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Genetics in Eating Disorders: State of the Science

Published online by Cambridge University Press:  07 November 2014

Cynthia M. Bulik  and
Federica Tozzi
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Abstract

Eating disorders have been viewed as psychiatric illnesses that are strongly influenced by societal pressures towards thinness and attractiveness. Although the environmental context of these disorders must not be neglected, recent research in the area of genetic epidemiology suggests a substantial influence of genetic factors on liability to eating disorders. This review presents a synthesis of current knowledge about genetic factors implicated in the etiology of eating disorders.

Type
Review Articles
Information
CNS Spectrums , Volume 9 , Issue 7 , July 2004 , pp. 511 - 515
Copyright
Copyright © Cambridge University Press 2004

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References

REFERENCES

1.Lilenfeld, LR, Kaye, WH, Greeno, CG, et al.A controlled family study of anorexia nervosa and bulimia nervosa: psychiatric disorders in first-degree relatives and effects of proband comorbidity. Arch Gen Psychiatry. 1998;55:603–610.CrossRefGoogle ScholarPubMed
2.Strober, M, Freeman, R, Lampert, C, Diamond, J, Kaye, W. Controlled family study of anorexia nervosa and bulimia nervosa: evidence of shared liability and transmission of partial syndromes. Am J Psychiatry. 2000;157:393–401.CrossRefGoogle ScholarPubMed
3.Bulik, CM, Sullivan, PF, Wade, TD, Kendler, KS. Twin studies of eating disorders: a review. Int J Eat Disord. 2000;27:1–20.3.0.CO;2-Q>CrossRefGoogle ScholarPubMed
4.Kendler, KS, MacLean, C, Neale, M, Kessler, R, Heath, A, Eaves, L. The genetic epidemiology of bulimia nervosa. Am J Psychiatry. 1991;148:1627–1637.Google ScholarPubMed
5.Wade, T, Martin, NG, Neale, MC, et al.The structure of genetic and environmental risk factors for three measures of disordered eating. Psychol Med. 1999;29:925–934.CrossRefGoogle ScholarPubMed
6.Wade, TD, Bulik, CM, Neale, M, Kendler, KS. anorexia nervosa and major depression: shared genetic and environmental risk factors. Am J Psychiatry. 2000;157:469–471.CrossRefGoogle ScholarPubMed
7.Hudson, JI, Pope, HG Jr, Jonas, JM, Yurgelun-Todd, D, Frankenburg, FR. A controlled family history study of bulimia. Psychol Med. 1987;17:883–890.CrossRefGoogle ScholarPubMed
8.Mangweth, B, Hudson, JI, Pope, HG, et al.Family study of the aggregation of eating disorders and mood disorders. Psychol Med. 2003;33:1319–1323.CrossRefGoogle ScholarPubMed
9.Gershon, E, Schreiber, J, Hamovit, J, et al.Anorexia nervosa and major affective disorders associated in families: a preliminary report. In: Guze, SB, Earls, FJ, Barrett, JE, eds. Childhood Psychopathobgy and Development. New York, NY: Raven Press; 1983:279–284.Google Scholar
10.Walters, EE, Kendler, KS. anorexia nervosa and anorexic-like syndromes in a population-based female twin sample. Am J Psychiatry. 1995;152:64–71.Google Scholar
11.Sham, P. Statistics in Human Genetics. London, England: Arnold; 1998.Google Scholar
12.Sasieni, PD. From genotypes to genes: doubling the sample size. Biometrics. 1997;53:1253–1261.CrossRefGoogle ScholarPubMed
