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In general, the relationship between the predicted functional consequences of missense mutations mapping to genes known to be involved in human diseases and the severity of disease manifestations is weak. In this study, we tested in pigs whether missense single nucleotide polymorphisms (SNPs), predicted to have consequences on the function of genes related to lipid metabolism are associated with lipid phenotypes. Association analysis demonstrated that nine out of 72 nominally associated SNPs were classified as "highly" or "very highly consistent" in silico-predicted functional mutations and did not show association with lipid traits expected to be affected by inactivation of the corresponding gene. Although the lack of endophenotypes and the limited sample size of certain genotypic classes might have limited to some extent the reach of the current study, our data indicate that present-day bioinformatic tools have a modest ability to predict the impact of missense mutations on complex phenotypes.

This is the first study to explore the genetic diversity and population structure of domestic water buffalo (Bubalus bubalis) in Germany and their potential relations to herds in other parts of Europe or worldwide. To this end, animals from different herds in Germany, Bulgaria, Romania, and Hungary were genotyped and compared to genotypes from other populations with worldwide distribution and open to the public. The pilot study analyzed population structure, phylogenetic tree, and inbreeding events in our samples. In buffalos from Germany, a mixed genetic make-up with contributions from Bulgaria (Murrah breed), Romania, and Italy was found. All in all, a high degree of genetic diversity was identified in European buffalos, and a novel genotype was described in Hungarian buffalos by this study. We demonstrate that European buffalos stand out from other buffalo populations worldwide, supporting the idea that buffalos have not completely disappeared from the European continent during the late Pleistocene. The high genetic diversity in European buffalos seems to be an excellent prerequisite for the establishment of local breeds characterized by unique traits and features. This study may also be considered as an initial step on the way to genome characterization for the sustainable development of the buffalo economy in Germany and other parts of Europe in the future.

[Background]: The role of non-coding RNAs in the porcine muscle metabolism is poorly understood, with few studies investigating their expression patterns in response to nutrient supply. Therefore, we aimed to investigate the changes in microRNAs (miRNAs), long intergenic non-coding RNAs (lincRNAs) and mRNAs muscle expression before and after food intake., [Results]: We measured the miRNA, lincRNA and mRNA expression levels in the gluteus medius muscle of 12 gilts in a fasting condition (AL-T0) and 24 gilts fed ad libitum during either 5 h. (AL-T1, N = 12) or 7 h. (AL-T2, N = 12) prior to slaughter. The small RNA fraction was extracted from muscle samples retrieved from the 36 gilts and sequenced, whereas lincRNA and mRNA expression data were already available. In terms of mean and variance, the expression profiles of miRNAs and lincRNAs in the porcine muscle were quite different than those of mRNAs. Food intake induced the differential expression of 149 (AL-T0/AL-T1) and 435 (AL-T0/AL-T2) mRNAs, 6 (AL-T0/AL-T1) and 28 (AL-T0/AL-T2) miRNAs and none lincRNAs, while the number of differentially dispersed genes was much lower. Among the set of differentially expressed miRNAs, we identified ssc-miR-148a-3p, ssc-miR-22-3p and ssc-miR-1, which play key roles in the regulation of glucose and lipid metabolism. Besides, co-expression network analyses revealed several miRNAs that putatively interact with mRNAs playing key metabolic roles and that also showed differential expression before and after feeding. One case example was represented by seven miRNAs (ssc-miR-148a-3p, ssc-miR-151-3p, ssc-miR-30a-3p, ssc-miR-30e-3p, ssc-miR-421-5p, ssc-miR-493-5p and ssc-miR-503) which putatively interact with the PDK4 mRNA, one of the master regulators of glucose utilization and fatty acid oxidation., [Conclusions]: As a whole, our results evidence that microRNAs are likely to play an important role in the porcine skeletal muscle metabolic adaptation to nutrient availability.

