Genetics of Anorexia Nervosa

描述（由申请人提供）：神经性厌食症（AN）是一种慢性且经常致命的疾病，影响0.3%的女性。目前还没有fda批准的治疗方法，死亡率为每十年5%。除了环境影响外，家庭和双胞胎研究也证明了AN的遗传性。由于这种毁灭性疾病的病因尚不清楚，我们进行了一项初步研究，以检查其遗传基础。在一个私人基金会的支持下，我们的多中心合作已经从北美和欧洲的7个地点收集了196种多路AN。在有限的样本中，这项初步研究从全基因组扫描中得出了四个具有启发性的联系，其中一个非常接近全基因组意义（染色体1在70厘米处，p - 0.0001；染色体1在202厘米处，LOD = 3 46）。P = 0.00003；Chr. 2在102 cM处，LOD = 2.22, p = 0.00070；在102 cM处ch13。Lod = 2.50；p = 0.00035)第一个暗示性联系来自样本的一个子集，即具有AN限制性亚型的个体。其他结果是通过结合两个协变量，即饮食失调量表-2中的减肥动力和耶鲁-布朗强迫症量表的总分，进行基于协变量的关联分析而获得的。基于这些非常有希望的联系发现，我们相信可以通过增加试点样本来绘制AN潜在责任的基因。因此，要求支持多中心努力收集400对受影响的AN相关对。在5年的时间里，11个合作小组（10个临床小组，1个分析小组）将收集400多种AN的诊断和其他表型数据以及血液样本。匹兹堡大学是这些研究小组之一。作为一组协作的r01，每个r01都提交了几乎相同的应用程序。微卫星将使用所有新家族在基因组中每隔10厘米进行基因分型。将使用诊断和表型数据进行连锁分析，以确认初步研究的暗示联系，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（来自血液样本）将通过NIMH遗传学倡议成为AN遗传研究的国家档案资源的一部分。

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 R01s. 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.