13.Kidd, KK. Associations of disease with genetic markers: deja vu all over again. Am J Med Genet. 1993;48:71–73.CrossRefGoogle Scholar
14.Allison, DB, Heo, M, Schork, NJ, Wong, SL, Elston, RC. Extreme selection strategies in gene mapping studies of oligogenic quantitative traits do not always increase power. Hum Hered. 1998;48:97–107.CrossRefGoogle Scholar
15.Merikangas, KR, Chakravarti, A, Moldin, SO, et al.Future of genetics of mood disorders research. Biol Psychiatry. 2002;52:457–477.CrossRefGoogle ScholarPubMed
16.Risch, N, Merikangas, K. Linkage studies of psychiatric disorders. Eur Arch Psychiatry Clin Neurosci. 1993;243:143–149.CrossRefGoogle ScholarPubMed
17.Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Washington, DC: American Psychiatric Press; 1994.Google Scholar
18.Blundell, JE, Lawton, CL, Halford, JC. Serotonin, eating behavior, and fat intake. Obes Res. 1995;3(suppl 4):471S–476S.CrossRefGoogle ScholarPubMed
19.Brewerton, TD. Toward a unified theory of serotonin dysregulation in eating and related disorders. Psychoneuroendocrinology. 1995;20:561–590.CrossRefGoogle Scholar
20.Brewerton, TD, Jimerson, DC. Studies of serotonin function in anorexia nervosa. Psychiatry Res. 1996;62:31–42.CrossRefGoogle ScholarPubMed
21.Jimerson, DC, Lesem, MD, Kaye, WH, Brewerton, TD. Low serotonin and dopamine metabolite concentrations in cerebrospinal fluid from bulimic patients with frequent binge episodes. Arch Gen Psychiatry. 1992;49:132–138.CrossRefGoogle ScholarPubMed
22.Kaye, WH, Gwirtsman, HE, George, DT, Ebert, MH. Altered serotonin activity in anorexia nervosa after long-term weight restoration. Does elevated cerebrospinal fluid 5-hydroxyindoleacetic acid level correlate with rigid and obsessive behavior? Am J Psychiatry. 1991;48:556–562.Google ScholarPubMed
23.Kaye, WH, Greeno, CG, Moss, H, et al.Altered serotonin activity and psychiatric symptoms after recovery from bulimia nervosa. Am J Psychiatry. 1998;55:927–935.Google ScholarPubMed
24.Collier, DA, Arranz, MJ, Li, T, Mupita, D, Brown, N, Treasure, J. Association between 5-HT2A gene promoter polymorphism and anorexia nervosa. Lancet. 1997;350:412.CrossRefGoogle ScholarPubMed
25.Enoch, MA, Kaye, WH, Rotondo, A, Greenberg, BD, Murphy, DL, Goldman, D. 5-HT2A promoter polymorphism -1438G/A, anorexia nervosa, and obsessive-compulsive disorder. Lancet. 1998;351:1785–1786.CrossRefGoogle ScholarPubMed
26.Nacmias, B, Ricca, V, Tedde, A, Mezzani, B, Rotella, CM, Sorbi, S. 5-HT2A receptor gene polymorphisms in anorexia nervosa and bulimia nervosa. Neurosci Lett. 1999;277:134–136.CrossRefGoogle ScholarPubMed
27.Ricca, V, Nacmias, B, Cellini, E, Di Bernardo, M, Rotella, CM, Sorbi, S. 5-HT2A receptor gene polymorphism and eating disorders. Neurosci Lett. 2002;323:105–108.CrossRefGoogle ScholarPubMed
28.Sorbi, S, Nacmias, B, Tedde, A, Ricca, V, Mezzani, B, Rotella, CM. 5-HT2A promoter polymorphism in anorexia nervosa. Lancet. 1998;351:1785.CrossRefGoogle ScholarPubMed
29.Hu, X, Giotakis, O, Li, T, Karwautz, A, Treasure, J, Collier, DA. Association of the 5-HT2c gene with susceptibility and minimum body mass index in anorexia nervosa. Neuroreport. 2003;14:781–783.CrossRefGoogle ScholarPubMed
