Genetics of Anorexia Nervosa

神经性厌食症的遗传学

基本信息

批准号：
6948247
负责人：
HARRY A BRANDT
金额：
$ 22.8万
依托单位：
SHEPPARD AND ENOCH PRATT HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2002
资助国家：
美国
起止时间：
2002-09-06 至 2007-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6948247
关键词：
anorexia nervosa anxiety cell line clinical research depression family genetics gene expression genetic screening genetic susceptibility genotype human subject interview linkage mapping mental disorder diagnosis obsessive compulsive disorder perception disorder personality

项目摘要

DESCRIPTION (provided by applicant): Anorexia nervosa (AN) is a chronic and often fatal disorder that affects 0.3% of women. There is no FDA-approved treatment, and the mortality rate is 5% per decade. In addition to environmental influence, family and twin studies demonstrate substantial heritability for AN. Because the etiology of this devastating illness is not known, we undertook a pilot study to examine its genetic underpinnings. With the support of a private foundation, our multicenter collaboration has collected 196 multiplex AN kindreds from 7 sites across North America and Europe. With a limited sample, this pilot study has produced four suggestive linkages from a genome-wide scan, one very close to genome-wide significance (Chromosome 1 at 70 cM, p - 0.0001; Chr. 1 at 202 cM, LOD = 3 46. p = 0.00003; Chr. 2 at 102 cM, LOD = 2.22: p = 0.00070; and Chr. 13 at 102 cM. LOD = 2.50; p = 0.00035) The first suggestive linkage results from a subset of the sample, namely individuals with the restricting subtype of AN. The other results were obtained by incorporating two covariates, drive-for-thinness from the Eating Disorders lnventory-2 and the total score from the Yale-Brown Obsessive Compulsive Scale, into covariate-based linkage analysis. Based on these very promising linkage findings, we believe genes underlying liability to AN can be mapped by augmenting the pilot sample. Thus support is requested for a multicenter effort to collect 400 affected relative pairs with AN. Over a five year period, the 11 collaborating groups (10 clinical, 1 analytic) will collect diagnostic and other phenotypic data and blood samples from 400 multiplex AN kindreds. The UNIVERSITY OF PITTSBURGH is one of these research groups. each of which is submitting a nearly identical application as a group of collaborating ROls. Microsatellites will be genotyped at H 10 cM intervals across the genome using all new families. Linkage analyses will be conducted by using diagnostic and phenotypic data to confirm suggestive linkages from the pilot study and to identify new genomic regions of interest. The diagnostic and genetic data and lymphoblastoid cell lines (derived from blood samples) will become part of a national archival resource for genetic studies of AN through the NIMH Genetics Initiative.

描述（由申请人提供）：神经性厌食症 (AN) 是一种慢性且常常致命的疾病，影响 0.3% 的女性。目前尚无 FDA 批准的治疗方法，死亡率为每十年 5%。除了环境影响之外，家庭和双胞胎研究还表明 AN 具有显着的遗传性。由于这种毁灭性疾病的病因尚不清楚，我们进行了一项试点研究来检查其遗传基础。在私人基金会的支持下，我们的多中心合作已从北美和欧洲的 7 个地点收集了 196 个多重 AN 亲属。这项试点研究利用有限的样本，从全基因组扫描中得出了四种提示性联系，其中一种非常接近全基因组显着性（1 号染色体在 70 cM，p - 0.0001；1 号染色体在 202 cM，LOD = 3 46 p = 0.00003，102 cM，LOD = 2.22； 0.00070；和 Chr. 13，LOD = 2.50；p = 0.00035) 第一个暗示性关联来自样本的子集，即具有 AN 限制性亚型的个体。其他结果是通过将两个协变量（饮食失调清单 2 中的瘦身动力和耶鲁-布朗强迫量表的总分）纳入基于协变量的连锁分析而获得的。基于这些非常有希望的连锁发现，我们相信可以通过扩大试点样本来绘制与 AN 相关的基因。因此，需要支持多中心努力收集 400 对受影响的 AN 亲属。在五年内，11 个合作小组（10 个临床小组，1 个分析小组）将从 400 个多重 AN 家族收集诊断和其他表型数据以及血液样本。匹兹堡大学就是这些研究小组之一。每个组织都作为一组合作 RO 提交几乎相同的申请。将使用所有新家族在整个基因组中以 H 10 cM 间隔对微卫星进行基因分型。将使用诊断和表型数据进行连锁分析，以确认试点研究中的暗示性连锁并确定新的感兴趣的基因组区域。诊断和遗传数据以及淋巴母细胞系（源自血液样本）将成为通过 NIMH 遗传学计划进行 AN 遗传研究的国家档案资源的一部分。