[Background]: Genetic pressure in animal breeding is sparking the interest of breeders for selecting elite boars with higher sperm quality to optimize ejaculate doses and fertility rates. However, the molecular basis of sperm quality is not yet fully understood. Our aim was to identify candidate genes, pathways and DNA variants associated to sperm quality in swine by analysing 25 sperm-related phenotypes and integrating genome-wide association studies (GWAS) and RNA-seq under a systems biology framework., [Results]: By GWAS, we identified 12 quantitative trait loci (QTL) associated to the percentage of head and neck abnormalities, abnormal acrosomes and motile spermatozoa. Candidate genes included CHD2, KATNAL2, SLC14A2 and ABCA1. By RNA-seq, we identified a wide repertoire of mRNAs (e.g. PRM1, OAZ3, DNAJB8, TPPP2 and TNP1) and miRNAs (e.g. ssc-miR-30d, ssc-miR-34c, ssc-miR-30c-5p, ssc-miR-191, members of the let-7 family and ssc-miR-425-5p) with functions related to sperm biology. We detected 6128 significant correlations (P-value ≤ 0.05) between sperm traits and mRNA abundances. By expression (e)GWAS, we identified three trans-expression QTL involving the genes IQCJ, ACTR2 and HARS. Using the GWAS and RNA-seq data, we built a gene interaction network. We considered that the genes and interactions that were present in both the GWAS and RNA-seq networks had a higher probability of being actually involved in sperm quality and used them to build a robust gene interaction network. In addition, in the final network we included genes with RNA abundances correlated with more than four semen traits and miRNAs interacting with the genes on the network. The final network was enriched for genes involved in gamete generation and development, meiotic cell cycle, DNA repair or embryo implantation. Finally, we designed a panel of 73 SNPs based on the GWAS, eGWAS and final network data, that explains between 5% (for sperm cell concentration) and 36% (for percentage of neck abnormalities) of the phenotypic variance of the sperm traits., [Conclusions]: By applying a systems biology approach, we identified genes that potentially affect sperm quality and constructed a SNP panel that explains a substantial part of the phenotypic variance for semen quality in our study and that should be tested in other swine populations to evaluate its relevance for the pig breeding sector.

[Background]: Feed efficiency (FE) has a major impact on the economic sustainability of pig production. We used a systems-based approach that integrates single nucleotide polymorphism (SNP) co-association and gene-expression data to identify candidate genes, biological pathways, and potential predictors of FE in a Duroc pig population., [Results]: We applied an association weight matrix (AWM) approach to analyse the results from genome-wide association studies (GWAS) for nine FE associated and production traits using 31K SNPs by defining residual feed intake (RFI) as the target phenotype. The resulting co-association network was formed by 829 SNPs. Additive effects of this SNP panel explained 61% of the phenotypic variance of RFI, and the resulting phenotype prediction accuracy estimated by cross-validation was 0.65 (vs. 0.20 using pedigree-based best linear unbiased prediction and 0.12 using the 31K SNPs). Sixty-eight transcription factor (TF) genes were identified in the co-association network; based on the lossless approach, the putative main regulators were COPS5, GTF2H5, RUNX1, HDAC4, ESR1, USP16, SMARCA2 and GTF2F2. Furthermore, gene expression data of the gluteus medius muscle was explored through differential expression and multivariate analyses. A list of candidate genes showing functional and/or structural associations with FE was elaborated based on results from both AWM and gene expression analyses, and included the aforementioned TF genes and other ones that have key roles in metabolism, e.g. ESRRG, RXRG, PPARGC1A, TCF7L2, LHX4, MAML2, NFATC3, NFKBIZ, TCEA1, CDCA7L, LZTFL1 or CBFB. The most enriched biological pathways in this list were associated with behaviour, immunity, nervous system, and neurotransmitters, including melatonin, glutamate receptor, and gustation pathways. Finally, an expression GWAS allowed identifying 269 SNPs associated with the candidate genes’ expression (eSNPs). Addition of these eSNPs to the AWM panel of 829 SNPs did not improve the accuracy of genomic predictions., [Conclusions]: Candidate genes that have a direct or indirect effect on FE-related traits belong to various biological processes that are mainly related to immunity, behaviour, energy metabolism, and the nervous system. The pituitary gland, hypothalamus and thyroid axis, and estrogen signalling play fundamental roles in the regulation of FE in pigs. The 829 selected SNPs explained 61% of the phenotypic variance of RFI, which constitutes a promising perspective for applying genetic selection on FE relying on molecular-based prediction.

