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Genome-wide linkage analysis of heroin dependence in Han Chinese: Results from Wave Two of a multi-stage study

机译：中国汉族人对海洛因依赖的全基因组连锁分析：第二阶段多阶段研究的结果

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Previously we reported the results of Wave One of a genome-wide search for heroin dependence susceptibility loci in Han Chinese families from Yunnan Province, China, near Asia’s “Golden Triangle”. Our initial analysis of 194 independent affected sibling-pairs from 192 families identified two regions with nonparametric linkage (NPL) Z-scores greater than 2.0, which were suggestive of linkage. Presently we have supplemented our sample with additional individuals and families, bringing the total number of genotyped individuals to 1513 and the number of independent sibling-pairs to 397. Upon repeating our analyses with this larger sample, we found that the evidence for linkage at our most strongly implicated locus from Wave One (marker D17S1880; 53.4 cM on 17q11.2; NPL Z = 2.36; uncorrected p = 0.009) was completely abolished (Z = -1.13; p = 0.900). In contrast, the evidence for linkage at the second-most strongly implicated locus from Wave One (D4S1644; 143.3 cM on 4q31.21; NPL Z = 2.19; uncorrected p = 0.014) increased in its magnitude and significance (Z = 2.64; uncorrected p = 0.004), becoming the most strongly implicated locus overall in our full sample. Other loci on chromosomes 1, 2, 4, 12, 16, and X also displayed nominally significant evidence for linkage (p ≤ 0.05). These loci appear to be entirely distinct from opioid-linked loci reported by other groups; however, meta-analyses of all available linkage data may reveal common sites of interest and promising candidate genes that can be further evaluated as risk factors for the illness.
机译：此前，我们报道了第一波研究的结果，该研究是在亚洲“金三角”附近的中国云南汉族家庭中对海洛因依赖性易感基因座进行的全基因组搜索。我们对来自192个家庭的194个独立受影响兄弟姐妹对的初步分析确定了两个区域的非参数连锁（NPL）Z得分均大于2.0，这表明存在连锁关系。目前，我们在样本中增加了其他个体和家庭，使基因型个体总数达到1513，独立同胞对的总数达到397。在对这个更大的样本进行重复分析之后，我们发现在我们的样本中存在连锁的证据完全废除了第一波的最相关位点（标记D17S1880； 17q11.2上的53.4 cM； NPL Z = 2.36；未校正的p = 0.009）（Z = -1.13； p = 0.900）。相反，来自第一波的第二紧密相关位点连锁的证据（D4S1644； 4q31.21上为143.3 cM； NPL Z = 2.19；未校正p = 0.014）在数量级和重要性上都增加了（Z = 2.64；未校正）。 p = 0.004），成为我们整个样本中牵连性最强的基因座。染色体1、2、4、12、16和X上的其他基因座也显示出名义上重要的连锁证据（p≤0.05）。这些基因座似乎与其他群体报告的与阿片类药物相关的基因座完全不同。然而，所有可用连锁数据的荟萃分析都可能揭示出共同感兴趣的位点和有希望的候选基因，这些基因可以进一步评估为疾病的危险因素。

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