Skip to main content
SpringerLink
Log in

A next generation sequencing gene panel for use in the diagnosis of anorexia nervosa

  • Original Article
  • Published:
Eating and Weight Disorders - Studies on Anorexia, Bulimia and Obesity Aims and scope Submit manuscript

Abstract

Purpose

The aim of this study was to increase knowledge of genes associated with anorexia nervosa (AN) and their diagnostic offer, using a next generation sequencing (NGS) panel for the identification of genetic variants. The rationale underlying this test is that we first analyze the genes associated with syndromic forms of AN, then genes that were found to carry rare variants in AN patients who had undergone segregation analysis, and finally candidate genes intervening in the same molecular pathways or identified by GWAS or in mouse models.

Methods

We developed an NGS gene panel and used it to screen 68 Italian AN patients (63 females, 5 males). The panel included 162 genes. Family segregation study was conducted on available relatives of probands who reported significant genetic variants.

Results

In our analysis, we found potentially deleterious variants in 2 genes (PDE11A and SLC25A13) associated with syndromic forms of anorexia and predicted deleterious variants in the following 12 genes: CD36, CACNA1C, DRD4, EPHX2, ESR1, GRIN2A, GRIN3B, LRP2, NPY4R, PTGS2, PTPN22 and SGPP2. Furthermore, by Sanger sequencing of the promoter region of NNAT, we confirmed the involvement of this gene in the pathogenesis of AN. Family segregation studies further strengthened the possible causative role of CACNA1C, DRD4, GRIN2A, PTGS2, SGPP2, SLC25A13 and NNAT genes in AN etiology.

Conclusion

The major finding of our study is the confirmation of the involvement of the NNAT gene in the pathogenesis of AN; furthermore, this study suggests that NGS-based testing can play an important role in the diagnostic evaluation of AN, excluding syndromic forms and increasing knowledge of the genetic etiology of AN.

Level of evidence

Level I, experimental study.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Availability of data and materials

The variants reported in this manuscript were submitted to the ClinVar database (https://www.ncbi.nlm.nih.gov/clinvar/).

References

  1. Treasure J, Zipfel S, Micali N, Wade T, Stice E, Claudino A, Schmidt U, Frank GK, Bulik CM, Wentz E (2015) Anorexia nervosa. Nat Rev Dis Primers 1:15074. https://doi.org/10.1038/nrdp.2015.74

    Article  PubMed  Google Scholar 

  2. Watson HJ, Yilmaz Z, Thornton LM, Hübel C, Coleman JRI, Gaspar HA, Bulik CM (2019) Genome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa. Nat Genet 51:1207–1214. https://doi.org/10.1038/s41588-019-0439-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Zipfel S, Giel KE, Bulik CM, Hay P, Schmidt U (2015) Anorexia nervosa: aetiology, assessment, and treatment. Lancet Psychiatry 2:1099–1111. https://doi.org/10.1016/S2215-0366(15)00356-9

    Article  PubMed  Google Scholar 

  4. Smink FR, van Hoeken D, Hoek HW (2012) Epidemiology of eating disorders: incidence, prevalence and mortality rates. Curr Psychiatry Rep 14:406–414. https://doi.org/10.1007/s11920-012-0282-y

    Article  PubMed  PubMed Central  Google Scholar 

  5. Precone V, Beccari T, Stuppia L, Baglivo M, Paolacci S, Manara E, Miggiano GAD, Falsini B, Trifirò A, Zanlari A, Herbst KL, Unfer V, Bertelli M, Geneob Project (2019) Taste, olfactory and texture related genes and food choices: Implications on health status. Eur Rev Med Pharmacol Sci 23:1305–1321. https://doi.org/10.26355/eurrev_201902_17026