[Background]: The comparison of expression QTL (eQTL) maps obtained in different tissues is an essential step to understand how gene expression is genetically regulated in a context-dependent manner. In the current work, we have compared the transcriptomic and eQTL profiles of two porcine tissues (skeletal muscle and liver) which typically show highly divergent expression profiles, in 103 Duroc pigs genotyped with the Porcine SNP60 BeadChip (Illumina) and with available microarray-based measurements of hepatic and muscle mRNA levels. Since structural variation could have effects on gene expression, we have also investigated the co-localization of cis-eQTLs with copy number variant regions (CNVR) segregating in this Duroc population., [Results]: The analysis of differential expresssion revealed the existence of 1204 and 1490 probes that were overexpressed and underexpressed in the gluteus medius muscle when compared to liver, respectively (|fold-change| > 1.5, q-value < 0.05). By performing genome scans in 103 Duroc pigs with available expression and genotypic data, we identified 76 and 28 genome-wide significant cis-eQTLs regulating gene expression in the gluteus medius muscle and liver, respectively. Twelve of these cis-eQTLs were shared by both tissues (i.e. 42.8% of the cis-eQTLs identified in the liver were replicated in the gluteus medius muscle). These results are consistent with previous studies performed in humans, where 50% of eQTLs were shared across tissues. Moreover, we have identified 41 CNVRs in a set of 350 pigs from the same Duroc population, which had been genotyped with the Porcine SNP60 BeadChip by using the PennCNV and GADA softwares, but only a small proportion of these CNVRs co-localized with the cis-eQTL signals., [Conclusion]: Despite the fact that there are considerable differences in the gene expression patterns of the porcine liver and skeletal muscle, we have identified a substantial proportion of common cis-eQTLs regulating gene expression in both tissues. Several of these cis-eQTLs influence the mRNA levels of genes with important roles in meat (CTSF) and carcass quality (TAPT1), lipid metabolism (TMEM97) and obesity (MARC2), thus evidencing the practical importance of dissecting the genetic mechanisms involved in their expression.

[Background]: Intramuscular fat (IMF) content and composition have a strong impact on the nutritional and organoleptic properties of porcine meat. The goal of the current work was to compare the patterns of gene expression and the genetic determinism of IMF traits in the porcine gluteus medius (GM) and longissimus dorsi (LD) muscles., [Results]: A comparative analysis of the mRNA expression profiles of the pig GM and LD muscles in 16 Duroc pigs with available microarray mRNA expression measurements revealed the existence of 106 differentially expressed probes (fold-change > 1.5 and q-value < 0.05). Amongst the genes displaying the most significant differential expression, several loci belonging to the Hox transcription factor family were either upregulated (HOXA9, HOXA10, HOXB6, HOXB7 and TBX1) or downregulated (ARX) in the GM muscle. Differences in the expression of genes with key roles in carbohydrate and lipid metabolism (e.g. FABP3, ORMDL1 and SLC37A1) were also detected. By performing a GWAS for IMF content and composition traits recorded in the LD and GM muscles of 350 Duroc pigs, we identified the existence of one region on SSC14 (110–114 Mb) displaying significant associations with C18:0, C18:1(n-7), saturated and unsaturated fatty acid contents in both GM and LD muscles. Moreover, we detected several genome-wide significant associations that were not consistently found in both muscles. Further studies should be performed to confirm whether these associations are muscle-specific. Finally, the performance of an eQTL scan for 74 genes, located within GM QTL regions and with available microarray measurements of gene expression, made possible to identify 14 cis-eQTL regulating the expression of 14 loci, and six of them were confirmed by RNA-Seq., [Conclusions]: We have detected significant differences in the mRNA expression patterns of the porcine LD and GM muscles, evidencing that the transcriptomic profile of the skeletal muscle tissue is affected by anatomical, metabolic and functional factors. A highly significant association with IMF composition on SSC14 was replicated in both muscles, highlighting the existence of a common genetic determinism, but we also observed the existence of a few associations whose magnitude and significance varied between LD and GM muscles.

