Significant linkage on chromosome 10p in families with bulimia nervosa
Significant linkage on chromosome 10p in families with bulimia nervosa
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DOI：
10.1086/345801
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发表时间：
2003-01-01
影响因子：
9.8
通讯作者：
Kaye, WH
中科院分区：
文献类型：
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作者：
Bulik, CM;Devlin, B;Kaye, WH
神经性贪食症（BN）是强烈的家族性，和添加剂的遗传效应似乎大大有助于观察到的家族性。反过来，BN的行为成分，如自我诱发的呕吐，是可靠的测量和遗传的。为了确定基因组区域的窝藏遗传变异赋予BN的易感性，我们进行了连锁分析的多重家庭与饮食失调，确定通过先证者与BN。308个家庭的整个样本的连锁分析产生了一个双峰，最高的非参数多点最大LOD得分（MLS），2.92，在染色体10。鉴于自我诱发呕吐的高遗传性及其可测量的可靠性，我们在一个子集（n = 133）的家庭中进行了连锁分析，其中至少有两个受影响的亲属报告了包括自我诱发呕吐的症状模式。观察到的最高MLS（3.39）在10号染色体上，在标记D10 S1430和D10 S1423之间。这些结果提供了染色体10 p上存在BN易感性位点的证据。使用模拟，我们证明了这两个分数，2.92和3.39，满足广泛接受的全基因组意义的标准。14 q上的另一个区域符合全基因组暗示连锁的标准，在距p-ter 62厘摩处的MLSs为1.97（全样本）和1.75（子集）。
Bulimia nervosa (BN) is strongly familial, and additive genetic effects appear to contribute substantially to the observed familiality. In turn, behavioral components of BN, such as self-induced vomiting, are reliably measured and heritable. To identify regions of the genome harboring genetic variants conferring susceptibility to BN, we conducted a linkage analysis of multiplex families with eating disorders that were identified through a proband with BN. Linkage analysis of the entire sample of 308 families yielded a double peak, with the highest nonparametric multipoint maximum LOD score (MLS), of 2.92, on chromosome 10. Given the high heritability of self-induced vomiting and the reliability with which it can be measured, we performed linkage analysis in a subset (n = 133) of families in which at least two affected relatives reported a symptom pattern that included self-induced vomiting. The highest MLS (3.39) observed was on chromosome 10, between markers D10S1430 and D10S1423. These results provide evidence of the presence of a susceptibility locus for BN on chromosome 10p. Using simulations, we demonstrate that both of these scores, 2.92 and 3.39, meet the widely accepted criterion for genomewide significance. Another region on 14q meets the criterion for genomewide suggestive linkage, with MLSs of 1.97 (full sample) and 1.75 (subset) at 62 centimorgans from p-ter.