    Article  CAS  PubMed  Google Scholar 

  6. Precone V, Paolacci S, Beccari T, Dalla Ragione L, Stuppia L, Baglivo M, Guerri G, Manara E, Tonini G, Herbst KL, Unfer V, Bertelli M (2020) Pheromone receptors and their putative ligands: possible role in humans. Eur Rev Med Pharmacol Sci 24:2140–2150. https://doi.org/10.26355/eurrev_202002_20394

    Article  CAS  PubMed  Google Scholar 

  7. Ceccarini MR, Tasegian A, Franzago M, Patria FF, 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. Am J Med Genet B Neuropsychiatr Genet 183:155–163. https://doi.org/10.1002/ajmg.b.32771

    Article  CAS  PubMed  Google Scholar 

  8. Avena NM, Bocarsly ME (2012) Dysregulation of brain reward systems in eating disorders: neurochemical information from animal models of binge eating, bulimia nervosa, and anorexia nervosa. Neuropharmacology 63:87–96. https://doi.org/10.1016/j.neuropharm.2011.11.010

    Article  CAS  PubMed  Google Scholar 

  9. Capasso A, Milano W, Cauli O (2018) Changes in the peripheral endocannabinoid system as a risk factor for the development of eating disorders. Endocr Metab Immune Disord Drug Targets 18:325–332. https://doi.org/10.2174/1871530318666180213112406

    Article  CAS  PubMed  Google Scholar 

  10. La Bella V, Gizzi G, Albi E, Codini M, Marucci S, Dalla Ragione L, Beccari T, Ceccarini MR (2021) Vitamin D3 as possible diagnostic marker of eating disorders. EuroBiotech J 5:24–33. https://doi.org/10.2478/ebtj-2021-0005

    Article  Google Scholar 

  11. Al Massadi O, Nogueiras R, Dieguez C, Girault JA (2019) Ghrelin and food reward. Neuropharmacology 148:131–138. https://doi.org/10.1016/j.neuropharm.2019.01.001

    Article  CAS  PubMed  Google Scholar 

  12. Moskowitz L, Weiselberg E (2017) Anorexia nervosa/atypical anorexia nervosa. Curr Probl Pediatr Adolesc Health Care 47:70–84. https://doi.org/10.1016/j.cppeds.2017.02.003

    Article  PubMed  Google Scholar 

  13. Paolacci S, Kiani AK, Manara E, Beccari T, Ceccarini MR, Stuppia L, Chiurazzi P, Dalla Ragione L, Bertelli M (2020) Genetic contributions to the etiology of anorexia nervosa: New perspectives in molecular diagnosis and treatment. Mol Genet Genomic Med 8:e1244. https://doi.org/10.1002/mgg3.1244

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Shih PA, Woodside DB (2016) Contemporary views on the genetics of anorexia nervosa. Eur Neuropsycho pharmacol 26:663–673. https://doi.org/10.1016/j.euroneuro.2016.02.008

    Article  CAS  Google Scholar 

  15. Himmerich H, Bentley J, Kan C, Treasure J (2019) Genetic risk factors for eating disorders: an update and insights into pathophysiology. Ther Adv Psychopharmacol 9:2045125318814734. https://doi.org/10.1177/2045125318814734

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Watson HJ, Palmos AB, Hunjan A, Baker JH, Yilmaz Z, Davies HL (2021) Genetics of eating disorders in the genome-wide era. Psychol Med. https://doi.org/10.1017/S0033291720005474

    Article  PubMed  Google Scholar 

  17. Michael JE, Bulik CM, Hart SJ, Doyle L, Austin J (2020) Perceptions of genetic risk, testing, and counseling among individuals with eating disorders. Int J Eat Disord 53:1496–1505. https://doi.org/10.1002/eat.23333

    Article  PubMed  Google Scholar 

  18. Naureen Z, Beccari T, Marks RS, Brown R, Lorusso L, Pheby D, Miertus S, Herbst KL, Stuppia L, Henehan G, Falsini B, Lumer L, Dundar M, Bertelli M, Study Group IB (2020) Ethics committees for clinical experimentation at international level with a focus on Italy. Acta Biomed 91:e2020016. https://doi.org/10.23750/abm.v91i13-S.10643

