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Article

Genome-Wide Association Study on Reproductive Traits Using Imputation-Based Whole-Genome Sequence Data in Yorkshire Pigs

1
Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, Laboratory of Animal Fat Deposition & Muscle Development, College of Animal Science and Technology, Northwest A&F University, Xianyang 712100, China
2
National Engineering Laboratory for Animal Breeding, Laboratory of Animal Genetics, Breeding and Reproduction, Ministry of Agriculture, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Genes 2023, 14(4), 861; https://doi.org/10.3390/genes14040861
Submission received: 10 March 2023 / Revised: 28 March 2023 / Accepted: 31 March 2023 / Published: 2 April 2023
(This article belongs to the Special Issue Genetics and Genomics of Pig Breeding)

Abstract

:
Reproductive traits have a key impact on production efficiency in the pig industry. It is necessary to identify the genetic structure of potential genes that influence reproductive traits. In this study, a genome-wide association study (GWAS) based on chip and imputed data of five reproductive traits, namely, total number born (TNB), number born alive (NBA), litter birth weight (LBW), gestation length (GL), and number of weaned (NW), was performed in Yorkshire pigs. In total, 272 of 2844 pigs with reproductive records were genotyped using KPS Porcine Breeding SNP Chips, and then chip data were imputed to sequencing data using two online software programs: the Pig Haplotype Reference Panel (PHARP v2) and Swine Imputation Server (SWIM 1.0). After quality control, we performed GWAS based on chip data and the two different imputation databases by using fixed and random model circulating probability unification (FarmCPU) models. We discovered 71 genome-wide significant SNPs and 25 potential candidate genes (e.g., SMAD4, RPS6KA2, CAMK2A, NDST1, and ADCY5). Functional enrichment analysis revealed that these genes are mainly enriched in the calcium signaling pathway, ovarian steroidogenesis, and GnRH signaling pathways. In conclusion, our results help to clarify the genetic basis of porcine reproductive traits and provide molecular markers for genomic selection in pig breeding.

1. Introduction

The reproductive performance of pigs plays a key role in the pig industry. Improving the reproductive performance of sows can lead to higher economic benefits for pig farms. However, reproductive traits are low-heritability traits, and their genetic structure is much more complex [1]. Therefore, it is difficult to improve these traits more rapidly using traditional breeding methods. With the development of molecular breeding technology, marker-assisted selection (MAS) and genomic selection (GS) have become effective ways to improve pig breeding efficiency [2].
In recent years, to complete genomic screening for trait-associated variants, genome-wide association studies (GWASs) have been widely applied to find quantitative trait loci (QTL) in economic traits [3]. Thus far, 35,384 QTLs have been identified in pigs according to pigQTLdb, of which 3315 QTLs are associated with reproduction (https://www.animalgenome.org/cgi-bin/QTLdb/SS/summary, 25 April 2022). In pigs, GWAS has identified numerous SNPs significantly associated with growth traits [4,5], meat quality [6,7], feed efficiency [8,9], semen traits [10,11], coat color [12,13], genetic defects [14,15], disease susceptibility [16,17], and microbial phenotypes [18]. However, most of them were genotyped based on SNP microarrays, and the density of markers is a key factor affecting GWAS efficiency [19]. With the development of sequencing technology and its increasingly low cost, many researchers have used sequencing or resequencing to perform relevant studies [20,21,22]. However, the sequencing or resequencing of large population samples is too costly and remains an inefficient strategy. Genotype imputation is an effective strategy in GWAS [23], which has been widely used in human genetics research, such as HapMap [24] and the 1000 Genomes Project [25]. It can increase the total number and density of SNPs used for association analysis and provide the opportunity to discover new potential genes.
In our study, we performed GWAS using two different genotype imputation databases and identified genetic variants related to five reproductive traits in large white pigs.

2. Materials and Methods

2.1. Ethics Statement

All ear tissue sample collection procedures were approved by the Institutional Animal Care and Use Committee of the Northwest A & F University (approval number: NWAFU-314021167).

