Genome-wide association study of alcohol dependence implicates a region on chromosome 11.
Genome-wide association study of alcohol dependence implicates a region on chromosome 11.
复制标题
DOI：
10.1111/j.1530-0277.2010.01156.x
复制
发表时间：
2010-05
期刊：
影响因子：
--
通讯作者：
Foroud T
中科院分区：
文献类型：
--
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
酒精依赖是一种复杂的疾病，尽管连锁和候选基因研究已经确定了几个与酒精中毒风险相关的基因，但这些基因只能解释部分风险。我们进行了全基因组关联研究（GWAS）的病例对照样本从家庭的合作研究酒精中毒的遗传学。所有病例均符合美国精神病学协会诊断和统计手册第四版（DSM-IV）酒精依赖的诊断标准;对照组均饮酒，但不依赖酒精或非法药物。为了优先考虑最强的候选人，我们对酒精依赖家庭样本中前199个SNP中的大多数进行了基因分型（p ≤ 2.1 × 10−4），并进行了基于谱系的关联分析。我们还研究了携带最高SNPs的基因是否在人脑中表达或在淋巴母细胞中乙醇存在下差异表达。虽然没有一个SNP符合全基因组的显著性标准，但有几个SNP簇提供了相互支持。结合病例对照研究、家族随访和基因表达的证据，为11号染色体上的一组基因（SLC 22 A18、PHLDA 2、NAP 1 L4、SNORA 54、汽车和OSBPL 5）与酒精依赖的关联提供了最有力的支持。在早期的GWAS研究中被提名为候选者的几个SNP在我们的研究中重复，包括CPE，DNASE 2B，SLC 10A 2，ARL 6 IP 5，ID 4，GATA 4，SYN 1和ADCY 3。我们已经确定了几个有希望的协会，值得进一步研究的独立样本。
Alcohol dependence is a complex disease, and although linkage and candidate gene studies have identified several genes associated with the risk for alcoholism, these explain only a portion of the risk. We carried out a genome-wide association study (GWAS) on a case-control sample drawn from the families in the Collaborative Study on the Genetics of Alcoholism. The cases all met diagnostic criteria for alcohol dependence according to the Diagnostic and Statistical Manual of the American Psychiatric Association Fourth Edition (DSM-IV); controls all consumed alcohol but were not dependent on alcohol or illicit drugs. To prioritize among the strongest candidates, we genotyped most of the top 199 SNPs (p ≤ 2.1 × 10−4) in a sample of alcohol dependent families and performed pedigree-based association analysis. We also examined whether the genes harboring the top SNPs were expressed in human brain or were differentially expressed in the presence of ethanol in lymphoblastoid cells. Although no single SNP met genome-wide criteria for significance, there were several clusters of SNPs that provided mutual support. Combining evidence from the case-control study, the followup in families, and gene expression provided strongest support for the association of a cluster of genes on chromosome 11 (SLC22A18, PHLDA2, NAP1L4, SNORA54, CARS, and OSBPL5) with alcohol dependence. Several SNPs nominated as candidates in earlier GWAS studies replicated in ours, including CPE, DNASE2B, SLC10A2,ARL6IP5, ID4, GATA4, SYNE1 and ADCY3. We have identified several promising associations that warrant further examination in independent samples.
登录
查看更多内容
DOI：
10.1038/npp.2008.171
发表时间：
2009-04
期刊：
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
影响因子：
--
作者：
通讯作者：
--
影响因子：
6
作者：
Dick, Danielle M.;Agrawal, Arpana;Bierut, Laura J.
通讯作者：
Bierut, Laura J.
影响因子：
9.8
作者：
Edenberg, HJ;Dick, DM;Begleiter, H
通讯作者：
Begleiter, H
影响因子：
9.8
作者：
Abecasis, GR;Cardon, LR;Cookson, WOC
通讯作者：
Cookson, WOC
影响因子：
3.5
作者：
Edenberg HJ;Wang J;Tian H;Pochareddy S;Xuei X;Wetherill L;Goate A;Hinrichs T;Kuperman S;Nurnberger JI Jr;Schuckit M;Tischfield JA;Foroud T
通讯作者：
Foroud T