    Article  PubMed  PubMed Central  Google Scholar 

  19. Curtis D, Adlington K, Bhui KS (2019) Pursuing parity: Genetic tests for psychiatric conditions in the UK National Health Service. Br J Psychiatry 214:248–250. https://doi.org/10.1192/bjp.2019.48

    Article  PubMed  Google Scholar 

  20. Foldi CJ, Liknaitzky P, Williams M, Oldfield BJ (2020) Rethinking therapeutic strategies for anorexia nervosa: insights from psychedelic medicine and animal models. Front Neurosci 14:43. https://doi.org/10.3389/fnins.2020.00043

    Article  PubMed  PubMed Central  Google Scholar 

  21. Marceddu G, Dallavilla T, Guerri G, Manara E, Chiurazzi P, Bertelli M (2019) PipeMAGI: an integrated and validated workflow for analysis of NGS data for clinical diagnostics. Eur Rev Med Pharmacol Sci 23:6753–6765. https://doi.org/10.26355/eurrev_201908_18566

    Article  CAS  PubMed  Google Scholar 

  22. Salpietro CD, Briuglia S, Merlino MV, Di Bella C, Rigoli L (2003) A mitochondrial DNA mutation (A3243G mtDNA) in a family with cyclic vomiting. Eur J Pediatr 162:727–728. https://doi.org/10.1007/s00431-003-1280-1

    Article  PubMed  Google Scholar 

  23. Horvath A, Boikos S, Giatzakis C, Robinson-White A, Groussin L, Griffin KJ, Stein E, Levine E, Delimpasi G, Hsiao HP, Keil M, Heyerdahl S, Matyakhina L, Libè R, Fratticci A, Kirschner LS, Cramer K, Gaillard RC, Bertagna X, Carney JA, Bertherat J, Bossis I, Stratakis CA (2006) A genome-wide scan identifies mutations in the gene encoding phosphodiesterase 11A4 (PDE11A) in individuals with adrenocortical hyperplasia. Nat Genet 38:794–800. https://doi.org/10.1038/ng1809

    Article  CAS  PubMed  Google Scholar 

  24. Newell-Price J, Trainer P, Besser M, Grossman A (1998) The diagnosis and differential diagnosis of Cushing’s syndrome and pseudo-Cushing’s states. Endocr Rev 19:647–672. https://doi.org/10.1210/edrv.19.5.0346

    Article  CAS  PubMed  Google Scholar 

  25. Sawicka N, Gryczyńska M, Sowiński J, Tamborska-Zedlewska M, Ruchała M (2013) Two diagnoses become one? Rare case report of anorexia nervosa and Cushing’s syndrome. Neuropsychiatr Dis Treat 9:431–435. https://doi.org/10.2147/NDT.S40398

    Article  PubMed  PubMed Central  Google Scholar 

  26. Verty AN, Evetts MJ, Crouch GJ, McGregor IS, Stefanidis A, Oldfield BJ (2011) The cannabinoid receptor agonist THC attenuates weight loss in a rodent model of activity-based anorexia. Neuropsychopharmacology 36:1349–1358. https://doi.org/10.1038/npp.2011.19

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Scherma M, Satta V, Collu R, Boi MF, Usai P, Fratta W, Fadda P (2017) Cannabinoid CB1/CB2 receptor agonists attenuate hyperactivity and body weight loss in a rat model of activity-based anorexia. Br J Pharmacol 174:2682–2695. https://doi.org/10.1111/bph.13892

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Monteleone P, Bifulco M, Di Filippo C, Gazzerro P, Canestrelli B, Monteleone F, Proto MC, Di Genio M, Grimaldi C, Maj M (2009) Association of CNR1 and FAAH endocannabinoid gene polymorphisms with anorexia nervosa and bulimia nervosa: evidence for synergistic effects. Genes Brain Behav 8:728–732. https://doi.org/10.1111/j.1601-183X.2009.00518.x

