Uhl George R, Liu Qing-Rong, Naiman Daniel
Molecular Neurobiology Branch, NIDA-IRP, NIH, Box 5180, Baltimore, MD 21224, USA.
Trends Genet. 2002 Aug;18(8):420-5. doi: 10.1016/s0168-9525(02)02719-1.
Classical genetic studies suggest strong complex genetic contributions to a predisposition to abuse multiple addictive substances. Until recently, there were no reproducible genome scanning data identifying chromosomal positions likely to contain allelic variants that predispose the carrier to illegal substance addiction. Nominal results of linkage-based genome scanning studies for ethanol and nicotine addictions failed to display much agreement. Our recent data from association-based genome scans for illegal addictions, and reanalyses of previous results now provide a substantial body of converging results. The 15 reproducible chromosomal loci identified here are good candidates to harbor allelic variants that alter human substance abuse vulnerabilities. We discuss several approaches to identifying the specific gene variants that underlie these convergent association and linkage observations, and the impact that these convergent observations should have on understanding important human addictive disorders.
经典遗传学研究表明，多种成瘾性物质滥用倾向具有很强的复杂遗传因素。直到最近，还没有可重复的基因组扫描数据来确定可能包含使携带者易患非法药物成瘾的等位基因变体的染色体位置。基于连锁分析的乙醇和尼古丁成瘾基因组扫描研究的名义结果未能显示出太多一致性。我们最近基于关联分析的非法成瘾基因组扫描数据以及对先前结果的重新分析，现在提供了大量趋同的结果。这里确定的15个可重复的染色体位点很可能包含改变人类药物滥用易感性的等位基因变体。我们讨论了几种识别这些趋同关联和连锁观察结果背后特定基因变体的方法，以及这些趋同观察结果对理解重要人类成瘾性疾病的影响。
