Xiang Ruidong, Fang Lingzhao, Liu Shuli, Macleod Iona M, Liu Zhiqian, Breen Edmond J, Gao Yahui, Liu George E, Tenesa Albert, Mason Brett A, Chamberlain Amanda J, Wray Naomi R, Goddard Michael E
Faculty of Veterinary & Agricultural Science, the University of Melbourne, Parkville, VIC 3052, Australia.
Agriculture Victoria, AgriBio, Centre for AgriBiosciences, Bundoora, VIC 3083, Australia.
Cell Genom. 2023 Aug 23;3(10):100385. doi: 10.1016/j.xgen.2023.100385. eCollection 2023 Oct 11.
Many quantitative trait loci (QTLs) are in non-coding regions. Therefore, QTLs are assumed to affect gene regulation. Gene expression and RNA splicing are primary steps of transcription, so DNA variants changing gene expression (eVariants) or RNA splicing (sVariants) are expected to significantly affect phenotypes. We quantify the contribution of eVariants and sVariants detected from 16 tissues (n = 4,725) to 37 traits of ∼120,000 cattle (average magnitude of genetic correlation between traits = 0.13). Analyzed in Bayesian mixture models, averaged across 37 traits, and eVariants and sVariants detected from 16 tissues jointly explain 69.2% (SE = 0.5%) of heritability, 44% more than expected from the same number of random variants. This 69.2% includes an average of 24% from e-/sVariants (14% more than expected). Averaged across 56 lipidomic traits, multi-tissue and e-/sVariants also explain 71.5% (SE = 0.3%) of heritability, demonstrating the essential role of proximal and distal regulatory variants in shaping mammalian phenotypes.
许多数量性状基因座（QTL）位于非编码区域。因此，假定QTL会影响基因调控。基因表达和RNA剪接是转录的主要步骤，所以改变基因表达的DNA变异（e变异）或RNA剪接的DNA变异（s变异）预计会显著影响表型。我们量化了从16种组织（n = 4725）中检测到的e变异和s变异对约120000头牛的37个性状的贡献（性状间遗传相关性的平均幅度 = 0.13）。在贝叶斯混合模型中进行分析，对37个性状进行平均，从16种组织中检测到的e变异和s变异共同解释了69.2%（标准误 = 0.5%）的遗传力，比相同数量的随机变异预期的多44%。这69.2%平均包括来自e/s变异的24%（比预期多14%）。对56个脂质组学性状进行平均，多组织e/s变异也解释了71.5%（标准误 = 0.3%）的遗传力，证明了近端和远端调控变异在塑造哺乳动物表型中的重要作用。