[Background]: The molecular basis of compensatory growth in monogastric animals has not yet been fully explored. Herewith, in this study we aim to determine changes in the pig skeletal muscle transcriptome profile during compensatory growth following a feed restriction period. A RNA-Seq experiment was performed with a total of 24 females belonging to a Duroc commercial line. Half of the animals received either a restricted (RE) or ad libitum (AL) diet during the first fattening period (60–125 d of age). After that, all gilts were fed ad libitum for a further ~30 d until the age of ~155 d, when animals were slaughtered and samples of gluteus medius muscle were harvested to perform RNA-Seq analyses and intramuscular fat content determination., [Results]: During the period following food restriction, RE animals re-fed ad libitum displayed compensatory growth, showed better feed conversion rate and tended to deposit more subcutaneous fat than AL fed animals. Animals were slaughtered in the phase of accelerated growth, when RE animals had not completely compensated the performance of AL group, showing lower live and carcass weights. At intramuscular level, RE gilts showed a higher content of polyunsaturated fatty acids during the compensatory growth phase. The comparison of RE and AL expression profiles allowed the identification of 86 (ǀlog2Fold-Changeǀ > 1, padj < 0.05) differentially expressed (DE) genes. A functional categorization of these DE genes identified AMPK Signaling as the most significantly enriched canonical pathway. This kinase plays a key role in the maintenance of energy homeostasis as well as in the activation of autophagy. Among the DE genes identified as components of AMPK Signaling pathway, five out of six genes were downregulated in RE pigs., [Conclusions]: Animals re-fed after a restriction period exhibited a less oxidative metabolic profile and catabolic processes in muscle than animals fed ad libitum. The downregulation of autophagy observed in the skeletal muscle of pigs undergoing compensatory growth may constitute a mechanism to increase muscle mass thus ensuring an accelerated growth rate. These results reveal that the downregulation of AMPK Signaling plays an important role in compensatory growth in pigs.

[Background]: The identification of genes differentially expressed in the skeletal muscle of pigs displaying distinct growth and fatness profiles might contribute to identify the genetic factors that influence the phenotypic variation of such traits. So far, the majority of porcine transcriptomic studies have investigated differences in gene expression at a global scale rather than at the mRNA isoform level. In the current work, we have investigated the differential expression of mRNA isoforms in the gluteus medius (GM) muscle of 52 Duroc HIGH (increased backfat thickness, intramuscular fat and saturated and monounsaturated fatty acids contents) and LOW pigs (opposite phenotype, with an increased polyunsaturated fatty acids content)., [Results]: Our analysis revealed that 10.9% of genes expressed in the GM muscle generate alternative mRNA isoforms, with an average of 2.9 transcripts per gene. By using two different pipelines, one based on the CLC Genomics Workbench and another one on the STAR, RSEM and DESeq2 softwares, we have identified 10 mRNA isoforms that both pipelines categorize as differentially expressed in HIGH vs LOW pigs (P-value < 0.01 and ±0.6 log2fold-change). Only five mRNA isoforms, produced by the ITGA5, SEMA4D, LITAF, TIMP1 and ANXA2 genes, remain significant after correction for multiple testing (q-value < 0.05 and ±0.6 log2fold-change), being upregulated in HIGH pigs., [Conclusions]: The increased levels of specific ITGA5, LITAF, TIMP1 and ANXA2 mRNA isoforms in HIGH pigs is consistent with reports indicating that the overexpression of these four genes is associated with obesity and metabolic disorders in humans. A broader knowledge about the functional attributes of these mRNA variants would be fundamental to elucidate the consequences of transcript diversity on the determinism of porcine phenotypes of economic interest.

