BACKGROUND While genome-wide association studies (GWAS) of multiple myeloma (MM) have identified variants at 23 regions influencing risk, the genes underlying these associations are largely unknown. To identify candidate causal genes at these regions and search for novel risk regions, we performed a multi-tissue transcriptome-wide association study (TWAS). RESULTS GWAS data on 7319 MM cases and 234,385 controls was integrated with Genotype-Tissue Expression Project (GTEx) data assayed in 48 tissues (sample sizes, N = 80-491), including lymphocyte cell lines and whole blood, to predict gene expression. We identified 108 genes at 13 independent regions associated with MM risk, all of which were in 1 Mb of known MM GWAS risk variants. Of these, 94 genes, located in eight regions, had not previously been considered as a candidate gene for that locus. CONCLUSIONS Our findings highlight the value of leveraging expression data from multiple tissues to identify candidate genes responsible for GWAS associations which provide insight into MM tumorigenesis. Among the genes identified, a number have plausible roles in MM biology, notably APOBEC3C, APOBEC3H, APOBEC3D, APOBEC3F, APOBEC3G, or have been previously implicated in other malignancies. The genes identified in this TWAS can be explored for follow-up and validation to further understand their role in MM biology.

中文翻译：

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多发性骨髓瘤的全转录组关联研究确定了候选易感基因。

背景技术虽然多发性骨髓瘤（MM）的全基因组关联研究（GWAS）已经在影响风险的23个区域鉴定了变体，但是这些关联的基础基因在很大程度上是未知的。为了确定这些区域的候选病因基因并寻找新的危险区域，我们进行了一次多组织转录组范围内的关联研究（TWAS）。结果将7319例MM病例和234,385例对照的GWAS数据与基因型组织表达计划（GTEx）数据进行了整合，在包括淋巴细胞细胞系和全血在内的48个组织（样本大小，N = 80-491）中进行了分析，以预测基因表达。我们在与MM风险相关的13个独立区域中鉴定了108个基因，所有这些基因都在1 Mb的已知MM GWAS风险变异中。其中，位于八个区域的94个基因以前未被认为是该基因座的候选基因。结论我们的发现强调了利用来自多个组织的表达数据来鉴定与GWAS关联有关的候选基因的价值，这些关联为MM肿瘤发生提供了见识。在鉴定出的基因中，许多在MM生物学中具有合理的作用，特别是APOBEC3C，APOBEC3H，APOBEC3D，APOBEC3F，APOBEC3G，或者以前与其他恶性肿瘤有关。可以探索在该TWAS中鉴定的基因，以进行跟踪和验证，以进一步了解其在MM生物学中的作用。或以前曾与其他恶性肿瘤有关。可以探索在该TWAS中鉴定的基因，以进行跟踪和验证，以进一步了解其在MM生物学中的作用。或以前曾与其他恶性肿瘤有关。可以探索该TWAS中鉴定的基因以进行跟踪和验证，以进一步了解其在MM生物学中的作用。