Genome-wide association discoveries of alcohol dependence.
Genome-wide association discoveries of alcohol dependence.
复制标题
DOI：
10.1111/j.1521-0391.2014.12147.x
复制
发表时间：
2014-11
期刊：
影响因子：
--
通讯作者：
Luo X
中科院分区：
文献类型：
--
作者：
Zuo L;Lu L;Tan Y;Pan X;Cai Y;Wang X;Hong J;Zhong C;Wang F;Zhang XY;Vanderlinden LA;Tabakoff B;Luo X
报告全基因组范围内显著和/或可复制的酒精依赖风险变异，并探讨其潜在的生物学功能。我们在PubMed中搜索了所有酒精依赖的全基因组关联研究（GWAS）。我们提取了以下三种类型的结果：单个样本、组合样本或荟萃分析中的全基因组显著关联（p<5×10−8）;单个样本中排名最高的关联（p<10−5），在其他样本中名义上是可复制的（p<0.05）;以及至少三个独立的GWAS样本中名义上是可复制的关联（p<0.05）。对这些结果进行了荟萃分析。分析了人类中的cis-eQTL、大鼠和小鼠脑中的RNA表达以及所有这些风险变体的生物信息学特性。在至少一个样本中，位于ADH簇内的变异在全基因组水平上与酒精依赖显著相关（p<5×10−8）。与ADH簇的一些关联在六个独立的GWAS样本中是可复制的。在荟萃分析或合并样本中，位于SERINC 2、KIAA 0040、MREG-PECR或PKNOX 2内或附近的变异体在全基因组水平上与酒精依赖显著相关（p<5×10−8），并且这些关联在至少一个样本中是可复制的。在一些样本中，与NRD 1、GPD 1 L-CMTM 8或MAP 3 K9-PCNX内的变异的关联是暗示性的（5×10−8<p<10−5），并且在其他样本中名义上是可复制的。与HTR 7和OPA 3变异的关联在至少三个独立的GWAS样本中名义上是可复制的（10−5<p<0.05）。ADH簇中的一些危险变异体，SERINC 2、KIAA 0040、NRD 1和HTR 7具有潜在的生物学功能。最强大的风险位点是ADH集群。SERINC 2、KIAA 0040、NRD 1和HTR 7也可能在酒精依赖中起重要作用。根据功能分析，PKNOX 2、MREG、PECR、GPD 1 L、CMTM 8、MAP 3 K9、PCNX和OPA 3在酒精依赖风险中的作用可能较小。这一结论将有助于GWAS后酒精依赖的后续研究。
To report the genome-wide significant and/or replicable risk variants for alcohol dependence and explore their potential biological functions. We searched in PubMed for all genome-wide association studies (GWASs) of alcohol dependence. The following three types of the results were extracted: genome-wide significant associations in an individual sample, the combined samples, or the meta-analysis (p<5×10−8); top-ranked associations in an individual sample (p<10−5) that were nominally replicated in other samples (p<0.05); and nominally replicable associations across at least three independent GWAS samples (p<0.05). These results were meta-analyzed. cis-eQTLs in human, RNA expression in rat and mouse brain and bioinformatics properties of all of these risk variants were analyzed. The variants located within ADH cluster were significantly associated with alcohol dependence at genome-wide level (p<5×10−8) in at least one sample. Some associations with the ADH cluster were replicable across six independent GWAS samples. The variants located within or near SERINC2, KIAA0040, MREG-PECR or PKNOX2 were significantly associated with alcohol dependence at genome-wide level (p<5×10−8) in meta-analysis or combined samples, and these associations were replicable across at least one sample. The associations with the variants within NRD1, GPD1L-CMTM8 or MAP3K9-PCNX were suggestive (5×10−8<p<10−5) in some samples, and nominally replicable in other samples. The associations with the variants at HTR7 and OPA3 were nominally replicable across at least three independent GWAS samples (10−5<p<0.05). Some risk variants at the ADH cluster, SERINC2, KIAA0040, NRD1 and HTR7 had potential biological functions. The most robust risk locus was the ADH cluster. SERINC2, KIAA0040, NRD1 and HTR7 were also likely to play important roles in alcohol dependence. PKNOX2, MREG, PECR, GPD1L, CMTM8, MAP3K9, PCNX and OPA3 might play less important roles in risk for alcohol dependence based on the function analysis. This conclusion will significantly contribute to the post-GWAS follow-up studies on alcohol dependence.
登录
查看更多内容
DOI：
10.1002/ajmg.b.32048
发表时间：
2012-06
影响因子：
2.8
作者：
Hill, Shirley Y.;Weeks, Daniel E.;Jones, Bobby L.;Zezza, Nicholas;Stiffler, Scott
通讯作者：
Stiffler, Scott
剪接的组织特异性遗传控制：对复杂性状的研究的影响。
影响因子：
9.8
作者：
Heinzen EL;Ge D;Cronin KD;Maia JM;Shianna KV;Gabriel WN;Welsh-Bohmer KA;Hulette CM;Denny TN;Goldstein DB
通讯作者：
Goldstein DB
DOI：
10.1002/ajmg.b.30902
发表时间：
2009-09-05
影响因子：
2.8
作者：
Gratacos, Monica;Costas, Javier;Carracedo, Angel
通讯作者：
Carracedo, Angel
DOI：
10.1111/j.1530-0277.2010.01173.x
发表时间：
2010-06
期刊：
Alcoholism, clinical and experimental research
影响因子：
--
作者：
Chen AC;Manz N;Tang Y;Rangaswamy M;Almasy L;Kuperman S;Nurnberger J Jr;O'Connor SJ;Edenberg HJ;Schuckit MA;Tischfield J;Foroud T;Bierut LJ;Rohrbaugh J;Rice JP;Goate A;Hesselbrock V;Porjesz B
通讯作者：
Porjesz B
酒精依赖性与ADH基因簇中的变体之间的全基因组显着关联。
影响因子：
3.4
作者：
Frank J;Cichon S;Treutlein J;Ridinger M;Mattheisen M;Hoffmann P;Herms S;Wodarz N;Soyka M;Zill P;Maier W;Mössner R;Gaebel W;Dahmen N;Scherbaum N;Schmäl C;Steffens M;Lucae S;Ising M;Müller-Myhsok B;Nöthen MM;Mann K;Kiefer F;Rietschel M
通讯作者：
Rietschel M