Significant linkage on chromosome 10p in families with bulimia nervosa.
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.
Bulik
Cynthia M
CM
Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA 23298-0126, USA. cbulik@hsc.vcu.edu
Devlin
B
B
Bacanu
Silviu-Alin
SA
Thornton
Laura
L
Klump
Kelly L
KL
Fichter
Manfred M
MM
Halmi
Katherine A
KA
Kaplan
Allan S
AS
Strober
Michael
M
Woodside
D Blake
DB
Bergen
Andrew W
AW
Ganjei
J Kelly
JK
Crow
Scott
S
Mitchell
James
J
Rotondo
Alessandro
A
Mauri
Mauro
M
Cassano
Giovanni
G
Keel
Pamela
P
Berrettini
Wade H
WH
Kaye
Walter H
WH
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