BACKGROUND Linking human genetics and brain imaging data is extremely challenging, among other reasons because both fields suffer from multiple comparison problems. NEW METHOD ProcessGeneLists (PGL) links genetics and human brain imaging by using genes associated with a disease and calculating a normalized mRNA expression average of those genes in each brain region. Brain regions in which those genes are most co-expressed become regions of interest (ROIs) to perform brain imaging in participants with and without the disease, decreasing multiple comparisons. Once a region is identified as "imaging-relevant", the genes most responsible for that ROI being highlighted can be genotyped in the imaged sample. This allows to re-analyze imaging data under the light of likely relevant genetics, to study possible brain imaging/gene variant interactions. RESULTS As proof-of-concept, we created two lists of genes expressed in the habenula and the striatum, to verified that PGL would highlight those regions. Next, we used a list of genes likely important in alcohol abuse from the literature, which identified several brain regions previously associated with alcohol abuse such as the striatum, habenula, and hippocampus. COMPARISON WITH EXISTING METHODS To our knowledge there is no current method to obtain brain regions of interest from genetics data. CONCLUSIONS Genetics typically asks "which genes are associated with a disease?" while human brain imaging typically asks "which brain regions are associated with a disease?" PGL asks "which genes, via modulation within specific brain regions, are found to be associated with a disease?".

中文翻译：

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过程基因列表：一种将遗传学与人脑成像联系起来的方法。

背景技术除其他原因之外，将人类遗传学和脑成像数据联系起来是极具挑战性的，因为两个领域都遭受多个比较问题。新方法ProcessGeneLists（PGL）通过使用与疾病相关的基因并计算每个大脑区域中那些基因的标准化mRNA表达平均值，将遗传学与人脑成像联系起来。这些基因最共表达的大脑区域成为目标区域（ROI），可以在有或没有疾病的参与者中进行大脑成像，从而减少了多次比较。一旦一个区域被识别为“影像相关”，就可以在成像样本中对导致高亮显示ROI的最负责的基因进行基因分型。这样就可以根据可能的相关遗传学重新分析成像数据，研究可能的大脑成像/基因变异相互作用。结果作为概念验证，我们创建了在哈贝努拉和纹状体中表达的两个基因列表，以验证PGL会突出显示这些区域。接下来，我们从文献中使用了可能对酗酒重要的基因列表，该基因鉴定了先前与酗酒有关的几个大脑区域，例如纹状体，哈贝努拉和海马。与现有方法的比较据我们所知，目前尚无从遗传学数据中获得感兴趣的大脑区域的方法。结论遗传学通常会问“哪些基因与疾病有关？” 而人脑成像通常会问“哪些脑区域与疾病有关？” PGL询问“哪些基因通过特定大脑区域内的调节，