2.2. Animals and Phenotypes

The pig population was uniformly reared at the core breeding farm of Zhumei Group Limited (Zhumadian City, China). Briefly, we collected breeding information and lineage records of large white pigs from 2011 to 2019 at this farm. There were 3733 pigs with complete pedigrees, and pedigrees could be traced back three generations. A total of 10,206 reproduction records of 2844 pigs were collected. The phenotype records included parity (including 8 levels: 1, 2, 3, 4, 5, 6, 7, or 8 or higher parity number), herd-year-season, and five reproductive traits. Five reproductive phenotypes, namely, total number born (TNB), number born alive (NBA), litter birth weight (LBW), gestation length (GL), and number of weaned (NW), were chosen for the next analysis. Table 1 presents the descriptive statistics of the five traits. Apart from GL, the other four traits had coefficients of variation above 25%.

2.3. Genotyping and Genotype Imputation

In this study, KPS Porcine Breeding 50K Chip v1 (Compass Biotechnology, Beijing, China), which contains 51,315 SNPs, was used to genotype 272 individuals of the total 2844 pigs with phenotype records. Then, quality control was performed by only keeping SNPs with MAF > 0.05, SNP call rate > 95%, individual call rate > 95%, and HWE > 1 × 10−6 using the PLINK software (v1.90) [26]. A total of 31,174 SNPs and 271 animals were retained for further GWAS. To improve the marker density, imputation was performed using two online software programs: the Pig Haplotype Reference Panel (PHARP v2) (http://alphaindex.zju.edu.cn/PHARP/index.php/, accessed on 21 October 2022) [27] and Swine Imputation Server (SWIM 1.0) (https://quantgenet.msu.edu/swim/index.html, 21 October 2022) [28]. After imputation with PHARP v2, quality control (R2 > 0.8 and MAF > 0.05) was performed, and 9,093,720 SNPs were obtained. Additionally, the SNPs were further pruned by using the “--indep-pairwise 50 5 0.9” command with a sliding window of 50 SNPs, a 5-step SNP shift, and an r2 less than 0.9. Similarly, SNPs imputed using the SWIM online software were subjected to the relevant quality control procedure. Finally, with the online imputation software PHARP and SWIM, 1,017,199 and 1,019,225 autosomal SNPs were retained.

2.4. Estimation of Genetic Parameters and Genetic Correlation

The variance and covariance components and genetic correlations of the five traits were calculated using a repeatability model in DMU v6.0 software [29].
The animal model was as follows:
y = X b + Z a a + Z p e p e + e
In the model, y is a vector of phenotype records; b is the fixed effect of herd-year-season and parity with eight levels; X is a design matrix relating b to y; a is a vector of additive genetic effects; pe is a vector of random permanent environmental effects; and e is a vector of random residual effects. Za and Zpe are the corresponding incidence matrices.
The genetic correlation was calculated as follows:
r 12 = cov ( a 1 , a 2 ) σ a 1 σ a 2
where r 12 is the genetic correlation between trait 1 and trait 2, a 1 and a 2 represent the additive genetic values of trait 1 and trait 2 for the same individuals, and cov ( a 1 , a 2 ) , σ a 1 , and σ a 2 refer to the genetic covariance of two traits and the genetic standard deviations of trait 1 and trait 2, respectively.

2.5. Genome-Wide Association Study (GWAS)

To perform GWAS, we used the sum of an individual’s estimated breeding value (EBV) and residual as the adjusted phenotype in this study. We used fixed and random model circulating probability unification (FarmCPU) models for GWAS in GAPIT3 [30]. This method iteratively takes advantage of the mixed linear model (MLM) as the random model and stepwise regression as the fixed model [31]. In this study, we used the Bonferroni correction method to find candidate SNPs. p < 1/N represents the genome-wide suggestive significance threshold. p < 0.05/N represents the genome-wide significance threshold. Manhattan and Q-Q plots were generated using the R CMplot package version 4.2.0 [32].

2.6. Candidate Gene Search

We used BedTools [33] to search for candidate genes in the regions 0.5 Mb downstream and upstream of the significant SNPs based on the pig reference genome (http://useast.ensembl.org/Sus_scrofa/Info/Index/, accessed on 16 December 2022, Sscrofa11.1). Additionally, to better understand the biological processes and pathways of these candidate genes, we also performed enrichment analyses. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and Gene Ontology (GO) terms were enriched via KOBAS-i [34].

