title: Significant linkage on chromosome 10p in families with bulimia nervosa.
abstract: 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.
authors.affiliation: Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA 23298-0126, USA. cbulik@hsc.vcu.edu
authors.forename: Cynthia M
authors.initials: CM
authors.lastname: Bulik
authors.forename: B
authors.initials: B
authors.lastname: Devlin
authors.forename: Silviu-Alin
authors.initials: SA
authors.lastname: Bacanu
authors.forename: Laura
authors.initials: L
authors.lastname: Thornton
authors.forename: Kelly L
authors.initials: KL
authors.lastname: Klump
authors.forename: Manfred M
authors.initials: MM
authors.lastname: Fichter
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Halmi
authors.forename: Allan S
authors.initials: AS
authors.lastname: Kaplan
authors.forename: Michael
authors.initials: M
authors.lastname: Strober
authors.forename: D Blake
authors.initials: DB
authors.lastname: Woodside
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Bergen
authors.forename: J Kelly
authors.initials: JK
authors.lastname: Ganjei
authors.forename: Scott
authors.initials: S
authors.lastname: Crow
authors.forename: James
authors.initials: J
authors.lastname: Mitchell
authors.forename: Alessandro
authors.initials: A
authors.lastname: Rotondo
authors.forename: Mauro
authors.initials: M
authors.lastname: Mauri
authors.forename: Giovanni
authors.initials: G
authors.lastname: Cassano
authors.forename: Pamela
authors.initials: P
authors.lastname: Keel
authors.forename: Wade H
authors.initials: WH
authors.lastname: Berrettini
authors.forename: Walter H
authors.initials: WH
authors.lastname: Kaye
mesh_terms: D002032:Bulimia / Q000235:genetics*; D002874:Chromosome Mapping; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics*; D003198:Computer Simulation; D005260:Female; D008040:Genetic Linkage / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008126:Lod Score; D008297:Male; D035781:Siblings; D014839:Vomiting / Q000235:genetics