30.Westberg, L, Bah, J, Rastam, M, et al.Association between a polymorphism of the 5-HT2C receptor and weight loss in teenage girls. Neuropsychopharmacology. 2002;26:789–793.CrossRefGoogle ScholarPubMed
31.Di Bella, DD, Catalano, M, Cavallini, MC, Riboldi, C, Bellodi, L. Serotonin transporter linked polymorphic region in anorexia nervosa and bulimia nervosa. Mol Psychiatry. 2000;5:233–234.CrossRefGoogle ScholarPubMed
32.Fumeron, F, Betoulle, D, Aubert, R, et al.Association of a functional 5-HT transporter gene polymorphism with anorexia nervosa and food intake. Mol Psychiatry. 2001;6:9–10.CrossRefGoogle ScholarPubMed
33.Ando, T, Komaki, G, Karibe, M, et al.5-HT2A promoter polymorphism is not associated with anorexia nervosa in Japanese patients. Psychiatr Genet. 2001;11:157–160.CrossRefGoogle Scholar
34.Campbell, DA, Sundaramurthy, D, Markham, AF, et al.Lack of association between 5-HT2A gene promoter polymorphism and susceptibility to anorexia nervosa [letter]. Lancet. 1998;351:499.CrossRefGoogle ScholarPubMed
35.Gorwood, P, Ades, J, Bellodi, L, et al.The 5-HT(2A) -1438G/A polymorphism in anorexia nervosa: a combined analysis of 316 trios from six European centres. Mol Psychiatry. 2002;7:90–94.CrossRefGoogle ScholarPubMed
36.Hinney, A, Ziegler, A, Nothen, MM, Remschmidt, H, Hebebrand, J. 5-HT2A receptor gene polymorphisms, anorexia nervosa, and obesity. Lancet. 1997;350:1324–1325.CrossRefGoogle ScholarPubMed
37.Karwautz, A, Rabe-Hesketh, S, Hu, X, et al.Individual-specific risk factors for anorexia nervosa: a pilot study using a discordant sister-pair design. Psychol Med. 2001;31:317–329.CrossRefGoogle ScholarPubMed
38.Nishiguchi, N, Matsushita, S, Suzuki, K, Murayama, M, Shirakawa, O, Higuchi, S. Association between 5HT2A receptor gene promoter region polymorphism and eating disorders in Japanese patients. Biol Psychiatry. 2001;50:123–128.CrossRefGoogle ScholarPubMed
39.Ziegler, A, Hebebrand, J, Gorg, T, et al.Further lack of association between the 5-HT2A gene promoter polymorphism and susceptibility to eating disorders and a meta-analysis pertaining to anorexia nervosa. Mol Psychiatry. 1999;4:410–412.CrossRefGoogle Scholar
40.Burnet, PW, Smith, KA, Cowen, PJ, Fairburn, CG, Harrison, PJ. Allelic variation of the 5-HT2C receptor (HTR2C) in bulimia nervosa and binge eating disorder. Psychiatr Genet. 1999;9:101–104.CrossRefGoogle ScholarPubMed
41.Hinney, A, Barth, N, Ziegler, A, et al.Serotonin transporter gene-linked polymorphic region: allele distributions in relationship to body weight and in anorexia nervosa. Life Sci. 1997;61:295–303.CrossRefGoogle ScholarPubMed
42.Sundaramurthy, D, Pieri, LF, Gape, H, Markham, AF, Campbell, DA. Analysis of the serotonin transporter gene linked polymorphism (5-HTTLPR) in anorexia nervosa. Am J Med Genet. 2000;96:53–55.3.0.CO;2-X>CrossRefGoogle ScholarPubMed
43.Urwin, RE, Bennetts, BH, Wilcken, B, Beumont, PJ, Russell, JD, Nunn, KP. Investigation of epistasis between the serotonin transporter and norepinephrine transporter genes in anorexia nervosa. Neuropsychopharmacology. 2003;28:1351–1355.CrossRefGoogle ScholarPubMed
