Genetics of Anorexia Nervosa


Anorexia nervosa (AN) is a heritable disorder characterised by an extremely low body weight and food restriction that frequently onsets during adolescence. However, AN is observed across the lifespan. A majority of twin studies reveal that genetic factors, on average, account for between 40% and 60% of the liability to AN. Candidate gene studies exploring the molecular genetic basis of AN have primarily focussed on genes in the serotoninergic and dopaminergic pathways. Although no pathway or gene has been unequivocally demonstrated to play a causal role in AN, 5‐HTTLPR, 5HT2A, DRD2 and DRD4 are noteworthy candidates from the serotonin and dopamine systems. Genome‐wide association studies have not yet revealed any genes meeting genome‐wide significance for AN. However, sample sizes have been small and underpowered, underscoring the need for much larger samples.

Key Concepts:

  • Anorexia nervosa is, on average, estimated to be 40–60% heritable.

  • Chromosome 1 has received some support for harbouring a region of interest for AN.

  • Candidate gene studies of AN have provided inconclusive results.

  • Genes in the serotonin, dopamine and opioid systems have shown some positive associations with AN.

  • Genome‐wide association studies have not revealed significant findings for AN, although they have been underpowered.

  • The genetic architecture of AN is likely complex, representing a synergistic interaction between many genetic and environmental factors.

Keywords: anorexia nervosa; genetics; twin study; heritability; genes


Ando T, Komaki G, Nishimura H et al. (2010) A ghrelin gene variant may predict crossover rate from restricting‐type anorexia nervosa to other phenotypes of eating disorders: a retrospective survival analysis. Psychiatric Genetics 20(4): 153–159.

Bachner‐Melman R, Lerer E, Zohar AH et al. (2007) Anorexia nervosa, perfectionism, and dopamine D4 receptor (DRD4). American Journal of Medical Genetics Part B, Neuropsychiatric Genetics 144B(6): 748–756.

Bergen AW, van den Bree MBM, Yeager M et al. (2003) Candidate genes for anorexia nervosa in the 1p33‐36 linkage region: serotonin 1D and delta opioid receptor loci exhibit significant association to anorexia nervosa. Molecular Psychiatry 8: 397–406.

Bergen AW, Yeager M, Welch RA et al. (2005) Association of multiple DRD2 polymorphisms with anorexia nervosa. Neuropsychopharmacology 30(9): 1703–1710.

Brandys MK, Kas MJ, van Elburg AA et al. (2011) The Val66Met polymorphism of the BDNF gene in anorexia nervosa: new data and a meta‐analysis. World Journal of Biological Psychiatry. DOI: 10.3109/15622975.2011.6054706.

Brandys MK, Slof‐Op't Landt MC, van Elburg AA et al. (2012) Anorexia nervosa and the Val158Met polymorphism of the COMT gene: meta‐analysis and new data. Psychiatric Genetics 22(3): 130–136.

Brown KM, Bujac SR, Mann ET et al. (2007) Further evidence of association of OPRD1 & HTR1D polymorphisms with susceptibility to anorexia nervosa. Biological Psychiatry 61(3): 367–373.

Brown LM and Clegg DJ (2010) Central effects of estradiol in the regulation of food intake, body weight, and adiposity. Journal of Steroid Biochemistry and Molecular Biology 122(1–3): 65–73.

Campbell DA, Sundaramurthy D, Gordon D, Markham AF and Pieri LF (1999) Association between a marker in the UCP‐2/UCP‐3 gene cluster and genetic susceptibility to anorexia nervosa. Molecular Psychiatry 4: 68–70.

Castellini G, Ricca V, Lelli L et al. (2012) Association between serotonin transporter gene polymorphism and eating disorders outcome: a 6‐year follow‐up study. American Journal of Medical Genetics Part B, Neuropsychiatric Genetics 159B(5): 491–500.

Cellini E, Nacmias B, Brecelj‐Anderluh M et al. (2006) Case‐control and combined family trios analysis of three polymorphisms in the ghrelin gene in European patients with anorexia and bulimia nervosa. Psychiatric Genetics 16(2): 51–52.

Dardennes RM, Zizzari P, Tolle V et al. (2007) Family trios analysis of common polymorphisms in the obestatin/ghrelin, BDNF and AGRP genes in patients with Anorexia nervosa: association with subtype, body‐mass index, severity and age of onset. Psychoneuroendocrinology 32(2): 106–113.

Devlin B, Bacanu S, Klump K et al. (2002) Linkage analysis of anorexia nervosa incorporating behavioral covariates. Human Molecular Genetics 11(6): 689–696.

Eastwood H, Brown K, Markovic D and Pieri L (2002) Variation in the ESR1 and ESR2 genes and genetic susceptibility to anorexia nervosa. Molecular Psychiatry 7: 86–89.