    Article  CAS  PubMed  Google Scholar 

  29. Ando T, Tamura N, Mera T, Morita C, Takei M, Nakamoto C, Koide M, Hotta M, Naruo T, Kawai K, Nakahara T, Yamaguchi C, Nagata T, Ookuma K, Okamoto Y, Yamanaka T, Kiriike N, Ichimaru Y, Ishikawa T, Komaki G, Japanese Genetic Research Group For Eating Disorders (2014) Association of the c.385C>A (p.Pro129Thr) polymorphism of the fatty acid amide hydrolase gene with anorexia nervosa in the Japanese population. Mol Genet Genomic Med 2:313–318. https://doi.org/10.1002/mgg3.69

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Siegfried Z, Kanyas K, Latzer Y, Karni O, Bloch M, Lerer B, Berry EM (2004) Association study of cannabinoid receptor gene (CNR1) alleles and anorexia nervosa: Differences between restricting and bingeing/purging subtypes. Am J Med Genet 125:126–130. https://doi.org/10.1002/ajmg.b.20089

    Article  Google Scholar 

  31. Takeuchi S, Yazaki M, Yamada S, Fukuyama T, Inui A, Iwasaki Y, Ikeda S (2015) An adolescent case of citrin deficiency with severe anorexia mimicking anorexia nervosa. Pediatrics 136:e530–e534. https://doi.org/10.1542/peds.2014-4172

    Article  PubMed  Google Scholar 

  32. Lombardi L, Blanchet C, Poirier K, Lebrun N, Ramoz N, Rose Moro M, Gorwood P, Bienvenu T (2019) Anorexia nervosa is associated with Neuronatin variants. Psychiatr Genet 29:103–110. https://doi.org/10.1097/YPG.0000000000000224

    Article  CAS  PubMed  Google Scholar 

  33. Gil S, Youn BS, Byun K, Huang H, Namkoong C, Jang PG, Lee JY, Jo YH, Kang GM, Kim HK, Shin MS, Pietrzik CU, Lee B, Kim YB, Kim MS (2013) Clusterin and LRP2 are critical components of the hypothalamic feeding regulatory pathway. Nat Commun 4:1862. https://doi.org/10.1038/ncomms2896

    Article  CAS  PubMed  Google Scholar 

  34. Wang K, Zhang H, Bloss C, Duvvuri V, Kaye W, Schork NJ, Berrettini W, Hakonarson H, Price Foundation Collaborative Group (2011) A genome-wide association study on common SNPs and rare CNVs in anorexia nervosa. Mol Psychiatry 16:949–959. https://doi.org/10.1038/mp.2010.107

    Article  CAS  PubMed  Google Scholar 

  35. Clarke TK, Crist RC, Doyle GA, Weiss AR, Brandt H, Crawford S, Crow S, Fichter MM, Halmi KA, Johnson C, Kaplan AS, La Via M, Mitchell JE, Strober M, Rotondo A, Treasure J, Woodside DB, Keel P, Klump KL, Lilenfeld L, Plotnicov K, Magistretti PJ, Bergen AW, Kaye WH, Schork NJ, Berrettini WH (2014) Characterization of genetic variation in the VGLL4 gene in anorexia nervosa. Psychiatr Genet 24:183–184. https://doi.org/10.1097/YPG.0000000000000040

    Article  PubMed  PubMed Central  Google Scholar 

  36. Gervasini G, Gordillo I, García-Herráiz A, Flores I, Jiménez M, Monge M, Carrillo JA (2013) Influence of dopamine polymorphisms on the risk for anorexia nervosa and associated psychopathological features. J Clin Psychopharmacol 33:551–555. https://doi.org/10.1097/JCP.0b013e3182970469