Departament responsable de la tesi: Departament de Ciència Animal i dels Aliments, A la portada: Centre de Recerca en Agrigenòmica, El principal objetivo de la presente tesis fue identificar regiones genómicas asociadas con la variación fenotípica de caracteres relacionados con la calidad de la carne. Para ello se realizaron estudios de asociación genómica (GWAS) para el contenido y la composición de la grasa intramuscular así como para la conductividad eléctrica, el pH, y el color de la carne. Dichos fenotipos se midieron en los músculos gluteus medius (GM) y longissimus dorsi (LD) de cerdos pertenecientes a una línea comercial Duroc. En general, los SNPs incluidos en el PorcineSNP60 BeadChip de Illumina explicaron un porcentaje bajo o moderado (0-51%) de la varianza fenotípica de los caracteres evaluados en nuestra población. Mediante la aproximación GWAS, se identificaron un total de 40 QTLs significativos a nivel genómico y 101 QTLs significativos a nivel cromosómico. Se observó que la mayoría de los QTLs detectados fueron específicos de cada músculo y esto probablemente se deba a que los perfiles de expresión génica de ambos músculos son diferentes. Se detectaron además, varios QTLs con efecto en más de un fenotipo, lo que sugiere la existencia de regiones con efectos pleiotrópicos. Es importante destacar el QTL localizado en el cromosoma porcino SSC14, que presentó asociaciones significativas con el ácido esteárico, linoleico y los porcentajes de ácidos grasos saturados e insaturados en los dos músculos LD y GM. Además, se investigó si las regiones QTL para la calidad de la carne contienen QTL con efectos sobre la expresión génica (eQTL). Con este enfoque se detectaron cinco eQTLs cuyas posiciones coincidieron con QTLs para el pH, la conductividad eléctrica y el color de la carne. Por otra parte, también se identificaron 20 cis-eQTL y 116 trans-eQTL que mostraban concordancia posicional con QTLs para el contenido y la composición de la grasa intramuscular. De forma independiente, se analizó la regulación de la expresión génica de 63 loci cuyas funciones están relacionadas con el metabolism, The main objective of this thesis was to identify genomic regions associated with technological and lipid composition meat quality traits. In this way, we carried out a GWAS for 57 phenotypes measured in the gluteus medius (GM) and longissimus dorsi (LD) muscles of pigs from a commercial Duroc line. In general, SNPs included in the PorcineSNP60 BeadChip only explained a limited amount of the phenotypic variance of the meat quality traits recorded in our population (0-51%). Moreover, we detected 40 and 101 genome- and chromosome-wide significant associations respectively. The majority of these associations were muscle-specific, maybe because the GM and LD muscles have different profiles of mRNA expression. Several of these regions were associated with more than one trait, suggesting the existence of pleiotropic effects. Specifically relevant was the genomic region located on SSC14 (120-124 Mb) which was associated with stearic, linoleic, unsaturated, and saturated fatty acids in both LD and GM muscles. We also investigated if QTL regions contain expression QTL (eQTL) influencing the mRNA levels of loci transcribed in the GM muscle. The number of eQTL co-localizing with QTL for meat technological traits (5 cis-eQTLs) was lower than that of QTL for intramuscular fat (IMF) composition traits (20 cis-eQTL). Besides, we detected SNPs mapping to IMF QTL with trans-regulatory effects on gene expression (116 trans-eQTL). We were also interested in analysing the genetic regulation of lipid genes. With this goal, we have performed an eQTL scan for 63 loci that are known to have a key role in lipid metabolism. Our results revealed 13 cis- and 18 trans-eQTL modulating the expression of 19 loci with a broad variety of biochemical functions. Moreover, we did not detect a clear predominance of either cis- or trans- effects on gene expression and none of the 31 eQTLs mapped to QTLs for lipid traits. This finding suggests that detected eQTLs have effects on gene expression but not on