3. Results

3.1. Genetic Parameters and Genetic Correlations of Reproductive Traits

The genetic parameters of the five reproductive traits are presented in Table 2. The heritability estimates of TNB, NBA, LBW, GL, and NW were 0.0442 ± 0.0011, 0.0442 ± 0.0012, 0.0476 ± 0.0025, 0.1571 ± 0.0009, and 0.0727 ± 0.0021, respectively. As can be seen, these traits are all low-heritability traits. Table 3 shows the genetic correlations of the five reproductive traits. The genetic correlations ranged from −0.235 to 0.985, with standard errors ranging from 0.001 to 0.015. Among the five reproductive traits, TNB, NBA, LBW, and NW show strong positive correlations, with correlations ranging from 0.751 to 0.985. In contrast, GL shows some negative correlations with the remaining four traits, but the correlations are not strong.

3.2. Identification of Significant SNPs Associated with Reproductive Traits before Imputation

In GWAS based on chip data, only three SNPs on chromosome 13 for GL reach chromosome-level significance [p < 1.60 × 10−6 (0.05/33,175)] (Figure 1A). These SNPs are located in candidate genes such as DDPA4 and DDPA2 (Table 4). Additionally, there are 5, 6, 11, and 7 SNPs that exceed the suggestive significance threshold [p < 3.01 × 10−5 (1/33,175)] for TNB, LBW, NBA, and GL, respectively (Supplementary Table S2).

3.3. Identification of Significant SNPs Associated with Reproductive Traits after Imputation with PHARP

Figure 2A shows the results of Manhattan plots after imputation using PHARP. The Q-Q plots are shown in Figure 2B, with genome inflation factors between 0.964 and 1.095 (Supplementary Table S1). The results show that 22 and 3 genome-wide significant SNPs [p < 4.91 × 10−8 (0.05/1,017,199)] for TNB and GL are identified, respectively (Table 5). Notably, 14 genes are identified as related to reproduction, including MRTO4, TAS1R2, PAX7, CAPZB, UBR4, KCNJ2, MITF, LDHA, LDHC, ABCC8, ARGFX, and IGSF11. According to the suggestive significance threshold [p < 9.83 × 10−7 (1/1,017,199)], 8, 3, 1, and 186 SNPs are found to be associated with TNB, NBA, LBW, and GL, respectively (Supplementary Table S3).

3.4. Identification of Significant SNPs Associated with Reproductive Traits after Imputation with SWIM

Figure 3A shows the Manhattan plots of the genotype imputed using SWIM for GWAS. The Q-Q plots are shown in Figure 3B, with genome inflation factors between 0.889 and 1.132 (Supplementary Table S1). Overall, 271 SNPs reaching suggestive significance [p < 9.81 × 10−7 (1/1,019,225)] were found to be associated with the five reproductive traits (Supplementary Table S4). Further, 43 SNPs reach the genome-wide significance level: 8 SNPs for TNB, 3 SNPs for NBA, 8 SNPs for LBW, and 24 SNPs for GL. These significant SNPs were annotated to a number of candidate genes associated with reproduction, such as MYOCD, HMGN1, DACH1, GPC5, RPS6KA2, ARAP2, CAMK2A, and RGS18 (Table 6).

3.5. Bioinformatics Annotation Analysis

In this research, candidate functional genes were found by searching 0.5 Mb upstream and downstream of the suggestive SNPs using GWAS based on chip data and two imputed databases. The genes associated with TNB are found to be linked to glycolysis/gluconeogenesis, TGF-β, the oxytocin signaling pathway, and oocyte maturation processes. For NBA and LBW, the same genes, PDGFRB, CAMK2A, and MMP2, are identified, mainly enriched in the calcium signaling pathway, GnRH signaling pathway, and embryonic organ development process. Finally, the functional genes related to GL are enriched in the mTOR signaling pathway, ovarian steroidogenesis, prolactin signaling pathway, embryo development, and regulation of G protein-coupled receptor signaling pathway (Table 7).

