title: Linkage analysis of anorexia and bulimia nervosa cohorts using selected behavioral phenotypes as quantitative traits or covariates.
abstract: To increase the likelihood of finding genetic variation conferring liability to eating disorders, we measured over 100 attributes thought to be related to liability to eating disorders on affected individuals from multiplex families and two cohorts: one recruited through a proband with anorexia nervosa (AN; AN cohort); the other recruited through a proband with bulimia nervosa (BN; BN cohort). By a multilayer decision process based on expert evaluation and statistical analysis, six traits were selected for linkage analysis (1): obsessionality (OBS), age at menarche (MENAR), and anxiety (ANX) for quantitative trait locus (QTL) linkage analysis; and lifetime minimum body mass index (BMI), concern over mistakes (CM), and food-related obsessions (OBF) for covariate-based linkage analysis. The BN cohort produced the largest linkage signals: for QTL linkage analysis, four suggestive signals: (for MENAR, at 10p13; for ANX, at 1q31.1, 4q35.2, and 8q13.1); for covariate-based linkage analyses, both significant and suggestive linkages (for BMI, one significant [4q21.1] and three suggestive [3p23, 10p13, 5p15.3]; for CM, two significant [16p13.3, 14q21.1] and three suggestive [4p15.33, 8q11.23, 10p11.21]; and for OBF, one significant [14q21.1] and five suggestive [4p16.1, 10p13.1, 8q11.23, 16p13.3, 18p11.31]). Results from the AN cohort were far less compelling: for QTL linkage analysis, two suggestive signals (for OBS at 6q21 and for ANX at 9p21.3); for covariate-based linkage analysis, five suggestive signals (for BMI at 4q13.1, for CM at 11p11.2 and 17q25.1, and for OBF at 17q25.1 and 15q26.2). Overlap between the two cohorts was minimal for substantial linkage signals.
authors.affiliation: Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA 15213-2593, USA.
authors.forename: Silviu-Alin
authors.initials: SA
authors.lastname: Bacanu
authors.forename: Cynthia M
authors.initials: CM
authors.lastname: Bulik
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: Pamela
authors.initials: P
authors.lastname: Keel
authors.forename: Allan S
authors.initials: AS
authors.lastname: Kaplan
authors.forename: James E
authors.initials: JE
authors.lastname: Mitchell
authors.forename: Alessandro
authors.initials: A
authors.lastname: Rotondo
authors.forename: Michael
authors.initials: M
authors.lastname: Strober
authors.forename: Janet
authors.initials: J
authors.lastname: Treasure
authors.forename: D Blake
authors.initials: DB
authors.lastname: Woodside
authors.forename: Vibhor A
authors.initials: VA
authors.lastname: Sonpar
authors.forename: Weiting
authors.initials: W
authors.lastname: Xie
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Bergen
authors.forename: Wade H
authors.initials: WH
authors.lastname: Berrettini
authors.forename: Walter H
authors.initials: WH
authors.lastname: Kaye
authors.forename: Bernie
authors.initials: B
authors.lastname: Devlin
mesh_terms: D000856:Anorexia Nervosa / Q000235:genetics*; D001007:Anxiety / Q000235:genetics; D052018:Bulimia Nervosa / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D008572:Menarche / Q000235:genetics; D010641:Phenotype; D040641:Quantitative Trait Loci; D019655:Quantitative Trait, Heritable