Ordered subsets linkage analysis of antisocial behavior in substance use disorder among participants in the Collaborative Study on the Genetics of Alcoholism.
Ordered subsets linkage analysis of antisocial behavior in substance use disorder among participants in the Collaborative Study on the Genetics of Alcoholism.
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DOI：
10.1002/ajmg.b.30771
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发表时间：
2008-10-05
期刊：
影响因子：
--
通讯作者：
Participants in the Collaborative Study on the Genetics of Alcoholism
中科院分区：
文献类型：
--
作者：
Jacobson KC;Beseler CL;Lasky-Su J;Faraone SV;Glatt SJ;Kremen WS;Lyons MJ;Tsuang MT;Participants in the Collaborative Study on the Genetics of Alcoholism
复杂疾病如物质使用障碍（SUD）中的异源性降低了检测联系的能力，并使其他人群的研究结果不太可能复制。因此，关键是要完善的表型和使用的方法，占家庭之间的遗传异质性。SUD被操作为酒精和/或五种非法物质中任何一种的滥用或依赖的诊断。在Merlin中使用受影响的同胞设计对来自酒精中毒遗传学合作研究的241个扩展系谱家庭进行全基因组连锁分析。使用FLOSS的有序子集分析（OSA）试图通过根据儿童和成人反社会行为的密度对家庭进行排名来增加样本的同质性，为每个家庭子集的每个染色体产生新的最大非参数Lod（NPL）分数。在OSA之前，在8号和17号染色体上发现了一定的连锁证据。虽然NPL评分的变化没有统计学意义，但OSA揭示了7号染色体上靠近标记D 7S 1795和D 7S 821的连锁的可能证据。在染色体2、3、5、9和14上也观察到NPL评分>3.0。然而，在这些后一个子集中用于连锁的家族数量可能太少而没有意义。结果提供了一些证据，OSA的能力，以减少遗传异质性，并进一步支持7号染色体作为一个可能的位置，以寻找各种SUD相关过程的基因。尽管如此，在其他样品中复制这些结果是必不可少的。
Heterogeneity in complex diseases such as Substance Use Disorder (SUD) reduces the power to detect linkage and makes replication of findings in other populations unlikely. It is therefore critical to refine the phenotype and use methods that account for genetic heterogeneity between families. SUD was operationalized as diagnosis of abuse or dependence to alcohol and/or any one of five illicit substances. Whole-genome linkage analysis of 241 extended pedigree families from the Collaborative Study on the Genetics of Alcoholism was performed in Merlin using an affected sibship design. An Ordered Subsets Analysis (OSA) using FLOSS sought to increase the homogeneity of the sample by ranking families by their density of childhood and adult antisocial behaviors, producing new maximum Nonparametric Lod (NPL) scores on each chromosome for each subset of families. Prior to OSA, modest evidence for linkage was found on chromosomes 8 and 17. Although changes in NPL scores were not statistically significant, OSA revealed possible evidence of linkages on chromosome 7, near markers D7S1795 and D7S821. NPL scores >3.0 were also observed on chromosomes 2, 3, 5, 9, and 14. However, the number of families used in these latter subsets for linkage may be too small to be meaningful. Results provide some evidence for the ability of OSA to reduce genetic heterogeneity, and add further support to chromosome 7 as a possible location to search for genes related to various SUD related processes. Nonetheless, replication of these results in other samples is essential.
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影响因子：
56.9
作者：
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