Bulimia nervosa (BN) is strongly familial, and additive genetic effects appear to contribute substantially to the observed familiality. In turn, behavioral components of BN, such as self-induced vomiting, are reliably measured and heritable. To identify regions of the genome harboring genetic variants conferring susceptibility to BN, we conducted a linkage analysis of multiplex families with eating disorders that were identified through a proband with BN. Linkage analysis of the entire sample of 308 families yielded a double peak, with the highest nonparametric multipoint maximum LOD score (MLS), of 2.92, on chromosome 10. Given the high heritability of self-induced vomiting and the reliability with which it can be measured, we performed linkage analysis in a subset (n = 133) of families in which at least two affected relatives reported a symptom pattern that included self-induced vomiting. The highest MLS (3.39) observed was on chromosome 10, between markers D10S1430 and D10S1423. These results provide evidence of the presence of a susceptibility locus for BN on chromosome 10p. Using simulations, we demonstrate that both of these scores, 2.92 and 3.39, meet the widely accepted criterion for genomewide significance. Another region on 14q meets the criterion for genomewide suggestive linkage, with MLSs of 1.97 (full sample) and 1.75 (subset) at 62 centimorgans from p-ter.
Bibliographical noteFunding Information:
The authors wish to thank the Price Foundation for the support of the clinical collection of subjects and genotyping and for contribution to the support of data analysis. Data analysis was also supported by National Institutes of Health grants MH57881 (to B.D.) and K01-MH01553 (to C.B.). Genotypic markers, allele frequencies, and genetic maps were generated at the Center for Medical Genetics, Marshfield Medical Research Foundation, with support from the National Heart, Lung and Blood Institute. Michael Mullokandov, Kevin Jacobs, and Meredith Yeager helped to prepare and manage these data. The authors are indebted to the participating families for their contribution of time and effort in support of this study.