1. ¹Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA (current affiliation)
2. ²Core Genotyping Facility, Advanced Technology Center, National Cancer Institute, Gaithersburg, MD, USA
3. ³TissueGene, Inc., Gaithersburg, MD, USA
4. ⁴Department of Psychological Medicine, Cardiff University, Cardiff, UK
5. ⁵Laboratory of Human Cytogenetics, Cancer Research UK, London, UK
6. ⁶Laboratorio di Biologia Cellulare e dello Sviluppo, University of Pisa, La Fontina Ghezzano, Pisa, Italy
7. ⁷Klinik Roseneck, Hospital for Behavioral Medicine, Affiliated with University of Munich, Prien, Germany
8. ⁸New York Presbyterian Hospital-Westchester, Weill Medical College of Cornell University, White Plains, NY, USA
9. ⁹Department of Psychiatry, University Health Network, Toronto General Hospital, Toronto, ON, Canada
10. ¹⁰Neuropsychiatric Institute and Hospital, School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA
11. ¹¹Institute of Psychiatry, Kings College, London, England, UK
12. ¹²Department of Psychiatry, University of North Carolina, Chapel Hill, NC, USA
13. ¹³Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
14. ¹⁴Center for Neurobiology and Behavior, Department of Psychiatry, University of Pennsylvania Health System, Clinical Research Building, Philadelphia, PA, USA
15. ¹⁵Laboratory of Neurogenetics, National Institute of Alcohol Abuse and Alcoholism, Rockville, MD, USA

Correspondence: Dr AW Bergen, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Boulevard, Bethesda, MD 20892-7236, USA. Tel: +1 301 435 7614; Fax: +1 301 402 4489; E-mail: bergena@mail.nih.gov

¹⁶This research originated in part through the Price Foundation Collaboration and does not represent the opinion of the NIH, the DHHS or the Federal Government.

Received 18 August 2003; Revised 31 January 2005; Accepted 7 February 2005; Published online 25 May 2005.

Abstract

To investigate whether the dopaminergic system plays a role in the etiology of anorexia nervosa (AN) via the dopamine D2 receptor, we investigated association and transmission disequilibrium at seven single-nucleotide polymorphisms (SNPs) spanning about 75 kbp of the gene DRD2. We studied 191 probands with a DSM-IV diagnosis of AN, 457 parents and affected relatives with a DSM-IV eating disorder diagnosis, and 98 unrelated, female, normal weight controls. The -141 C/- insertion/deletion (-141 Indel), previously shown to affect DRD2 transcription efficiency, and multiple exon seven polymorphisms, one of which has previously been shown to affect DRD2 transcript stability, exhibited statistically significant association with diagnosis in haplotype transmission disequilibrium and in haplotype case : control analyses. Significant linkage disequilibrium between the -141 Indel and two exon seven SNPs (939Y and 957Y) was observed over a distance of >50 kbp in the AN probands but not in the controls. Genetically transmitted variation in D2 dopamine receptor expression mediated by functional polymorphisms affecting transcription and translation efficiency may play a role in vulnerability to AN.