Sheet Sunirmal, Krishnamoorthy Srikanth, Cha Jihye, Choi Soyoung, Choi Bong-Hwan
Animal Genome & Bioinformatics, National Institute of Animal Science, RDA, Wanju 55365, Korea.
Animals (Basel). 2020 Nov 9;10(11):2071. doi: 10.3390/ani10112071.
The present study aimed to identify causative loci and genes enriched in pathways associated with canine obesity using a genome-wide association study (GWAS). The GWAS was first performed to identify candidate single-nucleotide polymorphisms (SNPs) associated with obesity and obesity-related traits including body weight and blood sugar in 18 different breeds of 153 dogs. A total of 10 and 2 SNPs were found to be significantly ( < 3.74 × 10) associated with body weight and blood sugar, respectively. None of the SNPs were identified to be significantly associated with obesity trait. We subsequently followed up the GWAS analysis with gene-set enrichment and pathway analyses. A gene-set with 1057, 1409, and 1243 SNPs annotated to 449, 933 and 820 genes for obesity, body weight, and blood sugar, respectively was created by sub-setting the GWAS result at a threshold of < 0.01 for the gene-set enrichment analysis. In total, 84 GO and 21 KEGG pathways for obesity, 114 GO and 44 KEGG pathways for blood sugar, 120 GO and 24 KEGG pathways for body weight were found to be enriched. Among the pathways and GO terms, we highlighted five enriched pathways (Wnt signaling pathway, adherens junction, pathways in cancer, axon guidance, and insulin secretion) and seven GO terms (fat cell differentiation, calcium ion binding, cytoplasm, nucleus, phospholipid transport, central nervous system development, and cell surface) that were found to be shared among all the traits. Our data provide insights into the genes and pathways associated with obesity and obesity-related traits.
本研究旨在通过全基因组关联研究（GWAS）确定与犬类肥胖相关的致病基因座和富集于相关通路的基因。首先进行GWAS，以确定153只狗的18个不同品种中与肥胖及肥胖相关性状（包括体重和血糖）相关的候选单核苷酸多态性（SNP）。分别发现共有10个和2个SNP与体重和血糖显著相关（<3.74×10）。未发现SNP与肥胖性状显著相关。随后，我们对GWAS分析进行了基因集富集和通路分析。通过将GWAS结果设定为<0.01的阈值进行基因集富集分析，分别创建了一个基因集，其中1057、1409和1243个SNP分别注释到449、933和820个与肥胖、体重和血糖相关的基因。总共发现84个GO和21个KEGG通路与肥胖相关，114个GO和44个KEGG通路与血糖相关，120个GO和24个KEGG通路与体重相关。在这些通路和GO术语中，我们重点关注了五个富集通路（Wnt信号通路、黏着连接、癌症通路、轴突导向和胰岛素分泌）和七个GO术语（脂肪细胞分化、钙离子结合、细胞质、细胞核、磷脂转运、中枢神经系统发育和细胞表面），这些在所有性状中均有发现。我们的数据为与肥胖及肥胖相关性状的基因和通路提供了见解。
