An F2 Pig Resource Population as a Model for Genetic Studies of Obesity and Obesity-Related Diseases in Humans: Design and Genetic Parameters

Lisette J A Kogelman,Susanna Cirera,Haja N Kadarmideen,Claus B Jørgensen,Thomas Mark,Mette J Jacobsen,Peter Karlskov-Mortensen,Camilla S Bruun,Merete Fredholm

doi:10.3389/fgene.2013.00029

Abstract

Obesity is a rising worldwide public health problem. Difficulties to precisely measure various obesity traits and the genetic heterogeneity in human have been major impediments to completely disentangle genetic factors causing obesity. The pig is a relevant model for studying human obesity and obesity-related (OOR) traits. Using founder breeds divergent with respect to obesity traits we have created an F2 pig resource population (454 pigs), which has been intensively phenotyped for 36 OOR traits. The main rationale for our study is to characterize the genetic architecture of OOR traits in the F2 pig design, by estimating heritabilities, genetic, and phenotypic correlations using mixed- and multi-trait BLUP animal models. Our analyses revealed high coefficients of variation (15–42%) and moderate to high heritabilities (0.22–0.81) in fatness traits, showing large phenotypic and genetic variation in the F2 population, respectively. This fulfills the purpose of creating a resource population divergent for OOR traits. Strong genetic correlations were found between weight and lean mass at dual-energy x-ray absorptiometry scanning (0.56–0.97). Weight and conformation also showed strong genetic correlations with slaughter traits (e.g., rg between abdominal circumference and leaf fat at slaughtering: 0.66). Genetic correlations between fat-related traits and the glucose level vary between 0.35 and 0.74 and show a strong correlation between adipose tissue and impaired glucose metabolism. Our power calculations showed a minimum of 80% power for QTL detection for all phenotypes. We revealed genetic correlations at population level, for the first time, for several difficult to measure and novel OOR traits and diseases. The results underpin the potential of the established F2 pig resource population for further genomic, systems genetics, and functional investigations to unravel the genetic background of OOR traits.

Highlights

Obesity is a growing worldwide public health problem with a prevalence that has almost doubled between 1980 and 2008 (World Health Organization, 2012), resulting in one of the most significant public health challenges of the twenty-first century
The results underpin the potential of the established F2 pig resource population for further genomic, systems genetics, and functional investigations to unravel the genetic background of obesity and obesity-related (OOR) traits
Quantitative trait loci mapping or genome-wide association studies (GWAS) requires a thorough knowledge on genetic variances and any relationships amongst traits that are investigated, if such parameters for novel traits have not yet been reported elsewhere

Summary

Introduction

Obesity is a growing worldwide public health problem with a prevalence that has almost doubled between 1980 and 2008 (World Health Organization, 2012), resulting in one of the most significant public health challenges of the twenty-first century. A deeper insight into the genetic background and, in turn, novel metabolic molecular pathways will help to explain why some people are susceptible to obesity whereas others remain lean. This could lead to improvement of prevention, therapy, and treatment of obesity and obesity-related (OOR) diseases (Farooqi and O’Rahilly, 2007)

Methods

Results

Conclusion