Genomewide suggestive linkage of opioid dependence to chromosome 14q
Genomewide suggestive linkage of opioid dependence to chromosome 14q
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DOI：
10.1093/hmg/ddm081
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发表时间：
2007-06-01
影响因子：
3.5
通讯作者：
Knowles, James A.
中科院分区：
文献类型：
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作者：
Lachman, Herbert M.;Fann, Cathy S. J.;Knowles, James A.
阿片类药物和其他物质成瘾的遗传倾向作为一种复杂的遗传性状遗传，研究人员正试图利用遗传连锁和关联来描述其特征。我们现在报告一项关于阿片类药物依赖的高密度全基因组连锁研究。我们从一个美沙酮维持治疗的多种族人群中确定了305对符合《精神障碍诊断与统计手册》第四版（DSM - IV）阿片类药物依赖标准的患病同胞对，并使用昂飞公司10K v2芯片对他们的DNA进行基因分型。利用梅林软件（MERLIN）进行的分析确定了14号染色体上的一个区域，其非参数优势对数计分（NPL）为3.30。二次分析表明，该基因座对自我认定为波多黎各裔的亚群相对特异，因为NPL从3.30增加到5.00（高加索裔NPL = 0.05，非裔美国人NPL = 0.15）。14q峰值涵盖了NRXN3基因（神经连接蛋白3），该基因先前已被确定为成瘾的一个潜在候选基因。二次分析还确定了几个性别特异性NPL得分大于2.00的区域。最显著的是在（10q）上的一个峰值，当仅考虑男性时，该峰值从0.90增加到3.22（女性NPL = 0.05）。我们的连锁数据为未来的精细定位遗传分析提示了特定的染色体基因座，并支持种族和性别特异性基因是成瘾易感性基础的这一假设。
The genetic predisposition to addiction to opioids and other substances is transmitted as a complex genetic trait, which investigators are attempting to characterize using genetic linkage and association. We now report a high-density genome-wide linkage study of opioid dependence. We ascertained 305 DSM-IV opioid dependent affected sibling pairs from an ethnically mixed population of methadone maintained subjects and genotyped their DNA using Affymetrix 10K v2 arrays. Analysis with MERLIN identified a region on chromosome 14q with a non-parametric lod (NPL) of 3.30. Secondary analyses indicated that this locus was relatively specific to the self-identified Puerto Rican subset, as the NPL increased from 3.30 to 5.00 (NPLCaucasian = 0.05 and NPLAfrican (Amer.) = 0.15). The 14q peak encompasses the NRXN3 gene (neurexin 3), which was previously identified as a potential candidate gene for addiction. Secondary analyses also identified several regions with gender-specific NPL scores greater than 2.00. The most significant was a peak on (10q) that increased from 0.90 to 3.22 when only males were considered (NPLfemale = 0.05). Our linkage data suggest specific chromosomal loci for future fine-mapping genetic analysis and support the hypothesis that ethnic and gender specific genes underlie addiction susceptibility.