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 R01s. 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.
| Baker, Jessica H; Sisk, Cheryl L; Thornton, Laura M et al. (2014) Primary amenorrhea in anorexia nervosa: impact on characteristic masculine and feminine traits. Eur Eat Disord Rev 22:32-8 |
| 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 |
| Zerwas, Stephanie; Lund, Brian C; Von Holle, Ann et al. (2013) Factors associated with recovery from anorexia nervosa. J Psychiatr Res 47:972-9 |
| Baker, Jessica H; Thornton, Laura M; Strober, Michael et al. (2013) Temporal sequence of comorbid alcohol use disorder and anorexia nervosa. Addict Behav 38:1704-9 |
| Dellava, Jocilyn E; Trace, Sara E; Strober, Michael et al. (2012) Retrospective maternal report of early eating behaviours in anorexia nervosa. Eur Eat Disord Rev 20:111-5 |
| Hoffman, Elizabeth R; Gagne, Danielle A; Thornton, Laura M et al. (2012) Understanding the association of impulsivity, obsessions, and compulsions with binge eating and purging behaviours in anorexia nervosa. Eur Eat Disord Rev 20:e129-36 |
| Zucker, Nancy; Von Holle, Ann; Thornton, Laura M et al. (2011) The significance of repetitive hair-pulling behaviors in eating disorders. J Clin Psychol 67:391-403 |
| Root, Tammy L; Szatkiewicz, Jin P; Jonassaint, Charles R et al. (2011) Association of candidate genes with phenotypic traits relevant to anorexia nervosa. Eur Eat Disord Rev 19:487-93 |
| Reyes-Rodriguez, Mae Lynn; Von Holle, Ann; Ulman, Teresa Frances et al. (2011) Posttraumatic stress disorder in anorexia nervosa. Psychosom Med 73:491-7 |
Showing the most recent 10 out of 33 publications