    Article  CAS  PubMed  Google Scholar 

  37. Bienvenu T, Lebrun N, Clarke J, Duriez P, Gorwood P, Ramoz N (2019) Exome sequencing in a familial form of anorexia nervosa supports multigenic etiology. J Neural Transm (Vienna) 126:1505–1511. https://doi.org/10.1007/s00702-019-02056-2

    Article  CAS  Google Scholar 

  38. Frieling H, Römer KD, Scholz S, Mittelbach F, Wilhelm J, De Zwaan M, Jacoby GE, Kornhuber J, Hillemacher T, Bleich S (2010) Epigenetic dysregulation of dopaminergic genes in eating disorders. Int J Eat Disord 43:577–583. https://doi.org/10.1002/eat.20745

    Article  PubMed  Google Scholar 

  39. Jatana N, Thukral L, Latha N (2016) Structural signatures of DRD4 mutants revealed using molecular dynamics simulations: implications for drug targeting. J Mol Model 22:14. https://doi.org/10.1007/s00894-015-2868-x

    Article  CAS  PubMed  Google Scholar 

  40. Wade TD, Gordon S, Medland S, Bulik CM, Heath AC, Montgomery GW, Martin NG (2013) Genetic variants associated with disordered eating. Int J Eat Disord 46:594–608. https://doi.org/10.1002/eat.22133

    Article  PubMed  PubMed Central  Google Scholar 

  41. Newman JW, Morisseau C, Hammock BD (2005) Epoxide hydrolases: their roles and interactions with lipid metabolism. Prog Lipid Res 44:1–51. https://doi.org/10.1016/j.plipres.2004.10.001

    Article  CAS  PubMed  Google Scholar 

  42. Scott-Van Zeeland AA, Bloss CS, Tewhey R et al (2014) Evidence for the role of EPHX2 gene variants in anorexia nervosa. Mol Psychiatry 19:724–732. https://doi.org/10.1038/mp.2013.91

    Article  CAS  PubMed  Google Scholar 

  43. GeneCards. Available online: https://www.genecards.org/cgi-bin/carddisp.pl?gene=ESR1&keywords=esr1. Accessed 1 Apr 2021

  44. Versini A, Ramoz N, Le Strat Y, Scherag S, Ehrlich S, Boni C, Hinney A, Hebebrand J, Romo L, Gorwood GJD, P, (2010) Estrogen receptor 1 gene (ESR1) is associated with restrictive anorexia nervosa. Neuropsychopharmacology 35:1818–1825. https://doi.org/10.1038/npp.2010.49

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Le Foll C, Dunn-Meynell A, Musatov S, Magnan C, Levin BE (2013) FAT/CD36: a major regulator of neuronal fatty acid sensing and energy homeostasis in rats and mice. Diabetes 62:2709–2716. https://doi.org/10.2337/db12-1689

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Betzenhauser MJ, Pitt GS, Antzelevitch C (2015) Calcium channel mutations in cardiac arrhythmia syndromes. Curr Mol Pharmacol 8:133–142. https://doi.org/10.2174/1874467208666150518114857

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Janzen ML, Malhi N, Laksman ZWM, Puyat J, Krahn AD, Hawkins NM (2018) The QT interval in anorexia nervosa: a meta-analysis. JACC Clin Electrophysiol 4:839–841. https://doi.org/10.1016/j.jacep.2018.01.019

    Article  PubMed  Google Scholar 

  48. Takimoto Y, Yoshiuchi K, Kumano H, Yamanaka G, Sasaki T, Suematsu H, Nagakawa Y, Kuboki T (2004) QT interval and QT dispersion in eating disorders. Psychother Psychosom 73:324–328