We have used a RNA-seq approach to investigate differential expression in the skeletal muscle of swine (N = 52) with divergent lipid profiles i.e. HIGH (increased intramuscular fat and muscle saturated and monounsaturated fatty acid contents, higher serum lipid concentrations and fatness) and LOW pigs (leaner and with an increased muscle polyunsaturated fatty acid content). The number of mRNAs and non-coding RNAs (ncRNAs) expressed in the porcine gluteus medius muscle were 18,104 and 1,558, respectively. At the nominal level of significance (P-value ≤ 0.05), we detected 1,430 mRNA and 12 non-coding RNA (ncRNA) transcripts as differentially expressed (DE) in the gluteus medius muscle of HIGH vs LOW pigs. This smaller contribution of ncRNAs to differential expression may have biological and technical reasons. We performed a second analysis, that was more stringent (P-value ≤ 0.01 and fold-change ≥ 1.5), and only 96 and 0 mRNA-and ncRNA-encoding genes happened to be DE, respectively. The subset of DE mRNA genes was enriched in pathways related with lipid (lipogenesis and triacylglycerol degradation) and glucose metabolism. Moreover, HIGH pigs showed a more lipogenic profile than their LOW counterparts.

Meat quality traits have an increasing importance in the pig industry because of their strong impact on consumer acceptance. Herewith, we have combined phenotypic and microarray expression data to map loci with potential effects on five meat quality traits recorded in the longissimus dorsi (LD) and gluteus medius (GM) muscles of 350 Duroc pigs, i.e. pH at 24 hours post-mortem (pH24), electric conductivity (CE) and muscle redness (a*), lightness (L*) and yellowness (b*). We have found significant genome-wide associations for CE of LD on SSC4 (~104 Mb), SSC5 (~15 Mb) and SSC13 (~137 Mb), while several additional regions were significantly associated with meat quality traits at the chromosome-wide level. There was a low positional concordance between the associations found for LD and GM traits, a feature that reflects the existence of differences in the genetic determinism of meat quality phenotypes in these two muscles. The performance of an eQTL search for SNPs mapping to the regions associated with meat quality traits demonstrated that the GM a* SSC3 and pH24 SSC17 QTL display positional concordance with cis-eQTL regulating the expression of several genes with a potential role on muscle metabolism.

We performed a genome-wide association study to map the genetic determinants of carcass traits in 350 Duroc pigs typed with the Porcine SNP60 BeadChip. Association analyses were carried out using the gemma software. The proportion of phenotypic variance explained by the SNPs ranged between negligible to moderate (urn:x-wiley:02689146:media:age12545:age12545-math-0001= 0.01–0.30) depending on the trait under consideration. At the genome-wide level, we detected one significant association between backfat thickness between the 3rd and 4th ribs and six SNPs mapping to SSC12 (37–40 Mb). We also identified several chromosome-wide significant associations for ham weight (SSC11: 51–53 Mb, three SNPs; 67–68 Mb, two SNPs), carcass weight (SSC11: 66–68 Mb, two SNPs), backfat thickness between the 3rd and 4th ribs (SSC12: 21 Mb, one SNP; 33–40 Mb, 17 SNPs; 51–58 Mb, two SNPs), backfat thickness in the last rib (SSC12: 37 Mb, one SNP; 40–41 Mb, nine SNPs) and lean meat content (SSC13: 34 Mb, three SNPs and SSC16: 45.1 Mb, one SNP; 62–63 Mb, 10 SNPs; 71–75 Mb, nine SNPs). The ham weight trait-associated region on SSC11 contains two genes (UCHL3 and LMO7) related to muscle development. In addition, the ACACA gene, which encodes an enzyme for the catalysis of fatty acid synthesis, maps to the SSC12 (37–41 Mb) region harbouring trait-associated regions for backfat thickness traits. Sequencing of these candidate genes may help to uncover the causal mutations responsible for the associations found in the present study.

