# Integrated genome-wide association studies, meta-analysis, and Bayesian fine mapping reveal novel quantitative trait loci’s and functional candidate genes for vulva traits in large white pigs

## TL;DR

This study identifies genetic regions and candidate genes influencing vulva traits in Large White pigs, aiding in selective breeding to improve pig production.

## Contribution

Novel QTLs and candidate genes (VIP, NAV3, ESR1) for vulva traits in pigs are identified using GWAS, meta-analysis, and Bayesian fine mapping.

## Key findings

- A significant genomic region on SSC5 is associated with vulva angle scores in Topigs and Canadian Large White pigs.
- A pleiotropic QTL on SSC4 influences both vulva length and width, with a refined 30 kb confidence interval.
- Candidate genes VIP, NAV3, and ESR1 are proposed as regulators of vulva traits based on their biological functions.

## Abstract

The size and angle of the vulva are economically important traits in pig production. Gilts with small or upward-tilted vulva are typically culled directly. Selective breeding aimed at improving vulva traits can enhance the retention rate of replacement gilts. This study aimed to systematically explore the key quantitative trait loci (QTL) and genes influencing vulva traits in Large White pigs using genome-wide association studies (GWAS) and meta-analysis techniques. Data on vulva length (VL), vulva width (VW), and vulva angle scores (VAS) were collected from 2,197 Large White gilts across three distinct populations (313 from PIC, 1,169 from Topigs, and 715 from Canada), with genotyping performed using a 50K single-nucleotide polymorphism (SNP) array. The SNP-chip data were imputed to the whole-genome sequencing (iWGS) level. This study used iWGS data to conduct GWAS, identifying a genomic region (SSC5: 103.04-103.34 Mb) significantly associated with VAS in both the Topigs and Canadian Large White pig populations. The significance of this region was further strengthened through multi-population meta-analysis. The most significant SNP (rs3470833446), identified on chromosome 14 and associated with VW in PIC Large White pigs, explained 16.98% of the phenotypic variation (PVE). Multi-population meta-analysis identified novel significant SNPs associated with VL on SSC4, VW on SSC1, SSC4, and SSC6, and VAS on SSC2 and SSC5. Furthermore, a significant potential pleiotropic QTL (SSC4: 36.42-41.24 Mb) regulating both VL and VW was identified. Bayes fine mapping was employed to determine the confidence intervals for these novel QTLs, with the most refined confidence interval narrowed down to 30 kb (SSC4: 38.73-38.76 Mb for VW, and SSC5: 103.20-103.23 Mb for VAS). Based on the biological functions of the genes, the following were identified as novel regulatory candidate genes for vulva traits: VIP, NAV3, and ESR1. These findings reveal potential key genes and genetic mechanisms influencing vulva traits in pigs, providing a crucial molecular genetic basis for improving pig breeding and reproductive performance.

By identifying novel and pleiotropic QTLs and functional candidate genes associated with vulva size and angle in Large White pigs, this study enhances the understanding of the genetic mechanisms underlying these economically significant traits. The identified QTLs and genes can be leveraged in marker-assisted selection (MAS) and genomic selection (GS) to accelerate genetic advancement in vulva traits among different pig populations.