44.Han, L, Nielsen, DA, Rosenthal, NE, et al.No coding variant of the tryptophan hydroxylase gene detected in seasonal affective disorder, obsessive-compulsive disorder, anorexia nervosa, and alcoholism. Biol Psychiatry. 1999;45:615–619.CrossRefGoogle ScholarPubMed
45.Hinney, A, Herrmann, H, Lohr, T, et al.No evidence for an involvement of alleles of polymorphisms in the serotonin1Dbeta and 7 receptor genes in obesity, underweight or anorexia nervosa. Int J Obes Relat Metab Disord. 1999;23:760–763.CrossRefGoogle ScholarPubMed
46.Levitan, RD, Kaplan, AS, Masellis, M, et al.Polymorphism of the serotonin 5-HT1B receptor gene (HTR1B) associated with minimum lifetime body mass index in women with bulimia nervosa. Biol Psychiatry. 2001;50:640–643.CrossRefGoogle ScholarPubMed
47.Kaye, WH, Frank, GK, and McConaha, C. Altered dopamine activity after recovery from restricting-type anorexia aervosa. Neuropsychopharmacology. 1999;21:503–506.CrossRefGoogle Scholar
48.Pirke, KM. Central and peripheral noradrenalin regulation in eating disorders. Psychiatry Res. 1996;62:43–49.CrossRefGoogle ScholarPubMed
49.Bruins-Slot, L, Gorwood, P, Bouvard, M, et al.Lack of association between anorexia nervosa and D3 dopamine receptor gene. Biol Psychiatry. 1998;43:76–78.CrossRefGoogle ScholarPubMed
50.Hinney, A, Schneider, J, Ziegler, A, et al.No evidence for involvement of polymorphisms of the dopamine D4 receptor gene in anorexia nervosa, underweight, and obesity. Am J Med Genet. 1999;88:594–597.3.0.CO;2-F>CrossRefGoogle ScholarPubMed
51.Hinney, A, Lentes, KU, Rosenkranz, K, et al.Beta 3-adrenergic-receptor allele distributions in children, adolescents and young adults with obesity, underweight or anorexia nervosa. Int J Obes Relat Metab Disord. 1997;21:224–230.CrossRefGoogle ScholarPubMed
52.Frisch, A, Laufer, N, Danziger, Y, et al.Association of anorexia nervosa with the high activity allele of the COMT gene: a family-based study in Israeli patients. Mol Psychiatry. 2001;6:243–245.CrossRefGoogle ScholarPubMed
53.Urwin, RE, Bennetts, B, Wilcken, B, et al.anorexia nervosa (restrictive subtype) is associated with a polymorphism in the novel norepinephrine transporter gene promoter polymorphic region. Mol Psychiatry. 2002;7:52–657.CrossRefGoogle ScholarPubMed
54.Urwin, RE, Bennetts, BH, Wilcken, B, et al.Gene-gene interaction between the monoamine oxidase A gene and solute carrier family 6 (neurotransmitter transporter, noradrenalin) member 2 gene in anorexia netvosa (restrictive subtype). Eur J Hum Genet. 2003;11:945–950.CrossRefGoogle Scholar
55.Vink, T, Hinney, A, van Elburg, AA, et al.Association between an agoutirelated protein gene polymorphism and anorexia nervosa. Mol Psychiatry. 2001;6:325–328.CrossRefGoogle ScholarPubMed
56.Campbell, DA, Sundaramurthy, D, Gordon, D, Markham, AF, Pieri, LF. Association between a marker in the UCP-2/UCP-3 gene cluster and genetic susceptibility to anorexia nervosa. Mol Psychiatry. 1999;4:68–70.CrossRefGoogle ScholarPubMed
57.Hu, X, Murphy, F, Karwautz, A, et al.Analysis of microsatellite markers at the UCP2/UCP3 locus on chromosome 11q13 in anorexia nervosa. Mol Psychiatry. 2002;7:276–277.CrossRefGoogle ScholarPubMed
58.Eastwood, H, Brown, KM, Markovic, D, et al.Variation in the ESR1 and ESR2 Genes and Genetic Susceptibility to anorexia nervosa. Mol Psychiatry. 2002;7:86–89.CrossRefGoogle ScholarPubMed
