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利用一个有严重物质和行为问题的门诊就诊青少年、对照和可获得的一级亲属样本,测试 GABRA2(SNP rs279871)与青少年品行/酒精使用障碍之间的关联。

Test of association between GABRA2 (SNP rs279871) and adolescent conduct/alcohol use disorders utilizing a sample of clinic referred youth with serious substance and conduct problems, controls and available first degree relatives.

机构信息

Division of Substance Dependence, University of Colorado Denver School of Medicine, Aurora, CO 80045, USA.

出版信息

Drug Alcohol Depend. 2010 Jan 15;106(2-3):199-203. doi: 10.1016/j.drugalcdep.2009.08.015. Epub 2009 Sep 23.

Abstract

UNLABELLED

Recent findings have linked the GABRA2 gene with antisocial personality disorder and alcohol dependence (AD) in adults and conduct disorder (CD), but not AD symptoms, in children and adolescents. We sought to replicate previous findings and test for an association between a single nucleotide polymorphism (SNP) in the GABRA2 gene (rs279871) and CD among adolescents.

METHODS

Adolescent patients (n=371), 13-18 years old, were recruited from a university substance abuse treatment program. Patient siblings (n=245), parents of patients (n=355), adolescent controls (n=185), siblings of controls (n=163) and parents of controls (n=263) were included in these analyses (total sample n=1582). Case-control (using only Caucasian and Hispanic probands) and family-based association tests were completed to test for association between rs279871 and several a priori CD and AD phenotypes.

RESULTS

For case-control association tests, rs279871 was significantly associated with CD (p=0.02) but not AD phenotypes; the result did not survive strict correction for multiple testing. All family-based association tests were non-significant (CD p=0.48; CD symptom count age corrected within sex p=0.91; AD p=0.84; alcohol use disorder p=0.52).

CONCLUSIONS

Consistent with previous findings, the results do not support the association between GABRA2 SNP rs279871 and AD in adolescents. Our results also do not support an association between rs279871 and CD; the study limitations are reviewed.

摘要

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最近的研究发现,GABRA2 基因与成人的反社会人格障碍和酒精依赖(AD)以及儿童和青少年的品行障碍(CD)有关,但与 AD 症状无关。我们试图复制以前的发现,并测试 GABRA2 基因(rs279871)中的单个核苷酸多态性(SNP)与青少年 CD 之间的关联。

方法

从一所大学的物质滥用治疗计划中招募了 371 名年龄在 13 至 18 岁的青少年患者。患者的兄弟姐妹(n=245)、患者的父母(n=355)、青少年对照组(n=185)、对照组的兄弟姐妹(n=163)和对照组的父母(n=263)都包括在这些分析中(总样本 n=1582)。完成了病例对照(仅使用白人和西班牙裔先证者)和基于家庭的关联测试,以测试 rs279871 与几个先验 CD 和 AD 表型之间的关联。

结果

对于病例对照关联测试,rs279871 与 CD 显著相关(p=0.02),但与 AD 表型无关;该结果在严格校正多重检验后并不显著。所有基于家庭的关联测试均无显著意义(CD p=0.48;按性别校正的 CD 症状数年龄 p=0.91;AD p=0.84;酒精使用障碍 p=0.52)。

结论

与之前的研究结果一致,结果不支持 GABRA2 SNP rs279871 与青少年 AD 之间的关联。我们的结果也不支持 rs279871 与 CD 之间的关联;审查了研究的局限性。

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