Association between copy number variation losses and alcohol dependence across African American and European American ethnic groups.
Association between copy number variation losses and alcohol dependence across African American and European American ethnic groups.
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DOI：
10.1111/acer.12364
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发表时间：
2014-05
期刊：
影响因子：
--
通讯作者：
Liu J
中科院分区：
文献类型：
--
作者：
Ulloa AE;Chen J;Vergara VM;Calhoun V;Liu J
拷贝数变异（CNVs）是由DNA序列中的片段增加或丢失组成的结构性遗传突变。虽然CNVs对基因组变异有很大贡献，但很少有遗传学和影像学研究报告CNVs与酒精依赖（AD）相关。我们的目的是找到这种关联在不同种族和性别之间的证据。这项工作是第一个跨种族的AD-CNV研究，也是第一个包括非洲裔美国人的研究。这项研究考虑了两个CNV数据集，一个用于发现（2，345个样本），另一个用于验证（239个样本），两者都包括AD受试者和欧洲和非洲血统的健康对照。我们的分析通过检查整个基因组的整体损失，单个细胞遗传学条带内的集体损失和CNV区域的特定损失的影响，评估了AD和CNV损失之间的关联。来自发现数据集的结果显示16q12.2内的CNV丢失与AD诊断之间存在关联（p = 4.53x10−3）。来自验证数据集的重叠CNV区域表现出与AD相同的作用方向（p = 0.051）。该CNV区域影响羧酸酯酶（CES）家族的成员基因CES 1 p1和CES 1。由CES 1编码的酶是一种主要的肝酶，其通常催化酯分解为醇和羧酸，并且参与药物或外源性物质、脂肪酸和胆固醇代谢。此外，在我们的发现数据集中，最显著相关的CNV区域位于9p21.2（p = 1.9×10−3）。尽管在验证数据集中未观察到，可能是由于样本量小，但鉴于其与神经元死亡的关系，该结果可能与AD存在潜在联系。相比之下，我们没有发现AD与总体总损失或个体细胞遗传学条带内的集体损失之间的任何关联。总的来说，我们的研究提供了证据表明，在16q12.2的特定CNV有助于非洲裔美国人和欧洲裔美国人人群的酒精中毒的发展。
Copy number variations (CNVs) are structural genetic mutations consisting of segmental gains or losses in DNA sequence. Although CNVs contribute substantially to genomic variation, few genetic and imaging studies report association of CNVs with alcohol dependence (AD). Our purpose is to find evidence of this association across ethnic populations and genders. This work is the first AD-CNV study across ethnic groups and the first to include the African American population. This study considers two CNV datasets, one for discovery (2,345 samples) and the other for validation (239 samples), both including subjects with AD and healthy controls of European and African ancestry. Our analysis assesses the association between AD and CNV losses across ethnic groups and gender by examining the effect of overall losses across the whole genome, collective losses within individual cytogenetic bands and specific losses in CNV regions. Results from the discovery dataset showed an association between CNV losses within 16q12.2 and AD diagnosis (p = 4.53x10−3). An overlapping CNV region from the validation dataset exhibited the same direction of effect with respect to AD (p = 0.051). This CNV region affects the genes CES1p1 and CES1, which are members of the carboxylesterase (CES) family. The enzyme encoded by CES1 is a major liver enzyme that typically catalyzes the decomposition of ester into alcohol and carboxylic acid and is involved in drug or xenobiotics, fatty acid and cholesterol metabolisms. In addition, the most significantly associated CNV region was located at 9p21.2 (p = 1.9×10−3) in our discovery dataset. Although not observed in the validation dataset, probably due to small sample size, this result might hold potential connection to AD given its connection with neuronal death. In contrast, we did not find any association between AD and the overall total losses or the collective losses within individual cytogenetic bands. Overall, our study provides evidence that the specific CNVs at 16q12.2 contribute to the development of alcoholism in African American and European American populations.
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影响因子：
3.8
作者：
Boccia S;Sayed-Tabatabaei FA;Persiani R;Gianfagna F;Rausei S;Arzani D;La Greca A;D'Ugo D;La Torre G;van Duijn CM;Ricciardi G
通讯作者：
Ricciardi G
影响因子：
4.2
作者：
Bierut, Laura Jean;Strickland, Jaime R.;Cottler, Linda B.
通讯作者：
Cottler, Linda B.
影响因子：
30.8
作者：
Iafrate, AJ;Feuk, L;Lee, C
通讯作者：
Lee, C
影响因子：
56.9
作者：
Gonzalez, E;Kulkarni, H;Ahuja, SK
通讯作者：
Ahuja, SK
DOI：
10.1111/j.1530-0277.2012.01758.x
发表时间：
2012-09
期刊：
Alcoholism, clinical and experimental research
影响因子：
--
作者：
Lin P;Hartz SM;Wang JC;Agrawal A;Zhang TX;McKenna N;Bucholz K;Brooks AI;Tischfield JA;Edenberg HJ;Hesselbrock VM;Kramer JR;Kuperman S;Schuckit MA;Goate AM;Bierut LJ;Rice JP;COGA Collaborators;COGEND Collaborators, GENEVA
通讯作者：
COGEND Collaborators, GENEVA