Frisch A, Laufer N, Danziger Y et al. (2001) Association of anorexia nervosa with the high activity allele of the COMT gene: a family‐based study in Israeli patients. Molecular Psychiatry 6(2): 243–245.

Gorwood P, Kipman A and Foulon C (2003) The human genetics of anorexia nervosa. European Journal of Pharmacology 480(1–3): 163–170.

Grice DE, Halmi KA, Fichter MM et al. (2002) Evidence for a susceptibility gene for anorexia nervosa on chromosome 1. American Journal of Human Genetics 70(3): 787–792.

Himmerich H, Schonknecht P, Heitmann S and Sheldrick AJ (2010) Laboratory parameters and appetite regulators in patients with anorexia nervosa. Journal Psychiatric Practice 16(2): 82–92.

Hindorff LA, Sethupathy P, Junkins HA et al. (2009) Potential etiologic and functional implications of genome‐wide association loci for human diseases and traits. Proceedings of the National Academy of Sciences of the USA 106(23): 9362–9367.

Hudson JI, Hiripi E, Pope HG Jr and Kessler RC (2007) The prevalence and correlates of eating disorders in the National Comorbidity Survey Replication. Biological Psychiatry 61: 348–358.

Ishiguro H, Onaivi ES, Horiuchi Y et al. (2011) Functional polymorphism in the GPR55 gene is associated with anorexia nervosa. Synapse 65(2): 103–108.

Jonassaint CR, Szatkiewicz JP, Bulik CM et al. (2011) Absence of association between specific common variants of the obesity‐related FTO gene and psychological and behavioral eating disorder phenotypes. American Journal of Medical Genetics Part B, Neuropsychiatric Genetics 156B(4): 454–461.

Kanbur N, Mesci L, Derman O et al. (2008) Tumor necrosis factor alpha‐308 gene polymorphism in patients with anorexia nervosa. Turkish Journal of Pediatrics 50(3): 219–222.

Kim YR, Woo JM, Heo SY et al. (2009) An association study of the A218C polymorphism of the tryptophan hydroxylase 1 Gene with eating disorders in a Korean population: a pilot study. Psychiatry Investigation 6(1): 44–49.

Kindler J, Bailer U, de Zwaan M et al. (2011) No association of the neuropeptide Y (Leu7Pro) and ghrelin gene (Arg51Gln, Leu72Met, Gln90Leu) single nucleotide polymorphisms with eating disorders. Nordic Journal of Psychiatry 65(3): 203–207.

Kipman A, Bruins‐Slot L, Boni C et al. (2002) 5‐HT(2A) gene promoter polymorphism as a modifying rather than a vulnerability factor in anorexia nervosa. European Psychiatry 17(4): 227–229.

Klump KL, Miller KB, Keel PK et al. (2001) Genetic and environmental influences on anorexia nervosa syndromes in a population‐based twin sample. Psychological Medicine 31(4): 737–740.

Koronyo‐Hamaoui M, Danziger Y, Frisch A et al. (2002) Association between anorexia nervosa and the hsKCa3 gene: a family‐ based and case control study. Molecular Psychiatry 7: 82–85.

Koronyo‐Hamaoui M, Frisch A, Stein D et al. (2007) Dual contribution of NR2B subunit of NMDA receptor and SK3 Ca(2+)‐activated K+ channel to genetic predisposition to anorexia nervosa. Journal of Psychiatric Research 41(1–2): 160–167.

Koronyo‐Hamaoui M, Gak E, Stein D et al. (2004) CAG repeat polymorphism within the KCNN3 gene is a significant contributor to susceptibility to anorexia nervosa: a case‐control study of female patients and several ethnic groups in the Israeli Jewish population. American Journal of Medical Genetics Part B, Neuropsychiatric Genetics 131B(1): 76–80.

Kortegaard LS, Hoerder K, Joergensen J, Gillberg C and Kyvik KO (2001) A preliminary population‐based twin study of self‐reported eating disorder. Psychological Medicine 31(2): 361–365.

Martaskova D, Slachtova L, Kemlink D, Zahorakova D and Papezova H (2009) Polymorphisms in serotonin‐related genes in anorexia nervosa. The first study in Czech population and metaanalyses with previously performed studies. Folia Biologica 55(5): 192–197.

Merle JV, Haas V, Burghardt R et al. (2011) Agouti‐related protein in patients with acute and weight‐restored anorexia nervosa. Psychological Medicine 41(10): 2183–2192.

Monteleone P, Bifulco M, Di Filippo C et al. (2009) Association of CNR1 and FAAH endocannabinoid gene polymorphisms with anorexia nervosa and bulimia nervosa: evidence for synergistic effects. Genes, Brain, and Behavior 8(7): 728–732.

