title: Selection of eating-disorder phenotypes for linkage analysis.
abstract: Vulnerability to anorexia nervosa (AN) and bulimia nervosa (BN) arise from the interplay of genetic and environmental factors. To explore the genetic contribution, we measured over 100 psychiatric, personality, and temperament phenotypes of individuals with eating disorders from 154 multiplex families accessed through an AN proband (AN cohort) and 244 multiplex families accessed through a BN proband (BN cohort). To select a parsimonious subset of these attributes for linkage analysis, we subjected the variables to a multilayer decision process based on expert evaluation and statistical analysis. Criteria for trait choice included relevance to eating disorders pathology, published evidence for heritability, and results from our data. Based on these criteria, we chose six traits to analyze for linkage. Obsessionality, Age-at-Menarche, and a composite Anxiety measure displayed features of heritable quantitative traits, such as normal distribution and familial correlation, and thus appeared ideal for quantitative trait locus (QTL) linkage analysis. By contrast, some families showed highly concordant and extreme values for three variables-lifetime minimum Body Mass Index (lowest BMI attained during the course of illness), concern over mistakes, and food-related obsessions-whereas others did not. These distributions are consistent with a mixture of populations, and thus the variables were matched with covariate linkage analysis. Linkage results appear in a subsequent report. Our report lays out a systematic roadmap for utilizing a rich set of phenotypes for genetic analyses, including the selection of linkage methods paired to those phenotypes.
authors.affiliation: Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Cynthia M
authors.initials: CM
authors.lastname: Bulik
authors.forename: Silviu-Alin
authors.initials: SA
authors.lastname: Bacanu
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: D000465:Algorithms; D001068:Feeding and Eating Disorders / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008572:Menarche / Q000235:genetics; D015999:Multivariate Analysis; D010641:Phenotype; D040641:Quantitative Trait Loci