ASTN1 and alcohol dependence: family-based association analysis in multiplex alcohol dependence families.
ASTN1 and alcohol dependence: family-based association analysis in multiplex alcohol dependence families.
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DOI：
10.1002/ajmg.b.32048
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发表时间：
2012-06
影响因子：
2.8
通讯作者：
Stiffler, Scott
中科院分区：
文献类型：
--
作者：
Hill, Shirley Y.;Weeks, Daniel E.;Jones, Bobby L.;Zezza, Nicholas;Stiffler, Scott
酒精依赖（AD）在多重家庭中的一项全基因组连锁研究发现，1号染色体上靠近微卫星标记D1S196和D1S2878的区域存在连锁结果。ASTN 1基因位于该区域，该基因先前被报道与药物滥用、双相情感障碍和精神分裂症有关。使用由330个具有表型数据和DNA的个体组成的相同家族数据，使用HapMap CEU群体，使用次要等位基因频率（MAF）≥ 0.15和成对连锁不平衡（LD）r2 <0.8的SNP对以D1S196为中心的26 cM区域进行更精细的作图。在ASTN 1基因内的4个SNP（rs465066、rs228008、rs6668092和rs172917）中观察到显著的FBAT P值，最显著的是内含子8内的rs228008，P值为0.001。使用MQLS，它允许包括所有家庭，我们发现这些SNPs中的三个具有MQLS P值<0.003。此外，两个额外的相邻SNP（rs10798496和rs6667588）分别在P = 0.002和0.03处显示出显著性。使用FBAT的基于单倍型的测试功能对包括rs228008、rs6668092和rs172917的区块进行单倍型分析。该分析发现，一种阻断剂（GCG）过度传播，另一种阻断剂（ATA）向受影响后代传播不足。连锁分析确定了一个与关联结果一致的区域。基于家系的关联分析显示ASTN 1基因与酒精依赖显著相关。ASTN 1基因对AD风险的潜在重要性可能与其在胶质细胞引导的神经元迁移中的作用有关。
A previous genome-wide linkage study of alcohol dependence (AD) in multiplex families found a suggestive linkage result for a region on Chromosome 1 near microsatellite markers D1S196 and D1S2878. The ASTN1 gene is in this region, a gene previously reported to be associated with substance abuse, bipolar disorder and schizophrenia. Using the same family data consisting of 330 individuals with phenotypic data and DNA, finer mapping of a 26 cM region centered on D1S196 was undertaken using SNPs with minor allele frequency (MAF) ≥ 0.15 and pair-wise linkage disequilibrium (LD) of r2 <0.8 using the HapMap CEU population. Significant FBAT P-values for SNPs within the ASTN1 gene were observed for four SNPs (rs465066, rs228008, rs6668092, and rs172917), the most significant, rs228008, within intron 8 had a P-value of 0.001. Using MQLS, which allows for inclusion of all families, we find three of these SNPs with MQLS P-values <0.003. In addition, two additional neighboring SNPs (rs10798496 and rs6667588) showed significance at P = 0.002 and 0.03, respectively. Haplotype analysis was performed using the haplotype-based test function of FBAT for a block that included rs228008, rs6668092, and rs172917. This analysis found one block (GCG) over-transmitted and another (ATA) under-transmitted to affected offspring. Linkage analysis identified a region consistent with the association results. Family-based association analysis shows the ASTN1 gene significantly associated with alcohol dependence. The potential importance of the ASTN1 gene for AD risk may be related its role in glial-guided neuronal migration.
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影响因子：
10.6
作者：
Hill, Shirley Y.;Wang, Shuhui;Kostelnik, Bryan;Carter, Howard;Holmes, Brian;McDermott, Michael;Zezza, Nicholas;Stiffier, Scott;Keshavan, Matcheri S.
通讯作者：
Keshavan, Matcheri S.
影响因子：
9.8
作者：
Edenberg, HJ;Dick, DM;Begleiter, H
通讯作者：
Begleiter, H
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
影响因子：
56.9
作者：
Gabriel, SB;Schaffner, SF;Altshuler, D
通讯作者：
Altshuler, D
影响因子：
--
作者：
FEIGHNER, JP;WOODRUFF, RA;GUZE, SB
通讯作者：
GUZE, SB