    Article  Google Scholar 

  49. Padfield GJ, Escudero CA, DeSouza AM, Steinberg C, Gibbs K, Puyat JH, Lam PY, Sanatani S, Sherwin E, Potts JE, Sandor G, Krahn AD (2016) Characterization of myocardial repolarization reserve in adolescent females with anorexia nervosa. Circulation 133:557–565. https://doi.org/10.1161/CIRCULATIONAHA.115.016697

    Article  CAS  PubMed  Google Scholar 

  50. Giovinazzo S, Sukkar SG, Rosa GM, Zappi A, Bezante GP, Balbi M, Brunelli C (2019) Anorexia nervosa and heart disease: a systematic review. Eat Weight Disord 24:199–207. https://doi.org/10.1007/s40519-018-0567-1

    Article  PubMed  Google Scholar 

  51. Meczekalski B, Podfigurna-Stopa A, Katulski K (2013) Long-term consequences of anorexia nervosa. Maturitas 75:215–220. https://doi.org/10.1016/j.maturitas.2013.04.014

    Article  PubMed  Google Scholar 

  52. Sykes L, Haddon J, Lancaster TM, Sykes A, Azzouni K, Ihssen N, Moon AL, Lin TE, Linden DE, Owen MJ, O’Donovan MC, Humby T, Wilkinson LS, Thomas KL, Hall J (2019) Genetic variation in the psychiatric risk gene CACNA1C modulates reversal learning across species. Schizophr Bull 45:1024–1032. https://doi.org/10.1093/schbul/sby146

    Article  PubMed  Google Scholar 

  53. Scherma M, Fattore L, Castelli MP, Fratta W, Fadda P (2014) The role of the endocannabinoid system in eating disorders: neurochemical and behavioural preclinical evidence. Curr Pharm Des 20:2089–2099

    Article  CAS  Google Scholar 

  54. Liu J, Wang L, Harvey-White J, Osei-Hyiaman D, Razdan R, Gong Q, Chan AC, Zhou Z, Huang BX, Kim HY, Kunos G (2006) A biosynthetic pathway for anandamide. Proc Natl Acad Sci USA 103:13345–13350

    Article  CAS  Google Scholar 

  55. Adams J, Crosbie J, Wigg K, Ickowicz A, Pathare T, Roberts W, Malone M, Schachar R, Tannock R, Kennedy JL, Barr CL (2004) Glutamate receptor, ionotropic, N-methyl D-aspartate 2A (GRIN2A) gene as a positional candidate for attention-deficit/hyperactivity disorder in the 16p13 region. Mol Psychiatry 9:494–499. https://doi.org/10.1038/sj.mp.4001455

    Article  CAS  PubMed  Google Scholar 

  56. Hopf FW (2017) Do specific NMDA receptor subunits act as gateways for addictive behaviors? Genes Brain Behav 16:118–138. https://doi.org/10.1111/gbb.12348

    Article  CAS  PubMed  Google Scholar 

  57. Mechelhoff D, van Noort BM, Weschke B, Bachmann CJ, Wagner C, Pfeiffer E, Winter S (2015) Anti-NMDA receptor encephalitis presenting as atypical anorexia nervosa: an adolescent case report. Eur Child Adolesc Psychiatry 24:1321–1324. https://doi.org/10.1007/s00787-015-0682-8

    Article  PubMed  Google Scholar 

  58. Robinette TM, Nicholatos JW, Francisco AB, Brooks KE, Diao RY, Sorbi S, Ricca V, Nacmias B, Brieño-Enríquez MA, Libert S (2020) SIRT1 accelerates the progression of activity-based anorexia. Nat Commun 11:2814. https://doi.org/10.1038/s41467-020-16348-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Dantzer R (2001) Cytokine-induced sickness behavior: mechanisms and implications. Ann N Y Acad Sci 933:222–234. https://doi.org/10.1111/j.1749-6632.2001.tb05827.x

