Copy number variations in 6q14.1 and 5q13.2 are associated with alcohol dependence.
Copy number variations in 6q14.1 and 5q13.2 are associated with alcohol dependence.
复制标题
DOI：
10.1111/j.1530-0277.2012.01758.x
复制
发表时间：
2012-09
期刊：
影响因子：
--
通讯作者：
COGEND Collaborators, GENEVA
中科院分区：
文献类型：
--
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
过度饮酒是可预防死亡的第三大原因，与酒精依赖（一种遗传表型）高度相关。已经发现了许多酒精依赖的遗传因素，但许多仍然未知。为了寻找更多的遗传因素，我们在成瘾研究：遗传学与环境（SAGE）中研究了DSM-IV酒精依赖与所有常见拷贝数变异（CNV）之间的关联。SAGE的所有参与者都接受了酒精中毒遗传学半结构化评估（SSAGA）的采访，作为三项贡献研究的一部分。在Illumina Human 1 M阵列上对2，610个非西班牙裔欧洲裔美国人样本进行基因分型。我们通过CNVpartition、PennCNV和QuantiSNP进行CNV调用，并且仅检查由所有三种软件程序鉴定的CNV。与CNV（作为缺失/重复）以及与CNV区域中的探针进行关联。在实验室中使用定量聚合酶链反应（qPCR）来验证CNV。6q14.1（P= 1.04 × 10−6）和5q13.2（P= 3.37 × 10−4）的CNVs在调整多项测试后与酒精依赖显著相关。在染色体5q13.2上，存在先前与各种神经系统疾病相关的多个候选基因。染色体6q14.1上的区域是一个基因沙漠，与智力迟钝和语言迟缓有关。通过qPCR验证了5q13.2中的CNV，而仅验证了6q14.1上的CNV组分。因此，6q14.1上的CNV应谨慎看待。这是第一项显示DSM-IV酒精依赖和CNVs之间相关性的研究。先前与神经系统疾病相关的区域中的CNV可能与酒精依赖相关。
Excessive alcohol use is the third leading cause of preventable death and is highly correlated with alcohol dependence, a heritable phenotype. Many genetic factors for alcohol dependence have been found, but many remain unknown. In search of additional genetic factors, we examined the association between DSM-IV alcohol dependence and all common copy number variations (CNV) with good reliability in the Study of Addiction: Genetics and Environment (SAGE). All participants in SAGE were interviewed using the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA), as a part of three contributing studies. 2,610 non-Hispanic European American samples were genotyped on the Illumina Human 1M array. We performed CNV calling by CNVpartition, PennCNV and QuantiSNP and only CNVs identified by all three software programs were examined. Association was conducted with the CNV (as a deletion/duplication) as well as with probes in the CNV region. Quantitative polymerase chain reaction (qPCR) was used to validate the CNVs in the laboratory. CNVs in 6q14.1 (P= 1.04 × 10−6) and 5q13.2 (P= 3.37 × 10−4) were significantly associated with alcohol dependence after adjusting multiple tests. On chromosome 5q13.2 there were multiple candidate genes previously associated with various neurological disorders. The region on chromosome 6q14.1 is a gene desert that has been associated with mental retardation, and language delay. The CNV in 5q13.2 was validated whereas only a component of the CNV on 6q14.1 was validated by qPCR. Thus, the CNV on 6q14.1 should be viewed with caution. This is the first study to show an association between DSM-IV alcohol dependence and CNVs. CNVs in regions previously associated with neurological disorders may be associated with alcohol dependence.
登录
查看更多内容
DOI：
10.1097/nen.0b013e31821cbd8b
发表时间：
2011-06-01
影响因子：
3.2
作者：
Dachs, Elisabet;Hereu, Marta;Esquerda, Josep E.
通讯作者：
Esquerda, Josep E.
影响因子：
30.8
作者：
Perry, George H.;Dominy, Nathaniel J.;Stone, Anne C.
通讯作者：
Stone, Anne C.
DOI：
10.1002/ajmg.b.30498
发表时间：
2007-04-05
影响因子：
2.8
作者：
Lachman, Herbert M.;Pedrosa, Erika;Stopkova, Pavla
通讯作者：
Stopkova, Pavla
DOI：
10.1111/j.1530-0277.2010.01156.x
发表时间：
2010-05
期刊：
Alcoholism, clinical and experimental research
影响因子：
--
作者：
Edenberg HJ;Koller DL;Xuei X;Wetherill L;McClintick JN;Almasy L;Bierut LJ;Bucholz KK;Goate A;Aliev F;Dick D;Hesselbrock V;Hinrichs A;Kramer J;Kuperman S;Nurnberger JI Jr;Rice JP;Schuckit MA;Taylor R;Todd Webb B;Tischfield JA;Porjesz B;Foroud T
通讯作者：
Foroud T
影响因子：
14.9
作者：
Diskin SJ;Li M;Hou C;Yang S;Glessner J;Hakonarson H;Bucan M;Maris JM;Wang K
通讯作者：
Wang K