Multi-trait GWAS using imputed high-density genotypes from whole-genome sequencing identifies genes associated with body traits in Nile tilapia

Abstract

Background: Body traits are generally controlled by several genes in vertebrates (i.e. polygenes), which in turn make them difficult to identify through association mapping. Increasing the power of association studies by combining approaches such as genotype imputation and multi-trait analysis improves the ability to detect quantitative trait loci associated with polygenic traits, such as body traits.

Results: A multi-trait genome-wide association study (mtGWAS) was performed to identify quantitative trait loci (QTL) and genes associated with body traits in Nile tilapia (Oreochromis niloticus) using genotypes imputed to whole-genome sequences (WGS). To increase the statistical power of mtGWAS for the detection of genetic associations, summary statistics from single-trait genome-wide association studies (stGWAS) for eight different body traits recorded in 1309 animals were used. The mtGWAS increased the statistical power from the original sample size from 13 to 44%, depending on the trait analyzed. The better resolution of the WGS data, combined with the increased power of the mtGWAS approach, allowed the detection of significant markers which were not previously found in the stGWAS. Some of the lead single nucleotide polymorphisms (SNPs) were found within important functional candidate genes previously associated with growth-related traits in other terrestrial species. For instance, we identified SNP within the α1,6-fucosyltransferase (FUT8), solute carrier family 4 member 2 (SLC4A2), A disintegrin and metalloproteinase with thrombospondin motifs 9 (ADAMTS9) and heart development protein with EGF like domains 1 (HEG1) genes, which have been associated with average daily gain in sheep, osteopetrosis in cattle, chest size in goats, and growth and meat quality in sheep, respectively.

Conclusions: The high-resolution mtGWAS presented here allowed the identification of significant SNPs, linked to strong functional candidate genes, associated with body traits in Nile tilapia. These results provide further insights about the genetic variants and genes underlying body trait variation in cichlid fish with high accuracy and strong statistical support.

Keywords: Body traits; Genome-wide association study; Genotype imputation; Multi-trait; Oreochromis niloticus; Quantitative trait loci.

Fig. 1

Correlation of SNP effects (standard error) among eight body traits in Nile tilapia. ADG: average daily gain (g); BWH: body weight at harvest (g); WW: waste weight (g); HW: head weight (g); HON: gutted head-on weight (g); BLH: body length at harvest (cm); FW: fillet weight (g); FY: fillet yield (%)

Fig. 2

Manhattan plot for multi-trait GWAS (mtGWAS) for eight body traits in Nile tilapia. Manhattan plots of SNPs associated with: a Average daily gain. b Body weight at harvest. c Waste weight. d Head weight. e Gutted head-on weight. f Body length at harvest. g Fillet weight. h Fillet yield. The x-axis presents genomic coordinates along chromosomes 1–23 in Nile tilapia. On the y-axis the negative logarithm of the SNPs associated p-value is displayed. The dashed black line represents the genome-wide significance threshold after Bonferroni correction (−log₁₀ (p-value > 7.21e-8)