59.Rosenkranz, K, Hinney, A, Ziegler, A, et al.Systematic mutation screening of the estrogen receptor beta gene in probands of different weight extremes: identification of several genetic variants. J Clin Endocrinol Metab. 1998;83:4524–4527.CrossRefGoogle ScholarPubMed
60.Hinney, A, Bornscheuer, A, Depenbusch, M, et al.No evidence for involvement of the leptin gene in anorexia nervosa, bulimia nervosa, underweight or early onset extreme obesity: identification of two novel mutations in the coding sequence and a novel polymorphism in the leptin gene linked upstream region. Mol Psychiatry. 1998;3:539–543.CrossRefGoogle ScholarPubMed
61.Hinney, A, Becker, I, Heibult, O, et al.Systematic mutation screening of the estrogen receptor beta gene in probands of different weight exttemes: identification of several genetic variants. Clin Endocrinol Metab. 1998;83:3737–3741.CrossRefGoogle Scholar
62.Hinney, A, Schmidt, A, Nottebom, K, et al.Several mutations in the melanocortin-4 receptor gene including a nonsense and a frameshift mutation associated with dominantly inherited obesity in humans J Clin Endocrinol Metab. 1999;84:1483–1486.CrossRefGoogle Scholar
63.Rosenkranz, K, Hinney, A, Ziegler, A, et al.Screening for mutations in the neuropeptide Y Y5 receptor gene in cohorts belonging to different weight extremes. Int J Obes Relat Metab Disord. 1998;22:157–163.CrossRefGoogle ScholarPubMed
64.Koronyo-Hamaoui, M, Danziger, Y, Frisch, A, et al.Association between anorexia nervosa and the hsKCa3 gene: a family-based and case control study. Mol Psychiatry. 2002;7:82–85.CrossRefGoogle ScholarPubMed
65.Ribases, M, Gratacos, M, Armengol, L, et al.Met66 in the brain-derived neurotrophic factor (BDNF) precursor is associated with anorexia nervosa restrictive type. Mol Psychiatry. 2003;8:745–751.CrossRefGoogle ScholarPubMed
66.Kaye, WH, Lilenfeld, LR, Berrettini, WH, et al.A search for susceptibility loci for anorexia nervosa: methods and sample description. Biol Psychiatry. 2000;47:794–803.CrossRefGoogle ScholarPubMed
67.Grice, DE, Halmi, KA, Fichter, MM, et al.Evidence for a susceptibility gene for anorexia nervosa on chromosome 1. Am J Hum Genet. 2002;70:787–792.CrossRefGoogle ScholarPubMed
68.Devlin, B, Bacanu, SA, Klump, KL, et al.Linkage analysis of anorexia nervosa incorporating behavioral covariates. Hum Mol Genet. 2002;11:689–696.CrossRefGoogle ScholarPubMed
69.Bulik, CM, Devlin, B, Bacanu, SA, et al.Significant linkage on chromosome 10p in families with bulimia nervosa. Am J Hum Genet. 2003;72:200–207.CrossRefGoogle ScholarPubMed
70.Sullivan, PF, Bulik, CM, and Kendler, KS. Genetic epidemiology of hinging and vomiting. Br J Psychiatry. 1998;173:75–79.CrossRefGoogle Scholar
71.Bergen, AW, van den Bree, MB, Yeager, M, et al.Candidate genes for anorexia nervosa in the 1p33-36 linkage region: serotonin 1D and delta opioid receptor loci exhibit significant association to anorexia nervosa. Mol Psychiatry. 2003;8:397–406.CrossRefGoogle ScholarPubMed
72.Caspi, A, Sugden, K, Moffitt, TE, et al.Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science. 2003;301:386–389.CrossRefGoogle ScholarPubMed