4. Discussion

Reproductive traits such as TNB, NBA, LBW, GL, and NW are closely related to sow fertility and are important quantitative indicators of pig production. However, most of them have low heritability due to the complexity of the genetic structure. Therefore, it is important to clarify the genetic relationships between reproductive traits and to identify key candidate genes. In this study, a repeatability model was used to estimate the heritability of reproductive traits. The heritability estimates of the TNB, NBA, LBW, GL, and NW traits were 0.0442, 0.0442, 0.0476, 0.1571, and 0.0727, respectively. This is in agreement with the results of previous studies [35,36,37]. Additionally, we also calculated genetic correlations between individual traits and found strong positive correlations between TNB, NBA, LBW, and NW, with correlation coefficients ranging from 0.751 to 0.985, in agreement with previous reports [38,39]. This suggests that fewer traits can be selected to simplify breeding work.
Genotype imputation has been widely used in recent years with the development of sequencing technologies, price reductions, and the demand for high-density markers. This approach allows the imputation of chip data with low-density markers to WGS data, and the imputation accuracy is affected by the density of the target SNPs, the size of the reference population, the genetic distance between the target and imputation reference population, and the imputation procedure [40]. In our study, we imputed chip data using two publicly available online populating platforms. PHARP v2 provides genotype imputation using Minimac4, and the reference panel includes 4096 haplotypes, 53 million autosome SNPs, and 122 pig breeds [27]. The reference panel of SWIM 1.0 has a total of 2259 pigs, representing 44 different breeds. Based on the imputed data of the two imputation platforms mentioned above, combined with chip data, we performed GWAS for five reproductive traits.
In our study, we conducted GWAS for five reproductive traits using imputation data from two different online imputation platforms. Imputation data based on the SWIM platform detected more significant or potentially significant loci compared to the PHARP platform. This may be due to the fact that the SWIM platform has a larger number of pigs in its reference panel. In addition, an imputation strategy could improve on previous SNP-based studies without the need for additional data and expense. Furthermore, a common set of SNPs can be obtained with an imputation approach, thus making a meta-analysis possible.
Some studies have shown that the FarmCPU model can be effective in GWASs for identifying loci with low-heritability traits [35]. So, we performed GWAS by using the FarmCPU model, which divides the MLM into two parts and uses them iteratively [31]. For the TNB trait, a total of 19 suggestive candidate genes were identified based on chip data and imputed data. Among them, the RPS6KA2 gene plays a major role in the EGF signaling cascade at ovulation, which is also correlated with oocyte developmental quality [41]. As a transcription factor, SMAD4 plays an important role in the porcine reproductive system. It has been shown that miR-143 [42], miR-26b [43], and miR-10b [44] can inhibit apoptosis and promote E2 release via SMAD4 in porcine granulosa cells. For both the NBA and LBW traits, GWAS based on imputed data identified the CAMK2A, NDST1, and RPS14 genes. In a meta-analysis of reproductive traits in heifers, the CAMK2A gene was identified as being involved in calcium signaling mechanisms and acting on pituitary gonadotropin secretion [45]. This is consistent with our findings. In addition, NDST1 has been shown to be critical for many organogenesis processes, and the targeted disruption of the NDST1 gene impaired heart development in mice [46]. NSDT1 f/f/2 null/3 null mice with defective decidualization resulted in female infertility [47]. It has been reported that RSP14 is a key gene in early embryonic development [48]. Embryonic stem cells heterozygous for the RSP14 gene showed defects in embryoid body differentiation [49]. For the GL trait, both GWASs based on chip data and imputed data identified genome-wide significant SNPs. Based on KEGG and GO analyses, we annotated a total of 13 candidate genes, mainly related to the ovarian steroidogenesis pathway and embryo development process. Among these, ADCY5 was identified as being associated with seasonal estrus in Sunite sheep [50], egg production in white Muscovy ducks [51], and fertility in cows [52], while in human GWAS, ADCY5 was found to be associated with gestational duration [53]. Interestingly, it has been reported that ADCY5 is associated with fetal growth and birth weight [54]. However, the ADCY5 gene has not been studied in pig reproduction, and we speculate that this gene may be a key gene in the influence of reproductive performance in pigs. Unfortunately, no potential SNPs were identified for the NW trait, probably due to the small size of the population and the high number of missing phenotypic data points. Overall, our results identify a number of new key candidate genes and loci associated with reproductive traits in large white pigs, but further studies are needed to confirm the functions of these genes.