A genome-wide association analysis in a Duroc pig population allowed us detecting a genomic region on pig chromosome 6 (141–147 Mb) that was associated with serum cholesterol (CHOL), triglyceride (TRIG) and low-density lipoprotein (LDL) concentrations. This region contains the proprotein convertase subtilisin-like kexin type 9 (PCSK9) gene (SSC6, 145 Mb), which has a key role in the regulation of CD36, LDL receptor and very low density lipoprotein (VLDL) receptor levels. In the current work, we have genotyped by pyrosequencing a missense PCSK9 c.1222G>A mutation (E408K) in 273 Duroc pigs. The performance of an association analysis with the GEMMA software did not reveal any association between PCSK9 genotype and serum lipid concentrations, evidencing that this polymorphism is not the causal mutation of the CHOL, TRIG, and LDL SSC6 QTL. However, we detected an association, that was highly significant at the nominal level, between PCSK9 genotype and palmitelaidic content at the gluteus medius muscle (P-value = 0.008). There is evidence that PCSK9 induces the degradation of CD36, a key long-chain fatty acid transporter, and that it may decrease the uptake of palmitate. However, the E408K polymorphism analysed in the current work is not predicted to be deleterious, suggesting that the associations found are probably due to the linkage of this polymorphism with a causal mutation yet to be found.

[ES] Se realizó un análisis de asociación genómico, en cerdos Duroc, con los programas GenABEL y EMMAX para caracteres de calidad de la carne y de la grasa intramuscular medidos en los músculos longissimus dorsi y gluteus medius. Las principales asociaciones corresponden al porcentaje de ácido esteárico en los cromosomas 4 y 14., [EN] We performed a genome-wide association analysis in Duroc pigs with GenABEL and EMMAX programs in characters of meat quality and intramuscular fat, measured in the longissimus dorsi and gluteus medius muscle. The main associations correspond to the percentage of stearic acid in chromosomes 4 and 14.

[Background]: The genetic determinism of blood lipid concentrations, the main risk factor for atherosclerosis, is practically unknown in species other than human and mouse. Even in model organisms, little is known about how the genetic determinants of lipid traits are modulated by age-specific factors. To gain new insights into this issue, we have carried out a genome-wide association study (GWAS) for cholesterol (CHOL), triglyceride (TRIG) and low (LDL) and high (HDL) density lipoprotein concentrations measured in Duroc pigs at two time points (45 and 190 days)., [Results]: Analysis of data with mixed-model methods (EMMAX, GEMMA, GenABEL) and PLINK showed a low positional concordance between trait-associated regions (TARs) for serum lipids at 45 and 190 days. Besides, the proportion of phenotypic variance explained by SNPs at these two time points was also substantially different. The four analyses consistently detected two regions on SSC3 (124 Mb, CHOL and LDL at 190 days) and SSC6 (135 Mb, CHOL and TRIG at 190 days) with highly significant effects on the porcine blood lipid profile. Moreover, we have found that SNP variation within SSC3, SSC6, SSC10, SSC13 and SSC16 TARs is associated with the expression of several genes mapping to other chromosomes and related to lipid metabolism., [Conclusions]: Our data demonstrate that the effects of genomic determinants influencing lipid concentrations in pigs, as well as the amount of phenotypic variance they explain, are influenced by age-related factors.