Anorexia nervosa (AN) is a chronic and often fatal disorder that affects 0.3% of women. There is no FDA-approved treatment, and the mortality rate is 5% per decade. In addition to environmental influence, family and twin studies demonstrate substantial heritability for AN. Because the etiology of this devastating illness is not known, we undertook a pilot study to examine its genetic underpinnings. With the support of a private foundation, our multicenter collaboration has collected 196 multiplex AN kindreds from 7 sites across North America and Europe. With a limited sample, this pilot study has produced four suggestive linkages from a genome-wide scan, one very close to genome-wide significance (Chromosome 1 at 70 cM, p - 0.0001; Chr. 1 at 202 cM, LOD = 3 46. p = 0.00003; Chr. 2 at 102 cM, LOD = 2.22: p = 0.00070; and Chr. 13 at 102 cM. LOD = 2.50; p = 0.00035) The first suggestive linkage results from a subset of the sample, namely individuals with the restricting subtype of AN. The other results were obtained by incorporating two covariates, drive-for-thinness from the Eating Disorders lnventory-2 and the total score from the Yale-Brown Obsessive Compulsive Scale, into covariate-based linkage analysis. Based on these very promising linkage findings, we believe genes underlying liability to AN can be mapped by augmenting the pilot sample. Thus support is requested for a multicenter effort to collect 400 affected relative pairs with AN. Over a five year period, the 11 collaborating groups (10 clinical, 1 analytic) will collect diagnostic and other phenotypic data and blood samples from 400 multiplex AN kindreds. The UNIVERSITY OF PITTSBURGH is one of these research groups. each of which is submitting a nearly identical application as a group of collaborating ROls. Microsatellites will be genotyped at H 10 cM intervals across the genome using all new families. Linkage analyses will be conducted by using diagnostic and phenotypic data to confirm suggestive linkages from the pilot study and to identify new genomic regions of interest. The diagnostic and genetic data and lymphoblastoid cell lines (derived from blood samples) will become part of a national archival resource for genetic studies of AN through the NIMH Genetics Initiative.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
1R01MH066288-01
Application #
6531456
Study Section
Special Emphasis Panel (ZRG1-MGN (02))
Program Officer
Moldin, Steven Owen
Project Start
2002-09-03
Project End
2006-07-31
Budget Start
2002-09-03
Budget End
2003-07-31
Support Year
1
Fiscal Year
2002
Total Cost
$228,750
Indirect Cost
Name
University of California Los Angeles
Department
Psychiatry
Type
Schools of Medicine
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Clarke, Toni-Kim; Crist, Richard C; Doyle, Glenn A et al. (2014) Characterization of genetic variation in the VGLL4 gene in anorexia nervosa. Psychiatr Genet 24:183-4
Boraska, V; Franklin, C S; Floyd, J A B et al. (2014) A genome-wide association study of anorexia nervosa. Mol Psychiatry 19:1085-94
Selby, Edward A; Bulik, Cynthia M; Thornton, Laura et al. (2010) Refining behavioral dysregulation in borderline personality disorder using a sample of women with anorexia nervosa. Personal Disord 1:250-7
Selby, Edward A; Smith, April R; Bulik, Cynthia M et al. (2010) Habitual starvation and provocative behaviors: two potential routes to extreme suicidal behavior in anorexia nervosa. Behav Res Ther 48:634-45
Kaye, Walter H; Bulik, Cynthia M; Plotnicov, Katherine et al. (2008) The genetics of anorexia nervosa collaborative study: methods and sample description. Int J Eat Disord 41:289-300