5. Conclusions

In this study, the genetic parameters of TNB, NBA, LBW, GL, and NW in Yorkshire pigs were estimated using a repeatability model. These traits are low-heritability traits. There were strong positive correlations between TNB, NBA, LBW, and NW, excluding the GL trait, which was weakly negatively correlated with them. GWASs based on chip data and imputed data were performed for five reproductive traits in Yorkshire pigs. Finally, combining the results of GWAS and bioinformatics annotation analysis, SMAD4, RPS6KA2, CAMK2A, NDST1, and ADCY5 were identified as novel genes, and some of them have not been studied in livestock, so they may be key candidate genes affecting reproductive traits in pigs. The results of this study highlight some new major genes regulating reproductive traits in pigs and can benefit genome selection for pig genetic breeding.

Supplementary Materials

The following supporting information can be downloaded at https://www.mdpi.com/article/10.3390/genes14040861/s1, Table S1. The genomic inflation factor (λ) for each GWAS using chip and imputation data of pigs. Table S2. Genes within 0.5 Mb of suggestive significant SNPs identified by GWAS based on chip data for reproductive traits. Table S3. Genes within 0.5 Mb of suggestive significant SNPs identified by GWAS based on the PHARP imputation data for reproductive traits. Table S4. Genes within 0.5 Mb of suggestive significant SNPs identified by GWAS based on SWIM imputation data for reproductive traits.

Author Contributions

G.Y. and X.D. conceived and supervised the study. Y.J., M.C., and J.W. helped complete the imputation of the chip data. T.Y. provided technical guidance. J.X. collected the samples and recorded the phenotypes. Y.W. extracted the DNA for genotyping. J.S. analyzed the data and wrote the manuscript. All authors have read and agreed to the published version of the manuscript.

Funding

The authors are grateful to all the funding agencies. This work was supported by the National Key R&D Program of China (2021YFF1000602, 2021YFD1301200) and China Agriculture Research System (CARS-35-PIG).

Institutional Review Board Statement

The whole collection procedure of ear tissue samples was approved by the Institutional Animal Care and Use Committee of the Northwest A & F University (approval number: NWAFU-314021167).

Informed Consent Statement

Not applicable.

Data Availability Statement

Data are available from the corresponding author on reasonable request.

Conflicts of Interest

The authors declare that they have no competing interests.

