PCA-Based Multiple-Trait GWAS Analysis: A Powerful Model for Exploring Pleiotropy

• Main Authors: Wengang Zhang, Xue Gao, Xinping Shi, Bo Zhu, Zezhao Wang, Huijiang Gao, Lingyang Xu, Lupei Zhang, Junya Li, Yan Chen
• Format: Article
• Language: English
• Published: MDPI AG 2018-12-01
• Series: Animals
• Subjects: genome-wide association study; principal component analysis; multiple-trait; pleiotropy; <i>MCHR2</i>
• Online Access: https://www.mdpi.com/2076-2615/8/12/239

Principal component analysis (PCA) is a potential approach that can be applied in multiple-trait genome-wide association studies (GWAS) to explore pleiotropy, as well as increase the power of quantitative trait loci (QTL) detection. In this study, the relationship of test single nucleotide polymorphisms (SNPs) was determined between single-trait GWAS and PCA-based GWAS. We found that the estimated pleiotropic quantitative trait nucleotides (QTNs) <inline-formula> <math display="inline"> <semantics> <mrow> <mover accent="true"> <mrow> <msup> <mi>β</mi> <mo>*</mo> </msup> </mrow> <mo stretchy="true">^</mo> </mover> </mrow> </semantics> </math> </inline-formula> were in most cases larger than the single-trait model estimations (<inline-formula> <math display="inline"> <semantics> <mrow> <mover accent="true"> <mrow> <msub> <mi>β</mi> <mn>1</mn> </msub> </mrow> <mo stretchy="true">^</mo> </mover> </mrow> </semantics> </math> </inline-formula> and <inline-formula> <math display="inline"> <semantics> <mrow> <mover accent="true"> <mrow> <msub> <mi>β</mi> <mn>2</mn> </msub> </mrow> <mo stretchy="true">^</mo> </mover> </mrow> </semantics> </math> </inline-formula>). Analysis using the simulated data showed that PCA-based multiple-trait GWAS has improved statistical power for detecting QTL compared to single-trait GWAS. For the minor allele frequency (MAF), when the MAF of QTNs was greater than 0.2, the PCA-based model had a significant advantage in detecting the pleiotropic QTNs, but when its MAF was reduced from 0.2 to 0, the advantage began to disappear. In addition, as the linkage disequilibrium (LD) of the pleiotropic QTNs decreased, its detection ability declined in the co-localization effect model. Furthermore, on the real data of 1141 Simmental cattle, we applied the PCA model to the multiple-trait GWAS analysis and identified a QTL that was consistent with a candidate gene, <i>MCHR2</i>, which was associated with presoma muscle development in cattle. In summary, PCA-based multiple-trait GWAS is an efficient model for exploring pleiotropic QTNs in quantitative traits.