Monteleone P, Tortorella A, Castaldo E, Di Filippo C and Maj M (2006) No association of the Arg51Gln and Leu72Met polymorphisms of the ghrelin gene with anorexia nervosa or bulimia nervosa. Neuroscience Letters 398(3): 325–327.

Muller TD, Greene BH, Bellodi L et al. (2012) Fat mass and obesity‐associated gene (FTO) in eating disorders: evidence for association of the rs9939609 obesity risk allele with bulimia nervosa and anorexia nervosa. Obesity Facts 5(3): 408–419.

Muller TD, Tschop MH, Jarick I et al. (2011) Genetic variation of the ghrelin activator gene ghrelin O‐acyltransferase (GOAT) is associated with anorexia nervosa. Journal of Psychiatric Research 45(5): 706–711.

Nakabayashi K, Komaki G, Tajima A et al. (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.

Nakai Y, Hamagaki S, Takagi R, Taniguchi A and Kurimoto F (1999) Plasma concentrations of tumor necrosis factor‐alpha (TNF‐alpha) and soluble TNF receptors in patients with anorexia nervosa. Journal of Clinical Endocrinology and Metabolism 84(4): 1226–1228.

Ribases M, Gratacos M, Armengol L et al. (2003) Met66 in the brain‐derived neurotrophic factor (BDNF) precursor is associated with anorexia nervosa restrictive type. Molecular Psychiatry 8: 745–751.

Ribases M, Gratacos M, Fernandez‐Aranda F et al. (2004) Association of BDNF with anorexia, bulimia and age of onset of weight loss in six European populations. Human Molecular Genetics 13: 1205–1212.

Ribases M, Gratacos M, Fernandez‐Aranda F et al. (2005) Association of BDNF with restricting anorexia nervosa and minimum body mass index: a family‐based association study of eight European populations. European Journal of Human Genetics 13: 428–434.

Siegfried Z, Kanyas K, Latzer Y et al. (2004) Association study of cannabinoid receptor gene (CNR1) alleles and anorexia nervosa: differences between restricting and binging/purging subtypes. American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics 125B(1): 126–130.

Slof‐Op't Landt MC, Meulenbelt I, Bartels M et al. (2011) Association study in eating disorders: TPH2 associates with anorexia nervosa and self‐induced vomiting. Genes, Brain, and Behavior 10(2): 236–243.

Strober M, Freeman R, Lampert C, Diamond J and Kaye W (2000) Controlled family study of anorexia nervosa and bulimia nervosa: evidence of shared liability and transmission of partial syndromes. American Journal of Psychiatry 157(3): 393–401.

Sullivan PF, Daly MJ and O'Donovan M (2012) Genetic architectures of psychiatric disorders: the emerging picture and its implications. Nature Reviews Genetics 13(8): 537–551.

Urwin R, Bennetts B, Wilcken B et al. (2002) Anorexia nervosa (restrictive subtype) is associated with a polymorphism in the novel norepinephrine transporter gene promoter polymorphic region. Molecular Psychiatry 7: 652–657.

Versini A, Ramoz N, Le Strat Y et al. (2010) Estrogen receptor 1 gene (ESR1) is associated with restrictive anorexia nervosa. Neuropsychopharmacology 35(8): 1818–1825.

Vink T, Hinney A and van Elburg AAea. (2001) Association between an agouti‐related protein gene polymorphism and anorexia nervosa. Molecular Psychiatry 6: 325–328.

Wang K, Zhang H, Bloss CS et al. (2011) A genome‐wide association study on common SNPs and rare CNVs in anorexia nervosa. Molecular Psychiatry 16(9): 949–959.

Further Reading

Arnold C (2012) Decoding Anorexia: How Breakthroughs in Science Offer Hope for Eating Disorders. New York: Routledge.

Bulik CM (2005) Exploring the gene‐environment nexus in eating disorders. Journal of Psychiatry Neuroscience 30: 335–338.

Campbell IC, Mill J, Uher R et al. (2011) Eating disorders, gene‐environment interactions and epigenetics. Neuroscience and Biobehavioral Reviews 35(3): 784–793.

Monteleone P and Maj M (2008) Genetic susceptibility to eating disorders: associated polymorphisms and pharmacogenetic suggestions. Pharmacogenomics 9(10): 1487–1520.

Rask‐Andersen M, Olszewski PK, Levin AS et al. (2010) Molecular Mechanisms Underlying Anorexia Nervosa: Focus on human gene association studies and systems controlling food intake. Brain and Research Reviews 62: 147–164.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Baker, Jessica H, Trace, Sara E, Janson, Lauren E, and Bulik, Cynthia M(Sep 2013) Genetics of Anorexia Nervosa. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0024614]