Linkage analysis of anorexia nervosa incorporating behavioral covariates
Linkage analysis of anorexia nervosa incorporating behavioral covariates
复制标题
DOI：
10.1093/hmg/11.6.689
复制
发表时间：
2002-03-15
影响因子：
3.5
通讯作者：
Kaye, WH
中科院分区：
文献类型：
--
作者：
Devlin, B;Bacanu, SA;Kaye, WH
饮食失调，例如神经性厌食症（AN）和神经性贪食症（BN），有遗传和环境基础。为了探索遗传因素对 AN 的影响，我们测量了来自 196 个多重家庭的被诊断患有饮食失调的个体的精神、性格和气质表型（全部通过 AN 先证者获得），并对分布在基因组中的 387 个短串联重复 (STR) 标记进行了基因分型。我们使用一种包含协变量的新方法对这些数据进行了多点受影响的兄弟对 (ASP) 连锁分析。通过探索饮食失调患者的七个典型特征，我们确定了两个变量：渴望瘦身和痴迷，这两个变量界定了 ASP 的人群。对于这两个特征或协变量，有一组 ASP 对这些特征具有较高且一致的值，这符合我们对 AN 患者的期望，而其他 ASP 簇则没有达到这些期望。当我们将这些协变量联合或单独纳入 ASP 连锁分析时，我们发现了几个暗示连锁的区域：一个接近全基因组显着性的区域位于 1 号染色体上（210 cM，D1S1660；LOD = 3.46，P = 0.00003），另一个位于 2 号染色体上（114 cM，D2S1790；LOD = 2.22，P = 0.00070）和 13 号染色体上的第三个区域（26 cM，D13S894；LOD = 2.50，P = 0.00035）。通过将我们的结果与使用更标准的连锁方法实现的结果进行比较，我们发现协变量为连锁分析传达了大量信息。
Eating disorders, such as anorexia nervosa (AN) and bulimia nervosa (BN), have genetic and environmental underpinnings. To explore genetic contributions to AN, we measured psychiatric, personality and temperament phenotypes of individuals diagnosed with eating disorders from 196 multiplex families, all accessed through an AN proband, as well as genotyping a battery of 387 short tandem repeat (STR) markers distributed across the genome. On these data we performed a multipoint affected sibling pair (ASP) linkage analysis using a novel method that incorporates covariates. By exploring seven attributes thought to typify individuals with eating disorders, we identified two variables, drive-for-thinness and obsessionality, which delimit populations among the ASPs. For both of these traits, or covariates, there were a cluster of ASPs who have high and concordant values for these traits, in keeping with our expectations for individuals with AN, and other clusters of ASPs who did not meet those expectations. When we incorporated these covariates into the ASP linkage analysis, both jointly and separately, we found several regions of suggestive linkage: one close to genome-wide significance on chromosome 1 (at 210 cM, D1S1660; LOD = 3.46, P = 0.00003), another on chromosome 2 (at 114 cM, D2S1790; LOD = 2.22, P = 0.00070) and a third region on chromosome 13 (at 26 cM, D13S894; LOD = 2.50, P = 0.00035). By comparing our results to those implemented using more standard linkage methods, we find the covariates convey substantial information for the linkage analysis.