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Figure 1. Manhattan and Q-Q plots of GWAS based on chip data for five reproductive traits. (A). The red line represents the genome-wide significance level. The blue line represents the suggestive significance (3.01 × 10−5). Red spots identify SNPs with genome-wide significance (1.60 × 10−6). Traits from the inner to outer lanes are gestation length (GL), litter birth weight (LBW), number born alive (NBA), number of weaned (NW), and total number born (TNB). (B). Q-Q plots of five reproductive traits.
Figure 1. Manhattan and Q-Q plots of GWAS based on chip data for five reproductive traits. (A). The red line represents the genome-wide significance level. The blue line represents the suggestive significance (3.01 × 10−5). Red spots identify SNPs with genome-wide significance (1.60 × 10−6). Traits from the inner to outer lanes are gestation length (GL), litter birth weight (LBW), number born alive (NBA), number of weaned (NW), and total number born (TNB). (B). Q-Q plots of five reproductive traits.
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Figure 2. Manhattan and Q-Q plots of GWAS based on data imputation using PHARP for five reproductive traits. (A) The red line represents the genome-wide significance level (4.91 × 10−8). The blue line represents the suggestive significance (9.83 × 10−7). (B) Q-Q plots of five reproductive traits. Abbreviations: GL = gestation length, LBW = litter birth weight, NBA = number born alive, NW = number of weaned, TNB = total number born.
Figure 2. Manhattan and Q-Q plots of GWAS based on data imputation using PHARP for five reproductive traits. (A) The red line represents the genome-wide significance level (4.91 × 10−8). The blue line represents the suggestive significance (9.83 × 10−7). (B) Q-Q plots of five reproductive traits. Abbreviations: GL = gestation length, LBW = litter birth weight, NBA = number born alive, NW = number of weaned, TNB = total number born.
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Figure 3. Manhattan and Q-Q plots of GWAS based on data imputation with SWIM for five reproductive traits. (A) The red line represents the genome-wide significance level (4.90 × 10−8). The blue line represents the suggestive significance (9.81 × 10−7). (B) Q-Q plots of five reproductive traits. Abbreviations: GL = gestation length, LBW = litter birth weight, NBA = number born alive, NW = number of weaned, TNB = total number born.
Figure 3. Manhattan and Q-Q plots of GWAS based on data imputation with SWIM for five reproductive traits. (A) The red line represents the genome-wide significance level (4.90 × 10−8). The blue line represents the suggestive significance (9.81 × 10−7). (B) Q-Q plots of five reproductive traits. Abbreviations: GL = gestation length, LBW = litter birth weight, NBA = number born alive, NW = number of weaned, TNB = total number born.
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Table 1. Descriptive statistics for five reproductive traits.
Table 1. Descriptive statistics for five reproductive traits.
Traits 1N-obs 2MeanS.D.CV 3 (%)Min ValueMax Value
TNB10,0889.932.5425.6318
NBA98629.252.5327.2317
LBW989712.473.7229.82.430
GL10,193114.651.491.3105127
NW58578.752.4628.1217
1 TNB: total number born; NBA: number born alive; LBW: litter birth weight; GL: gestation length; NW: number of weaned. 2 N-obs: number of observations. 3 CV: coefficient of variation.
Table 2. Estimates of variance components and genetic parameters for five reproductive traits.
Table 2. Estimates of variance components and genetic parameters for five reproductive traits.
Traits 1 σ a 2  2 σ p e 2  3 σ e 2  4h2SE
TNB0.26870.52895.28030.04420.0011
NBA0.27000.55315.28560.04420.0012
LBW0.60081.110410.90990.04760.0025
GL0.33130.17651.60080.15710.0009
NW0.40520.17444.99220.07270.0021
