Data from: Comparative analyses of QTLs influencing obesity and metabolic phenotypes in pigs and humans

The pig is a well-known animal model used to investigate genetic and mechanistic aspects of human disease biology. They are particularly useful in the context of obesity and metabolic diseases because other widely used models (e.g. mice) do not completely recapitulate key pathophysiological features associated with these diseases in humans. Therefore, we established a F2 pig resource population (n = 564) designed to elucidate the genetics underlying obesity and metabolic phenotypes. Segregation of obesity traits was ensured by using breeds highly divergent with respect to obesity traits in the parental generation. Several obesity and metabolic phenotypes were recorded (n = 35) from birth to slaughter (242 ± 48 days), including body composition determined at about two months of age (63 ± 10 days) via dual-energy x-ray absorptiometry (DXA) scanning. All pigs were genotyped using Illumina Porcine 60k SNP Beadchip and a combined linkage disequilibrium-linkage analysis was used to identify genome-wide significant associations for collected phenotypes. We identified 229 QTLs which associated with adiposity- and metabolic phenotypes at genome-wide significant levels. Subsequently comparative analyses were performed to identify the extent of overlap between previously identified QTLs in both humans and pigs. The combined analysis of a large number of obesity phenotypes has provided insight in the genetic architecture of the molecular mechanisms underlying these traits indicating that QTLs underlying similar phenotypes are clustered in the genome. Our analyses have further confirmed that genetic heterogeneity is an inherent characteristic of obesity traits most likely caused by segregation or fixation of different variants of the individual components belonging to cellular pathways in different populations. Several important genes previously associated to obesity in human studies, along with novel genes were identified. Altogether, this study provides novel insight that may further the current understanding of the molecular mechanisms underlying human obesity

Comparative Analyses of QTLs Influencing Obesity and Metabolic Phenotypes in Pigs and Humans

International audienceThe pig is a well-known animal model used to investigate genetic and mechanistic aspects of human disease biology. They are particularly useful in the context of obesity and metabolic diseases because other widely used models (e.g. mice) do not completely recapitulate key pathophysiological features associated with these diseases in humans. Therefore, we established a F2 pig resource population (n = 564) designed to elucidate the genetics underlying obesity and metabolic phenotypes. Segregation of obesity traits was ensured by using breeds highly divergent with respect to obesity traits in the parental generation. Several obesity and metabolic phenotypes were recorded (n = 35) from birth to slaughter (242 ± 48 days), including body composition determined at about two months of age (63 ± 10 days) via dual-energy x-ray absorptiometry (DXA) scanning. All pigs were genotyped using Illumina Porcine 60k SNP Beadchip and a combined linkage disequilibrium-linkage analysis was used to identify genome-wide significant associations for collected phenotypes. We identified 229 QTLs which associated with adiposity- and metabolic phenotypes at genome-wide significant levels. Subsequently comparative analyses were performed to identify the extent of overlap between previously identified QTLs in both humans and pigs. The combined analysis of a large number of obesity phenotypes has provided insight in the genetic architecture of the molecular mechanisms underlying these traits indicating that QTLs underlying similar phenotypes are clustered in the genome. Our analyses have further confirmed that genetic heterogeneity is an inherent characteristic of obesity traits most likely caused by segregation or fixation of different variants of the individual components belonging to cellular pathways in different populations. Several important genes previously associated to obesity in human studies, along with novel genes were identified. Altogether, this study provides novel insight that may further the current understanding of the molecular mechanisms underlying human obesity

Chromosomal positions associated with multiple phenotypes in the pig resource population.

<p>Chromosomal positions associated with multiple phenotypes in the pig resource population.</p

Porcine QTLs with overlapping QTLs for related phenotypes in the NHGRI GWAS catalog.

<p>Porcine QTLs with overlapping QTLs for related phenotypes in the NHGRI GWAS catalog.</p

Description of phenotypes measured in pigs at different ages, and covariates used in the statistical model for association analyses.

<p><i>Age 1</i>: <i>63 ± 10 days; Age 2</i>: <i>218 ± 45 days; Age 3</i>: <i>242 ± 48 days</i></p><p>Description of phenotypes measured in pigs at different ages, and covariates used in the statistical model for association analyses.</p

Genetic variance of BMI in F2 population.

<p>(A) Yorkshire (B) Minipig (C) Duroc are representative images of pig breeds used to create the F2 resource population. D-G are representative images of animals from the F2 population. H represents the distribution of BMI in F2 pigs measured at 220 ± 45 days. (Photos: A and C courtesy DanBred; B courtesy Ellegaard Göttingen Minipigs; D, E, F, G courtesy Thomas Jakob Olsen).</p

QTLs influencing Obesity related Phenotypes in pigs.

<p>Fig 2. (Figure created using Phenogram- <a href="http://visualization.ritchielab.psu.edu/phenograms/plot" target="_blank">http://visualization.ritchielab.psu.edu/phenograms/plot</a>). Vertical columns labeled 1–18 represent porcine autosomes SSC1–18. QTL locations are marked on the chromosomes using a proximity algorithm that minimizes the overlap between individual QTLs for different phenotypes. Different phenotypes are represented by circles filled with different colors. The description of the abbreviated phenotypes is presented in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0137356#pone.0137356.t001" target="_blank">Table 1</a>.</p

UNIK_Porcine_FinalReport

Original SNP genotypes for alle individuals included for 'Comparative Analyses of QTLs influencing Obesity and Metabolic Phenotypes in Pigs and Humans', Pant et al. Plos ONE 201