A meta-analysis of two genome-wide association studies to identify novel loci for maximum number of alcoholic drinks.
A meta-analysis of two genome-wide association studies to identify novel loci for maximum number of alcoholic drinks.
复制标题
对两项全基因组关联研究的荟萃分析，以鉴定最大含酒精饮料的新基因座。
DOI：
10.1007/s00439-013-1318-z
复制
发表时间：
2013-10
期刊：
影响因子：
5.3
通讯作者：
Goate, Alison
中科院分区：
文献类型：
--
作者：
Kapoor, Manav;Wang, Jen-Chyong;Wetherill, Leah;Le, Nhung;Bertelsen, Sarah;Hinrichs, Anthony L.;Budde, John;Agrawal, Arpana;Bucholz, Kathleen;Dick, Danielle;Harari, Oscar;Hesselbrock, Victor;Kramer, John;Nurnberger, John I., Jr.;Rice, John;Saccone, Nancy;Schuckit, Marc;Tischfield, Jay;Porjesz, Bernice;Edenberg, Howard J.;Bierut, Laura;Foroud, Tatiana;Goate, Alison
24 小时内饮酒的最大数量 (maxdrinks) 是一种可遗传的 (> 50%) 特征，与过度饮酒和随后的酒精依赖 (AD) 的脆弱性密切相关。一些全基因组关联研究（GWAS）研究了酒精依赖，但很少有人关注过度饮酒。我们使用 maxdrinks 作为过度饮酒表型进行了两次 GWAS：其中一个是从酒精中毒遗传学合作研究 (COGA) 中选出的 118 个大家庭 (N=2322)，另一个是来自成瘾研究：基因与环境 (SAGE) 的病例对照样本 (N=2593)。 COGA 家族中最强的关联是通过位于染色体 13q31.1 基因间区域的 rs9523562 (p = 2.1×10−6) 检测到的； SAGE 数据集中最强的关联是与 rs67666182 (p = 7.1×10−7)，位于 8 号染色体上的基因间区域。我们还对这两个 GWAS 进行了荟萃分析，并证明了两个数据集中 LMO1 (p = 7.2×10−7) 和 PLCL1 基因 (p = 4.1×10−6) 与 maxdrinks 增加的关联证据。 AUTS2 的变异以及 INADL、C15orf32 和 HIP1 的变异与 GWAS 研究荟萃分析中的饮酒量相关，以及酒精消费因子评分的 GWAS 在当前的荟萃分析中也显示出名义关联。本研究已确定了几个需要在独立样本中进行进一步检查的位点。每个数据集中的顶级 SNP (p≤10−4) 在其他数据集中表现出的效应方向与偶然预期的相同 (p = 2×10−3, 3×10−6) 远多于预期 (p = 2×10−3, 3×10−6)，这表明这些顶级 SNP 中存在真实信号，即使没有 SNP 达到全基因组的显着性水平。
Maximum number of alcoholic drinks consumed in a 24-h period (maxdrinks) is a heritable (> 50%) trait and is strongly correlated with vulnerability to excessive alcohol consumption and subsequent alcohol dependence (AD). Several genome-wide association studies (GWAS) have studied alcohol dependence, but few have concentrated on excessive alcohol consumption. We performed two GWAS using maxdrinks as an excessive alcohol consumption phenotype: one in 118 extended families (N=2322) selected from the Collaborative Study on the Genetics of Alcoholism (COGA), and the other in a case-control sample (N=2593) derived from the Study of Addiction: Genes and Environment (SAGE). The strongest association in the COGA families was detected with rs9523562 (p = 2.1×10−6) located in an intergenic region on chromosome 13q31.1; the strongest association in the SAGE dataset was with rs67666182 (p = 7.1×10−7), located in an intergenic region on chromosome 8. We also performed a meta-analysis with these two GWAS and demonstrated evidence of association in both datasets for the LMO1 (p = 7.2×10−7) and PLCL1 genes (p = 4.1×10−6) with increased maxdrinks. A variant in AUTS2 and variants in INADL, C15orf32 and HIP1 that were associated with measures of alcohol consumption in a meta-analysis of GWAS studies and a GWAS of alcohol consumption factor score also showed nominal association in the current meta-analysis. The present study has identified several loci that warrant further examination in independent samples. Among the top SNPs in each of the dataset (p≤10−4) far more showed the same direction of effect in the other dataset than would be expected by chance (p = 2×10−3, 3×10−6), suggesting that there are true signals among these top SNPs, even though no SNP reached genome-wide levels of significance.
登录
查看更多内容
影响因子：
9.8
作者：
Liu, Jimmy Z.;Mcrae, Allan F.;Macgregor, Stuart
通讯作者：
Macgregor, Stuart
影响因子：
10.6
作者：
Grant, Julia D.;Agrawal, Arpana;Bucholz, Kathleen K.;Madden, Pamela A. F.;Pergadia, Michele L.;Nelson, Elliot C.;Lynskey, Michael T.;Todd, Richard D.;Todorov, Alexandre A.;Hansell, Narelle K.;Whitfield, John B.;Martin, Nicholas G.;Heath, Andrew C.
通讯作者：
Heath, Andrew C.
影响因子：
7.1
作者：
Agrawal, Arpana;Freedman, Neal D.;Bierut, Laura J.
通讯作者：
Bierut, Laura J.
影响因子：
7.1
作者：
Baik, Inkyung;Cho, Nam H.;Shin, Chol
通讯作者：
Shin, Chol
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