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.猪是探究人类疾病生物学遗传与分子机制的经典动物模型，其在肥胖与代谢性疾病研究中尤为关键——这是因为其他广泛使用的模型（如小鼠）无法完全复现人类相关疾病的关键病理生理特征。为此，本研究构建了F2代猪资源群体（n=564），旨在阐明肥胖与代谢表型背后的遗传机制。通过选用亲本代肥胖性状差异极大的猪品种，确保了肥胖性状在群体中发生分离。研究人员记录了从出生到屠宰（242±48日龄）期间的35项肥胖与代谢表型数据，其中包括在约2月龄（63±10日龄）时通过双能X线吸收法（dual-energy x-ray absorptiometry, DXA）检测的身体组成指标。所有试验猪均采用Illumina猪60K SNP基因分型芯片进行基因分型，并通过连锁不平衡-连锁联合分析，对采集的表型数据开展全基因组显著性关联分析。本研究共鉴定出229个与肥胖及代谢表型相关的全基因组显著性数量性状基因座（quantitative trait locus, QTL）。随后，研究人员开展了比较分析，以明确人类与猪中已报道的QTL之间的重叠程度。对大量肥胖表型的联合分析，揭示了这些性状背后分子机制的遗传结构，表明调控相似表型的QTL在基因组中呈聚集分布。本研究进一步证实，遗传异质性是肥胖性状的固有特征，其成因大概率为不同群体中细胞通路相关组分的不同变异发生了分离或固定。研究团队同时鉴定出了既往人类肥胖研究中报道的多个关键基因，以及一批全新的肥胖相关基因。综上，本研究为深化人类肥胖相关分子机制的认知提供了全新视角。