    Article  CAS  PubMed  Google Scholar 

  60. Pecchi E, Dallaporta M, Thirion S, Salvat C, Berenbaum F, Jean A, Troadec JD (2006) Involvement of central microsomal prostaglandin E synthase-1 in IL-1beta-induced anorexia. Physiol Genom 25:485–492. https://doi.org/10.1152/physiolgenomics.00306.2005

    Article  CAS  Google Scholar 

  61. Nilsson A, Elander L, Hallbeck M, ÖrtegrenKugelberg U, Engblom D, Blomqvist A (2017) The involvement of prostaglandin E2 in interleukin-1β evoked anorexia is strain dependent. Brain Behav Immun 60:27–31. https://doi.org/10.1016/j.bbi.2016.06.014

    Article  CAS  PubMed  Google Scholar 

  62. Jesudason DR, Monteiro MP, McGowan BM, Neary NM, Park AJ, Philippou E, Small CJ, Frost GS, Ghatei MA, Bloom SR (2007) Low-dose pancreatic polypeptide inhibits food intake in man. Br J Nutr 97:426–429. https://doi.org/10.1017/S0007114507336799

    Article  CAS  PubMed  Google Scholar 

  63. Fetissov SO, Kopp J, Hökfelt T (2004) Distribution of NPY receptors in the hypothalamus. Neuropeptides 38:175–188. https://doi.org/10.1016/j.npep.2004.05.009

    Article  CAS  PubMed  Google Scholar 

  64. MGI. Available online: http://www.informatics.jax.org/marker/MGI:105374. Accessed 1 Apr 2021

  65. Bienvenu T, Lebrun N, Clarke J, Duriez P, Gorwood P, Ramoz N (2019) Exome sequencing in a familial form of anorexia nervosa supports multigenic etiology. J Neural Transm 126:1505–1511. https://doi.org/10.1007/s00702-019-02056-2

    Article  CAS  PubMed  Google Scholar 

  66. Cui H, Moore J, Ashimi SS, Mason BL, Drawbridge JN, Han S, Hing B, Matthews A, McAdams CJ, Darbro BW, Pieper AA, Waller DA, Xing C, Lutter M (2013) Eating disorder predisposition is associated with ESRRA and HDAC4 mutations. J Clin Invest 123:4706–4713. https://doi.org/10.1172/JCI71400

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. GeneCards. Available online: https://www.genecards.org/cgi-bin/carddisp.pl?gene=NNAT&keywords=nnat. Accessed 1 Apr 2021

  68. Hatakeyama M, Nakagami T, Yasui-Furukori N (2014) Adrenal Cushing’s syndrome may resemble eating disorders. Gen Hosp Psychiatry 36:760.e9–10. https://doi.org/10.1016/j.genhosppsych.2014.06.006

    Article  PubMed  Google Scholar 

  69. Andries A, Støving RK (2011) Cannabinoid-1 receptor agonists: A therapeutic option in severe, chronic anorexia nervosa? Neuropsychiatry 1:467–476. https://doi.org/10.2217/npy.11.50

    Article  Google Scholar 

  70. Costa B, Comelli F, Bettoni I, Colleoni M, Giagnoni G (2008) The endogenous fatty acid amide, palmitoylethanolamide, has anti-allodynic and anti-hyperalgesic effects in a murine model of neuropathic pain: Involvement of CB1, TRPV1 and PPARγ receptors and neurotrophic factors. Pain 139:541–550. https://doi.org/10.1016/j.pain.2008.06.003

    Article  CAS  PubMed  Google Scholar 

  71. Hernández-Muñoz S, Camarena-Medellin B, González-Macías L, Aguilar-García A, Flores-Flores G, Luna Dominguez D, Azaola-Espinosa A, Flores-Ramos M, Caballero-Romo A (2020) Sequence analysis of five exons of SLC6A4 gene in Mexican patients with anorexia nervosa and bulimia nervosa. Gene 748:144675. https://doi.org/10.1016/j.gene.2020.144675

    Article  CAS  PubMed  Google Scholar 

  72. Strober M, Freeman R, Lampert C, Diamond J, Kaye W (2000) Controlled family study of anorexia nervosa and bulimia nervosa: evidence of shared liability and transmission of partial syndromes. Am J Psychiatry 157:393–401. https://doi.org/10.1176/appi.ajp.157.3.393

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We really appreciated the work and collaboration of the healthcare staff of Palazzo Francisci residence (Todi, Italy) during patient enrollment. The Authors are also grateful for the support of the Consorzio Interuniversitario per le Biotecnologie (CIB).

