A bivariate mann-whitney approach for unraveling genetic variants and interactions contributing to comorbidity.
A bivariate mann-whitney approach for unraveling genetic variants and interactions contributing to comorbidity.
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一种双变量曼惠特尼方法，用于揭示导致合并症的遗传变异和相互作用。
DOI：
10.1002/gepi.21709
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发表时间：
2013
影响因子：
2.1
通讯作者：
Lu,Qing
中科院分区：
文献类型：
--
作者：
Wen,Yalu;Schaid,DanielJ;Lu,Qing
尽管复杂疾病(如药物依赖综合征)之间的共病已有很好的文献记载，但导致共病的遗传变异仍在很大程度上尚不清楚。基因变异及其相互作用的发现有助于了解合并症的潜在病理生理和病因过程，并促进对合并症的有效治疗。出于这个原因，发现促进共病发展的遗传变异的研究是高度优先的研究项目，正如目前正在进行的行为遗传学研究所表明的那样。这些研究的产量可以通过采用新的统计方法来提高，能够考虑多种遗传变异和可能的相互作用。为此，我们提出了一种双变量Mann-Whitney(BMW)方法来揭示导致共病的遗传变异和相互作用，以及每种共病条件下独有的遗传变异和相互作用。通过模拟，我们发现宝马在各种潜在疾病和共病模型中的表现优于两种常用的方法。我们进一步将宝马应用于成瘾研究：遗传学和环境的数据集，调查了184个已知的尼古丁依赖(ND)和酒精依赖(AD)单核苷酸多态(SNPs)对ND和AD共病的贡献。分析发现了一个来自CHRNA5的候选SNP，rs16969968，与ND和AD都相关，并在一个独立的数据集中重复了发现，AP值为1.06×10-03。
Although comorbidity among complex diseases (e.g., drug dependence syndromes) is well documented, genetic variants contributing to the comorbidity are still largely unknown. The discovery of genetic variants and their interactions contributing to comorbidity will likely shed light on underlying pathophysiological and etiological processes, and promote effective treatments for comorbid conditions. For this reason, studies to discover genetic variants that foster the development of comorbidity represent high‐priority research projects, as manifested in the behavioral genetics studies now underway. The yield from these studies can be enhanced by adopting novel statistical approaches, with the capacity of considering multiple genetic variants and possible interactions. For this purpose, we propose a bivariate Mann‐Whitney (BMW) approach to unravel genetic variants and interactions contributing to comorbidity, as well as those unique to each comorbid condition. Through simulations, we found BMW outperformed two commonly adopted approaches in a variety of underlying disease and comorbidity models. We further applied BMW to datasets from theStudy of Addiction: Genetics and Environment, investigating the contribution of 184 known nicotine dependence (ND) and alcohol dependence (AD) single nucleotide polymorphisms (SNPs) to the comorbidity of ND and AD. The analysis revealed a candidate SNP fromCHRNA5, rs16969968, associated with both ND and AD, and replicated the findings in an independent dataset with aP‐value of 1.06 × 10–03.
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影响因子：
--
作者：
Treutlein, Jens;Cichon, Sven;Ridinger, Monika;Wodarz, Norbert;Soyka, Michael;Zill, Peter;Maier, Wolfgang;Moessner, Rainald;Gaebel, Wolfgang;Dahmen, Norbert;Fehr, Christoph;Scherbaum, Norbert;Steffens, Michael;Ludwig, Kerstin U.;Frank, Josef;Wichmann, H. Erich;Schreiber, Stefan;Dragano, Nico;Sommer, Wolfgang H.;Leonardi-Essmann, Fernando;Lourdusamy, Anbarasu;Gebicke-Haerter, Peter;Wienker, Thomas F.;Sullivan, Patrick F.;Noethen, Markus M.;Kiefer, Falk;Spanagel, Rainer;Mann, Karl;Rietschel, Marcella
通讯作者：
Rietschel, Marcella
影响因子：
--
作者：
True, WR;Xian, H;Tsuang, M
通讯作者：
Tsuang, M
影响因子：
7.6
作者：
Riala, K;Hakko, H;Räsänen, P
通讯作者：
Räsänen, P
影响因子：
4.7
作者：
Clark, A;Lindgren, S;Little, HJ
通讯作者：
Little, HJ
影响因子：
3.5
作者：
Saccone, Scott F.;Hinrichs, Anthony L.;Bierut, Laura Jean
通讯作者：
Bierut, Laura Jean