在全基因组关联分析中整合多基因和个体SNP效应

Nick V. L. Serão, J. Beever, Dan B. Faulkner, S. Rodriguez-Zas
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引用次数: 4

摘要

全基因组关联研究(GWAS)缺乏对多基因效应的考虑,可能会使多基因控制的复杂性状的研究结果产生偏差。本研究的目标是开发一种复合gwas模型,在调整多基因效应的同时识别单个snp。建立了基于维持和生长的饲料效率指标——复合性状剩余采食量(RFI)模型。对1387头饲喂不同饲粮的不同品种肉牛的RFI和基因型数据(来自第3、11和24号染色体的5,910个snp)进行了分析,并考虑了加性多基因效应和不加性多基因效应。模型包括饲料日数、日粮日数、品种日数和日粮与品种相互作用的固定效应,当代群效应和加性多基因效应的随机效应。在模型中分别检测到69个和141个snp (p值< 0.01)。第二种模型鉴定出的snp数量较多,证实了忽略多基因性状GWAS中的多基因效应可能会由于连锁不平衡而导致假阳性。采用多基因模型共检测到7个snp (p值< 0.001),其中4个位于第3染色体,2个位于第11染色体,1个位于第24染色体。两个snp,一个来自3号染色体,一个来自11号染色体,位于编码基因区域。我们的结果表明,有必要在复杂的多基因性状中使用包括多基因效应的复合gwas。这些结果表明,将这些标记纳入基因组选择策略可能会加速肉牛饲料效率的遗传改良。
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Integration of polygenic and individual SNP effects in genome-wide association analyses
The lack of consideration of polygenic effects in genome-wide association studies (GWAS) may bias the results in complex traits controlled by multiple genes. The goal of this study is to develop a composite-GWAS model that identifies individual SNPs while adjusting for polygenic effects. The complex trait residual feed intake (RFI), an indicator of the feed efficiency based on maintenance and growth, was modeled. RFI and genotypic data (5,910 SNPs from chromosomes 3, 11 and 24) from 1,387 steers from different breeds and receiving different diets were analyzed, with and without the additive polygenic effect. The model included the fixed effects of days of feed, diet, breed and interaction between diet and breed, and the random effects of contemporary group and additive polygenic effect. A total of 69 and 141 SNPs were detected (P-value < 0.01) with the model including and excluding polygenic effects, respectively. The higher number of SNPs identified by the second model confirms that ignoring polygenic effects in GWAS of multi-gene traits can lead to false positives due to linkage disequilibrium. Seven SNPs (P-value < 0.001), four in chromosomes 3, two in chromosome 11 and one in chromosome 24, were detected using the polygenic model. Two SNPs, one from chromosome 3 and one from 11 are located within coding gene regions. Our results demonstrate the need to use composite-GWAS that include polygenic effects in complex multi-gene traits. These results indicated that the genetic improvement of feed efficiency in beef cattle may be accelerated by the incorporation of these markers in genomic selection strategies.
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