Funding

This research was funded by PROVINCIA AUTONOMA DI BOLZANO, grant number 222474/2021.

Author information

Author notes

  1. Maria Rachele Ceccarini and Vincenza Precone have contributed equally.

Authors and Affiliations

  1. Department of Pharmaceutical Sciences, University of Perugia, Perugia, Italy

    Maria Rachele Ceccarini & Tommaso Beccari

  2. C.I.B., Consorzio Interuniversitario per le Biotecnologie, Trieste, Italy

    Maria Rachele Ceccarini & Tommaso Beccari

  3. MAGI EUREGIO, Bolzano, Italy

    Vincenza Precone, Elena Manara, Kristjana Dhuli, Kevin Donato, Giuseppe Marceddu & Matteo Bertelli

  4. MAGI’S LAB, Rovereto, TN, Italy

    Stefano Paolacci, Paolo Enrico Maltese, Giulia Guerri & Matteo Bertelli

  5. Department of Eating Disorder, Palazzo Francisci Todi, USL 1 Umbria, Todi, PG, Italy

    Valentina Benfatti & Laura Dalla Ragione

  6. Dipartimento Universitario Scienze della Vita e Sanità Pubblica, Sezione di Medicina Genomica, Università Cattolica del Sacro Cuore, 00168, Rome, Italy

    Pietro Chiurazzi

  7. Fondazione Policlinico Universitario “A. Gemelli” IRCCS, UOC Genetica Medica, 00168, Roma, Italy

    Pietro Chiurazzi

  8. Food Science and Human Nutrition Unit, University Campus Biomedico of Rome, Rome, Italy

    Laura Dalla Ragione

Authors
  1. Maria Rachele Ceccarini
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Vincenza Precone
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Elena Manara
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Stefano Paolacci
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Paolo Enrico Maltese
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Valentina Benfatti
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Kristjana Dhuli
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Kevin Donato
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Giulia Guerri
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Giuseppe Marceddu
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Pietro Chiurazzi
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Laura Dalla Ragione
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Tommaso Beccari
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Matteo Bertelli
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conceptualization, MRC, TB, MB; methodology, GM and GG; software, GM; validation, EM, KD and GC; formal analysis, GM; investigation, EM, VB, SP, PEM, MRC, TB, LDR and MB; data curation, MRC; writing—original draft preparation, VP, MRC; writing—review and editing, EM, SP, MRC, TB, LDR and MB; supervision, TB, MB; project administration, MB; funding acquisition, MB. All authors have read and agreed to the published version of the manuscript.

Corresponding author

Correspondence to Maria Rachele Ceccarini.

Ethics declarations

Conflicts of interest

The authors declare no conflict of interest.

Ethics approval

The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Institutional Review Board Ethics Committee of Aziende Sanitarie (CEAS) della Regione Umbria (Prot. N. 29616/12/AV).

Consent to participate

Informed consent to participate was obtained from all subjects involved in the study.

Consent for publication

Informed consent for publication was obtained from all subjects involved in the study.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 54 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ceccarini, M., Precone, V., Manara, E. et al. A next generation sequencing gene panel for use in the diagnosis of anorexia nervosa. Eat Weight Disord 27, 1869–1880 (2022). https://doi.org/10.1007/s40519-021-01331-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40519-021-01331-0

Keywords

Search

Navigation