Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, Connecticut, United States of America.
PLoS One. 2011 Jan 27;6(1):e16002. doi: 10.1371/journal.pone.0016002.
Substance dependence or addiction is a complex environmental and genetic disorder that results in serious health and socio-economic consequences. Multiple substance dependence categories together, rather than any one individual addiction outcome, may explain the genetic variability of such disorder. In our study, we defined a composite substance dependence phenotype derived from six individual diagnoses: addiction to nicotine, alcohol, marijuana, cocaine, opiates or other drugs as a whole. Using data from several genomewide case-control studies, we identified a strong (Odds ratio = 1.77) and significant (p-value = 7E-8) association signal with a novel gene, PBX/knotted 1 homeobox 2 (PKNOX2), on chromosome 11 with the composite phenotype in European-origin women. The association signal is not as significant when individual outcomes for addiction are considered, or in males or African-origin population. Our findings underscore the importance of considering multiple addiction types and the importance of considering population and gender stratification when analyzing data with heterogeneous population.
物质依赖或成瘾是一种复杂的环境和遗传疾病，会导致严重的健康和社会经济后果。多种物质依赖类别一起，而不是任何一种个体成瘾结果，可能解释了这种疾病的遗传可变性。在我们的研究中，我们定义了一个复合物质依赖表型，由六个个体诊断组成：尼古丁、酒精、大麻、可卡因、阿片类药物或其他药物成瘾。使用来自多个全基因组病例对照研究的数据，我们在欧洲血统女性的复合表型中发现了一个与新型基因 PBX/knotted 1 homeobox 2 (PKNOX2) 相关的强（比值比 = 1.77）和显著（p 值 = 7E-8）关联信号。当考虑成瘾的个体结果或男性或非洲血统人群时，关联信号就不那么显著了。我们的研究结果强调了考虑多种成瘾类型的重要性，以及在分析具有异质人群的数据时考虑人群和性别分层的重要性。
