How many cases of disease in a pedigree imply familial disease?
How many cases of disease in a pedigree imply familial disease?
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DOI：
10.1111/ahg.12222
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发表时间：
2018-03
影响因子：
1.9
通讯作者：
Walsh JP
中科院分区：
文献类型：
--
作者：
Dudbridge F;Brown SJ;Ward L;Wilson SG;Walsh JP
对大量个体进行全外显子组和越来越多的全基因组测序的能力，导致人们更加努力地识别影响常见和罕见疾病风险的罕见遗传变异。在这样的应用中，重要的是鉴定分离感兴趣的罕见变体的家族。对于罕见疾病或常见疾病的罕见家族形式，多个受影响成员的家系显然存在风险变异。然而，对于更常见的疾病，可能不清楚一个有几个受影响成员的家庭是否分离了家族性疾病，是多个散发病例的结果，还是家族性病例和表型的混合物。我们提供了计算的概率，一个家庭是窝藏家族性疾病，一般而言，承认目前的测序研究选择家庭的工作准则。使用我们自己的甲状腺癌研究和已发表的结直肠癌研究所激发的例子，我们表明，对于常见疾病，有两个受影响的一级亲属的家庭只有中等的概率分离家族性疾病，但对于有三个或更多受影响亲属的家庭，这种概率更高，因此这些家庭应该优先进行测序研究。
The ability to perform whole‐exome and, increasingly, whole‐genome sequencing on large numbers of individuals has led to increased efforts to identify rare genetic variants that affect the risk of both common and rare diseases. In such applications, it is important to identify families that are segregating the rare variants of interest. For rare diseases or rare familial forms of common diseases, pedigrees with multiple affected members are clearly harbouring risk variants. For more common diseases, however, it may be unclear whether a family with a few affected members is segregating a familial disease, is the result of multiple sporadic cases, or is a mixture of familial cases and phenocopies. We provide calculations for the probability that a family is harbouring familial disease, presented in general terms that admit working guidelines for selecting families for current sequencing studies. Using examples motivated by our own studies of thyroid cancer and published studies of colorectal cancer, we show that for common diseases, families with exactly two affected first‐degree relatives have only a moderate probability of segregating familial disease, but this probability is higher for families with three or more affected relatives, and those families should therefore be prioritised in sequencing studies.
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影响因子：
4.5
作者：
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通讯作者：
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通讯作者：
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通讯作者：
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作者：
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通讯作者：
Ghobrial, Irene M.