1 TNB: total number born; NBA: number born alive; LBW: litter birth weight; GL: gestation length; NW: number of weaned. 2   σ a 2 : additive genetic variance. 3  σ p e 2 : permanent environmental effect variance. 4  σ e 2 : residual effect variance.
Table 3. Genetic correlations between five reproductive traits.
Table 3. Genetic correlations between five reproductive traits.
Traits 1TNBNBALBWGLNW
TNB 0.985 (0.001)0.886 (0.003)−0.235 (0.010)0.751 (0.005)
NBA 0.945 (0.001)−0.188 (0.010)0.850 (0.003)
LBW −0.120 (0.015)0.934 (0.002)
GL −0.176 (0.011)
NW
1 TNB: total number born; NBA: number born alive; LBW: litter birth weight; GL: gestation length; NW: number of weaned. SEs of estimates are in parentheses.
Table 4. The significant SNPs in the genome for the gestation length (GL) trait using chip data in pigs.
Table 4. The significant SNPs in the genome for the gestation length (GL) trait using chip data in pigs.
Traits 1 SNP 2 Chr 3 Position p -Value Candidate Gene
GL 13:150210534131502105342.13 × 10−7 DPPA4 , DPPA2
13:156135228131561352282.24 × 10−7
13:156180521131561805216.75 × 10−7
1 GL: gestation length; 2 SNP: single-nucleotide polymorphism; 3 Chr: chromosome.
Table 5. The significant SNPs in the genome with the total number born (TNB) and gestation length (GL) traits using data imputed with PHARP.
Table 5. The significant SNPs in the genome with the total number born (TNB) and gestation length (GL) traits using data imputed with PHARP.
Traits 1SNP 2Chr 3Positionp-ValueCandidate Genes
TNB6:775016246775016246.07 × 10−36MRTO4, TAS1R2, PAX7, CAPZB, UBR4
6:772969866772969861.36 × 10−27MRTO4, TAS1R2, PAX7, CAPZB, UBR4
12:1003295512100329551.16 × 10−12KCNJ2
13:5185284913518528497.91 × 10−7MITF
6:773251666773251661.30 × 10−11MRTO4, TAS1R2, PAX7, CAPZB, UBR4
6:773304646773304641.30 × 10−11MRTO4, TAS1R2, PAX7, CAPZB, UBR4
6:774580516774580511.30 × 10−11MRTO4, TAS1R2, PAX7, CAPZB, UBR4
6:774628536774628531.30 × 10−11MRTO4, TAS1R2, PAX7, CAPZB, UBR4
6:774809786774809781.30 × 10−11MRTO4, TAS1R2, PAX7, CAPZB, UBR4
9:10558209891055820982.14 × 10−11-
6:773523076773523078.67 × 10−11MRTO4, TAS1R2, PAX7, CAPZB, UBR4
6:773545146773545148.67 × 10−11MRTO4, TAS1R2, PAX7, CAPZB, UBR4
6:773642376773642378.67 × 10−11MRTO4, TAS1R2, PAX7, CAPZB, UBR4
6:774733206774733208.67 × 10−11MRTO4, TAS1R2, PAX7, CAPZB, UBR4
6:773352506773352504.47 × 10−10MRTO4, TAS1R2, PAX7, CAPZB, UBR4
6:773423856773423859.30 × 10−10MRTO4, TAS1R2, PAX7, CAPZB, UBR4
6:775001106775001109.30 × 10−10MRTO4, TAS1R2, PAX7, CAPZB, UBR4
6:775067946775067949.30 × 10−10MRTO4, TAS1R2, PAX7, CAPZB, UBR4
6:775513996775513999.30 × 10−10MRTO4, TAS1R2, PAX7, CAPZB, UBR4
6:774012186774012189.30 × 10−10MRTO4, TAS1R2, PAX7, CAPZB, UBR4
2:412347402412347401.89 × 10−8LDHA, LDHC, ABCC8
10:6710150910671015093.72 × 10−8PFKP
GL13:139111128131391111281.25 × 10−8ARGFX
13:141726529131417265291.96 × 10−8IGSF11
13:141659895131416598953.47 × 10−8IGSF11
1 TNB: total number born; GL: gestation length; 2 SNP: single-nucleotide polymorphism; 3 Chr: chromosome.
Table 6. The significant SNPs in the genome for the total number born (TNB) and gestation length (GL) traits using data imputed with SWIM.
Table 6. The significant SNPs in the genome for the total number born (TNB) and gestation length (GL) traits using data imputed with SWIM.
Traits 1SNP 2Chr 3Positionp-ValueCandidate Gene
TNB12:5683913412568391343.94 × 10−20MYOCD
12:5684092812568409283.09 × 10−19MYOCD
13:202985373132029853732..91 × 10−12HMGN1
11:4336798111433679812.78 × 10−10DACH1
11:6030085111603008513.06 × 10−9GPC5
10:39136251039136253.82 × 10−9-
1:2245988122459881.61 × 10−8RPS6KA2
11:6022696311602269632.43 × 10−8-
NBA8:273775468273775463.44 × 10−8ARAP2
2:15152514221515251424.56 × 10−8RPS14, NDST1, CAMK2A
2:15161630221516163024.56 × 10−8CAMK2A, SYNPO, NDST1
LBW2:15152514221515251429.82 × 10−17RPS14, NDST1, CAMK2A
2:15163573421516357341.01 × 10−14RPS14, NDST1, CAMK2A
3:145598783145598784.05 × 10−10AUTS2
