0000000000000172

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yilmaz, Z., Halvorsen, M., Bryois, J., Yu, D., Thornton, L. M., Zerwas, S., Micali, N., Moessner, R., Burton, C. L., Zai, G., Erdman, L., Kas, M. J., Arnold, P. D., Davis, L. K., Knowles, J. A., Breen, G., Scharf, J. M., Nestadt, G., Mathews, C. A., et al. (2020). Examination of the shared genetic basis of anorexia nervosa and obsessive-compulsive disorder. Molecular Psychiatry, 25(9), 2036–2046. https://doi.org/10.1038/s41380-018-0115-4

    Article  CAS  PubMed  Google Scholar 

  • Yilmaz, Z., Schaumberg, K., Halvorsen, M., Goodman, E. L., Brosof, L. C., Crowley, J. J., Mathews, C. A., Mattheisen, M., Breen, G., Bulik, C. M., Micali, N., & Zerwas, S. C. (in press). Predicting eating disorder and anxiety symptoms using disorder-specific and transdiagnostic polygenic scores for anorexia nervosa and obsessive-compulsive disorder. Psychological Medicine. https://doi.org/10.1017/s0033291721005079

  • Yuan, S., Xiong, Y., Michaëlsson, M., Michaëlsson, K., & Larsson, S. C. (2021). Genetically predicted education attainment in relation to somatic and mental health. Scientific Reports, 11(1), 4296. https://doi.org/10.1038/s41598-021-83801-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

H.W. acknowledges support from US National Institute of Mental Health grants R01 MH120170 (PI: Cynthia Bulik) and U01 MH109528 (PI: Patrick Sullivan). H.D. is supported by an Economic and Social Research Council (ESRC) studentship. A.P. is supported by the National Institute for Health Research (NIHR) Biomedical Research Centre at the South London and Maudsley National Health Service (NHS) Foundation Trust.

Author information

Authors and Affiliations

  1. Department of Psychiatry, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    Hunna J. Watson

  2. Division of Paediatrics, School of Medicine, The University of Western Australia, Perth, WA, Australia

    Hunna J. Watson

  3. Discipline of Psychology, Curtin University, Perth, WA, Australia

    Hunna J. Watson

  4. Social, Genetic & Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK

    Helena L. Davies & Alish B. Palmos

  5. UK National Institute for Health Research Biomedical Research Centre for Mental Health, South London and Maudsley Hospital, London, UK

    Alish B. Palmos

Authors
  1. Hunna J. Watson
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  2. Helena L. Davies
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  3. Alish B. Palmos
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Corresponding author

Correspondence to Hunna J. Watson .

Editor information

Editors and Affiliations

  1. University College London, London, UK

    Paul Robinson

  2. School of Psychology, Flinders University, Adelaide, SA, Australia

    Tracey Wade

  3. Klinik für Psychiatrie, Psychosomatik, Uniklinik der RWTH Aachen, Aachen, Nordrhein-Westfalen, Germany

    Beate Herpertz-Dahlmann

  4. Department of Psychiatry-IDIBELL, University of Barcelona, Barcelona, Spain

    Fernando Fernandez-Aranda

  5. Dept of Psychological Med IoPPN, Kings College London, London, UK

    Janet Treasure

  6. School of Medicine and Health Sciences, University of North Dakota, Fargo, USA

    Steve Wonderlich

Section Editor information

  1. Section of Eating Disorders, Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, United Kingdom

    Hubertus Himmerich

  2. Department of Medicine, Surgery and Dentistry ‘Scuola Medica Salernitana’, University of Salerno, Salerno, Italy

    Palmiero Monteleone

Glossary

Array

A small glass plate containing a “chip” which, on its surface, has a collection of microscopic DNA spots known as “probes.” DNA is applied to this surface, and the probes identify the sequence of DNA.

Common variants

Genetic variations in the DNA sequence that occur in more than 1% of the population.

Copy number variants (CNVs)

The DNA sequence can vary in ways other than SNPs; a CNV refers to variation in the number of copies of a particular gene across individuals.

De novo variants

A genetic variation that has newly occurred in an individual due to a mutation in one of their parents’ reproductive cells.

DNA methylation

A heritable alteration in the pattern of gene expression without a change in the underlying DNA sequence and that is caused by environmental factors, such as viral infections, psychosocial stress, dietary intake, air pollution, cigarette smoke, and alcohol exposure.

Genotyping

A laboratory technique of determining the DNA sequence at a specific position (i.e., a genotype) using DNA microarrays.

Impute

A statistical technique, based on linkage disequilibrium patterns, that infers the alleles of SNPs that have not been genotyped on an array.

Loci

The specific, physical locations on a chromosome of a particular gene or collection of variants. GWAS risk loci contain at least one genome-wide significant variant and other variants that are correlated and are inherited together in a block.

Missense variants

Genetic variation via a single base pair substitution that leads to the production of a different amino acid than the originally produced amino acid.

Rare variants

Genetic variations in the DNA sequence that occur in less than 1% of the population.

Sequencing

A laboratory technique of determining the exact sequence of the nucleotide bases in DNA, either via a targeted sequencing panel which focuses on a specific set of genes or via whole-genome sequencing.

Single-nucleotide polymorphisms (SNPs)

SNPs are the most common way in which people vary in their DNA and refer to variation at a single base pair position in a DNA sequence.

Whole-exome sequencing

An alternative approach to whole-genome sequencing in which only the exons (regions of DNA that code for proteins) are sequenced. Exons (together named the “exome”) make up approximately 1–2% of the human genome, thus whole-exome sequencing is faster and less expensive than whole-genome sequencing.

Whole-genome sequencing

A laboratory technique of determining the exact sequence of the nucleotide bases in DNA across the entire genome, including introns (sections of DNA that do not code for specific proteins).

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Watson, H.J., Davies, H.L., Palmos, A.B. (2023). Genetics of Eating Disorders. In: Robinson, P., Wade, T., Herpertz-Dahlmann, B., Fernandez-Aranda, F., Treasure, J., Wonderlich, S. (eds) Eating Disorders. Springer, Cham. https://doi.org/10.1007/978-3-030-97416-9_44-1

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  • DOI: https://doi.org/10.1007/978-3-030-97416-9_44-1

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  • Print ISBN: 978-3-030-97416-9

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