Bulik Cynthia M, Bacanu Silviu-Alin, Klump Kelly L, Fichter Manfred M, Halmi Katherine A, Keel Pamela, Kaplan Allan S, Mitchell James E, Rotondo Alessandro, Strober Michael, Treasure Janet, Woodside D Blake, Sonpar Vibhor A, Xie Weiting, Bergen Andrew W, Berrettini Wade H, Kaye Walter H, Devlin Bernie
Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Am J Med Genet B Neuropsychiatr Genet. 2005 Nov 5;139B(1):81-7. doi: 10.1002/ajmg.b.30227.
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.
神经性厌食症（AN）和神经性贪食症（BN）的易感性源于遗传和环境因素的相互作用。为了探究遗传因素的作用，我们测量了通过一名神经性厌食症先证者纳入的154个多重家庭（AN队列）以及通过一名神经性贪食症先证者纳入的244个多重家庭（BN队列）中饮食失调个体的100多种精神、人格和气质表型。为了选择这些属性的简约子集进行连锁分析，我们基于专家评估和统计分析对变量进行了多层决策过程。性状选择的标准包括与饮食失调病理学的相关性、已发表的遗传力证据以及我们数据的结果。基于这些标准，我们选择了六个性状进行连锁分析。强迫观念、初潮年龄和综合焦虑量表显示出可遗传数量性状的特征，如正态分布和家族相关性，因此似乎非常适合进行数量性状基因座（QTL）连锁分析。相比之下，一些家庭在三个变量上表现出高度一致和极端的值，即终生最低体重指数（疾病过程中达到的最低BMI）、对错误的担忧以及与食物相关的强迫观念，而其他家庭则没有。这些分布与混合人群一致，因此这些变量与协变量连锁分析相匹配。连锁结果将在后续报告中呈现。我们的报告为利用丰富的表型进行遗传分析制定了一个系统路线图，包括选择与这些表型相匹配的连锁方法。