3:2296285322962853.29 × 10−9CARD11
6:302066256302066254.60 × 10−9IRX6
8:273775468273775462.24 × 10−8ARAP2
17:1303453517130345352.64 × 10−8PSD3
GL10:17966971017966971.12 × 10−8RGS18
10:18056791018056791.12 × 10−8RGS18
10:18098381018098381.12 × 10−8RGS18
10:18205241018205241.12 × 10−8RGS18
10:18384061018384061.12 × 10−8RGS18
10:18471061018471061.12 × 10−8RGS18
10:18558461018558461.12 × 10−8RGS18
10:17840121017840121.12 × 10−8RGS18
10: 18013161018013161.12 × 10−8RGS18
10:18169381018169381.12 × 10−8RGS18
10:18240281018240281.12 × 10−8RGS18
10:18530981018530981.12 × 10−8RGS18
10:18987841018987841.12 × 10−8RGS18
10:19778191019778191.12 × 10−8RGS18
10:19901601019901601.12 × 10−8RGS18
10:20002111020002111.12 × 10−8RGS18
10:17118121017118121.68 × 10−8RGS18
10:16998921016998921.96 × 10−8RGS18
10:15168751015168752.38 × 10−8RGS18
10:17196671017196672.63 × 10−8RGS18
10:17226981017226982.63 × 10−8RGS18
10:15495451015495453.75 × 10−8RGS18
10:17689051017689054.79 × 10−8RGS18
10:17720641017720644.79 × 10−8RGS18
1 TNB: total number born; GL: gestation length; 2 SNP: single-nucleotide polymorphism; 3 Chr: chromosome.
Table 7. Significant KEGG pathways and GO terms associated with productive traits in pigs (p < 0.05).
Table 7. Significant KEGG pathways and GO terms associated with productive traits in pigs (p < 0.05).
Traits 1TermDatabase 2IDGene Names
TNBGlycolysis/gluconeogenesisKEGG PATHWAYssc00010LDHC|LDHA|PFKP
TGF-β signaling pathwayKEGG PATHWAYssc04350SMAD4|NBL1
Oxytocin signaling pathwayKEGG PATHWAYssc04921KCNJ2|RYR2
uterus developmentGene OntologyGO:0060065SMAD4
oocyte maturationGene OntologyGO:0001556RPS6KA2
NBACalcium signaling pathwayKEGG PATHWAYssc04020PDGFRB|ADRA1B|CAMK2A
GnRH signaling pathwayKEGG PATHWAYssc04912MMP2|CAMK2A
Embryonic organ developmentGene OntologyGO:0048568PDGFRB
LBWMAPK signaling pathwayKEGG PATHWAYssc04010PDGFRB|GNA12|CSF1R
PPAR signaling pathwayKEGG PATHWAYssc03320FABP4|FABP5
Regulation of actin cytoskeletonKEGG PATHWAYssc04810PDGFRB|GNA12
In utero embryonic developmentGene OntologyGO:0001701PDGFRB|GNA12
Hormone receptor bindingGene OntologyGO:0051427FABP4
cell developmentGene OntologyGO:0048468IRX5|IRX6
GLmTOR signaling pathwayKEGG PATHWAYssc04150ATP6V1C2|ATP6V1A|GSK3B
Ovarian steroidogenesisKEGG PATHWAYssc04913ADCY5
Prolactin signaling pathwayKEGG PATHWAYssc04917GSK3B
Embryo developmentGene OntologyGO:0009790DLX4|DLX3
Regulation of G protein-coupled receptor signaling pathwayGene OntologyGO:0008277RGS18
1 TNB: total number born; NBA: number born alive; LBW: litter birth weight; GL: gestation length; NW: number of weaned. 2 KEGG: Kyoto Encyclopedia of Genes and Genomes.
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Sun, J.; Xiao, J.; Jiang, Y.; Wang, Y.; Cao, M.; Wei, J.; Yu, T.; Ding, X.; Yang, G. Genome-Wide Association Study on Reproductive Traits Using Imputation-Based Whole-Genome Sequence Data in Yorkshire Pigs. Genes 2023, 14, 861. https://doi.org/10.3390/genes14040861

AMA Style

Sun J, Xiao J, Jiang Y, Wang Y, Cao M, Wei J, Yu T, Ding X, Yang G. Genome-Wide Association Study on Reproductive Traits Using Imputation-Based Whole-Genome Sequence Data in Yorkshire Pigs. Genes. 2023; 14(4):861. https://doi.org/10.3390/genes14040861

Chicago/Turabian Style

Sun, Jingchun, Jinhong Xiao, Yifan Jiang, Yaxin Wang, Minghao Cao, Jialin Wei, Taiyong Yu, Xiangdong Ding, and Gongshe Yang. 2023. "Genome-Wide Association Study on Reproductive Traits Using Imputation-Based Whole-Genome Sequence Data in Yorkshire Pigs" Genes 14, no. 4: 861. https://doi.org/10.3390/genes14040861

APA Style

Sun, J., Xiao, J., Jiang, Y., Wang, Y., Cao, M., Wei, J., Yu, T., Ding, X., & Yang, G. (2023). Genome-Wide Association Study on Reproductive Traits Using Imputation-Based Whole-Genome Sequence Data in Yorkshire Pigs. Genes, 14(4), 861. https://doi.org/10.3390/genes14040861

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