Genetic improvement of wool and growth traits is a major goal in the sheep industry, but their underlying genetic architecture remains elusive. To improve our understanding of these mechanisms, we conducted a weighted single-step genome-wide association study (WssGWAS) and then integrated the results with large-scale transcriptome data for five wool traits and one growth trait in Merino sheep: mean fibre diameter (MFD), coefficient of variation of the fibre diameter (CVFD), crimp number (CN), mean staple length (MSL), greasy fleece weight (GFW), and live weight (LW). Our dataset comprised 7135 individuals with phenotype data, among which 1217 had high-density (HD) genotype data (n = 372,534). The genotypes of 707 of these animals were imputed from the Illumina Ovine single nucleotide polymorphism (SNP) 54 BeadChip to the HD Array. The heritability of these traits ranged from 0.05 (CVFD) to 0.36 (MFD), and between-trait genetic correlations ranged from − 0.44 (CN vs. LW) to 0.77 (GFW vs. LW). By integrating the GWAS signals with RNA-seq data from 500 samples (representing 87 tissue types from 16 animals), we detected tissues that were relevant to each of the six traits, e.g. liver, muscle and the gastrointestinal (GI) tract were the most relevant tissues for LW, and leukocytes and macrophages were the most relevant cells for CN. For the six traits, 54 quantitative trait loci (QTL) were identified covering 81 candidate genes on 21 ovine autosomes. Multiple candidate genes showed strong tissue-specific expression, e.g. BNC1 (associated with MFD) and CHRNB1 (LW) were specifically expressed in skin and muscle, respectively. By conducting phenome-wide association studies (PheWAS) in humans, we found that orthologues of several of these candidate genes were significantly (FDR < 0.05) associated with similar traits in humans, e.g. BNC1 was significantly associated with MFD in sheep and with hair colour in humans, and CHRNB1 was significantly associated with LW in sheep and with body mass index in humans. Our findings provide novel insights into the biological and genetic mechanisms underlying wool and growth traits, and thus will contribute to the genetic improvement and gene mapping of complex traits in sheep.

中文翻译：

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将单步全基因组关联研究与多组织转录组分析相结合，提供了对绵羊羊毛和体重性状遗传基础的新见解

羊毛和生长特性的遗传改良是养羊业的一个主要目标，但其潜在的遗传结构仍然难以捉摸。为了提高我们对这些机制的理解，我们进行了加权单步全基因组关联研究 (WssGWAS)，然后将结果与美利奴绵羊的五个羊毛性状和一个生长性状的大规模转录组数据进行整合：平均纤维直径（ MFD)、纤维直径变异系数 (CVFD)、卷曲数 (CN)、平均纤维长度 (MSL)、含脂羊毛重量 (GFW) 和活重 (LW)。我们的数据集包含 7135 名具有表型数据的个体，其中 1217 名具有高密度 (HD) 基因型数据 (n = 372,534)。其中 707 只动物的基因型从 Illumina Ovine 单核苷酸多态性 (SNP) 54 BeadChip 推算到 HD Array。这些性状的遗传力范围为 0.05 (CVFD) 至 0.36 (MFD)，性状间遗传相关性范围为 - 0.44 (CN vs. LW) 至 0.77 (GFW vs. LW)。通过将 GWAS 信号与来自 500 个样本（代表 16 只动物的 87 种组织类型）的 RNA-seq 数据相结合，我们检测到与六个特征中的每一个相关的组织，例如肝脏、肌肉和胃肠 (GI) 道是最重要的。 LW 的相关组织，白细胞和巨噬细胞是 CN 最相关的细胞。对于这六个性状，鉴定了 54 个数量性状位点 (QTL)，覆盖了 21 个绵羊常染色体上的 81 个候选基因。多个候选基因表现出强烈的组织特异性表达，例如BNC1（与MFD相关）和CHRNB1（LW）分别在皮肤和肌肉中特异性表达。通过在人类中进行全表型关联研究 (PheWAS)，我们发现其中几个候选基因的直系同源物与人类的相似特征显着相关（FDR < 0.05），例如 BNC1 与绵羊的 MFD 和头发颜色显着相关在人类中，CHRNB1 与绵羊的 LW 和人类的体重指数显着相关。我们的发现为羊毛和生长性状背后的生物学和遗传机制提供了新的见解，从而有助于绵羊复杂性状的遗传改良和基因定位。CHRNB1 与绵羊的 LW 和人类的体重指数显着相关。我们的发现为羊毛和生长性状背后的生物学和遗传机制提供了新的见解，从而有助于绵羊复杂性状的遗传改良和基因定位。CHRNB1 与绵羊的 LW 和人类的体重指数显着相关。我们的发现为羊毛和生长性状背后的生物学和遗传机制提供了新的见解，从而有助于绵羊复杂性状的遗传改良和基因定位。