Frequency of rare allelic variation in candidate genes among individuals with low and high urinary calcium excretion.
Frequency of rare allelic variation in candidate genes among individuals with low and high urinary calcium excretion.
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DOI：
10.1371/journal.pone.0071885
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Curhan GC
中科院分区：
文献类型：
--
作者：
Toka HR;Genovese G;Mount DB;Pollak MR;Curhan GC
我们的研究调查了罕见的等位基因变异与24小时尿钙排泄极端的相关性，因为尿钙排泄较高是钙基肾结石形成的主要危险因素。我们从护士健康研究I和II以及卫生专业人员随访研究中对40个可能与个体尿钙排泄相关的候选基因进行了重新测序。根据可获得的24小时尿液采集数据和尿钙排泄水平(低与高)，总共选择了960名参与者。我们利用了DNA样本池、基于液滴的靶基因浓缩、多路复用和高通量测序。大约%的样本(n = 615)同时显示了成功的靶浓缩和测序数据，>；20倍深度覆盖。共鉴定出259个新的等位基因变异。没有发现罕见的基因变异(等位基因频率和2%)在低尿钙组和高尿钙组中频率增加；大多数这些变异只在单个个体中观察到。对等位基因频率为≥2%的变异的未校正分析表明，Claudin14SNP rs113831133与低尿钙排泄量相关(6/520vs29/710单倍型，P值 = 0.003)。我们的数据，加上之前的人类和动物研究，表明Claudin14可能在尿钙排泄中发挥作用。为了证实我们对rs113831133的发现，有必要在更大的样本集中进行遗传验证研究。在测试的一组候选基因中，罕见的等位基因变异似乎对个体之间的尿钙排泄差异没有显著影响。
Our study investigated the association of rare allelic variants with extremes of 24-hour urinary calcium excretion because higher urinary calcium excretion is a dominant risk factor for calcium-based kidney stone formation. We resequenced 40 candidate genes potentially related to urinary calcium excretion in individuals from the Nurses' Health Studies I & II and the Health Professionals Follow-up Study. A total of 960 participants were selected based on availability of 24-hour urine collection data and level of urinary calcium excretion (low vs. high). We utilized DNA sample pooling, droplet-based target gene enrichment, multiplexing, and high-throughput sequencing. Approximately 64% of samples (n = 615) showed both successful target enrichment and sequencing data with >20-fold deep coverage. A total of 259 novel allelic variants were identified. None of the rare gene variants (allele frequencies <2%) were found with increased frequency in the low vs. high urinary calcium groups; most of these variants were only observed in single individuals. Unadjusted analysis of variants with allele frequencies ≥2% suggested an association of the Claudin14 SNP rs113831133 with lower urinary calcium excretion (6/520 versus 29/710 haplotypes, P value = 0.003). Our data, together with previous human and animal studies, suggest a possible role for Claudin14 in urinary calcium excretion. Genetic validation studies in larger sample sets will be necessary to confirm our findings for rs113831133. In the tested set of candidate genes, rare allelic variants do not appear to contribute significantly to differences in urinary calcium excretion between individuals.
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影响因子：
3.5
作者：
Fahmi, Saleemah;Yang, Chendong;Cohen, Jonathan C.
通讯作者：
Cohen, Jonathan C.
影响因子：
158.5
作者：
CURHAN, GC;WILLETT, WC;STAMPFER, MJ
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STAMPFER, MJ
使用下一代 DNA 测序数据进行变异发现和基因分型的框架。
影响因子：
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作者：
通讯作者：
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影响因子：
15.9
作者：
Dawson, Paul A.;Russell, Christopher S.;Markovich, Daniel
通讯作者：
Markovich, Daniel
影响因子：
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作者：
Heneghan, John F.;Akhavein, Arash;Alper, Seth L.
通讯作者：
Alper, Seth L.