13 Oral - Platform Session 1 Complex Traits
Wednesday June 08, 11:20 AM - 11:35 AM

Authors:
Leilei Cui ^1,2,3; Bin Yang ¹; Shijun Xiao ¹; Jun Gao ¹; Amelie Baud ⁴; Jonathan Flint ⁵; Richard Mott ²; Lusheng Huang ¹

Affiliations:
1) Jiangxi Agriculture University, Nanchang, China; 2) UCL Genetics Institute, London, UK; 3) Nanchang University, Nanchang, China; 4) European Molecular Biology Laboratory, European Bioinformatics Institute, Cambridge, UK; 5) Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, UCLA, Los Angeles, US

Keywords:
Complex traits

Dominance arises from the interaction between different alleles within the same genomic locus, which historically played a major role in the study of biological traits. However, today most genome-wide association studies (GWAS) generally ignore dominance effects. This might bias and hinder our understanding of the mechanism and architecture of complex traits, and potentially fail to detect dominant quantitative trait loci (QTLs). In this study, we surveyed the dominance effect contributions to genetic architecture across many organismal and gene expression traits across three outbred mammalian populations: the White Duroc x Erhualian pig F2 intercross stock (n=1,005), the rat heterogeneous stock (n=1,407) and the mouse heterogeneous stock (n=2,002). We estimated additive and dominance variance components for each trait based on the whole genome SNPs, then performed GWAS by fitting both additive and dominance effects at each SNP using our newly developed software ADDO. We further mapped gene expression QTLs (eQTLs) of different tissues in all populations, and also investigated the relationship between their inheritance modes and regulation types. On average dominance accounted for 11% (from 0% to 57%) phenotypic variances in pigs, about one-third of the additive contributions, and similar to that observed in rats and mice. Interestingly, traits related to hematology and immunology generally tend to have a high dominance variance. We identified 157, 66 and 60 novel loci showing significant complete dominance or overdominance effects in pigs, rats and mice. The proportions of QTL types across these three species are similar: 55.6% (additive): 16.1% (complete dominance): 28.3% (overdominance). Most strikingly, across all populations, cis-acting eQTLs are predominantly additive while trans-acting eQTLs are enriched for dominance effects. A search for genes causal for dominance physiological QTLs revealed these are unlikely to be physically linked to the QTLs but instead are associated via trans-acting dominance eQTLs. This study suggests that the dominance effect contribution to the genetic architecture of complex traits in mammals is both important and has a distinct mechanism from additive contributions.