Rohart, F. | bioRxiv Science

bioRxiv2020

Estimation of non-additive genetic variance in human complex traits from a large sample of unrelated individuals

Non-additive genetic variance for complex traits is traditionally estimated from data on relatives. It is notoriously difficult to estimate without bias in non-laboratory species, including humans, because of possible confounding with environmental covariance among relatives. In principle, non-additive variance attributable to common DNA variants can be estimated from a random sample of unrelated individuals with genome-wide SNP data. Here, we jointly estimate the proportion of variance explained by additive [Formula], dominance [Formula] and additive-by-additive [Formula] genetic variance in a single analysis model. We first show by simulations that our model leads to unbiased estimates and provide new theory to predict standard errors estimated using either least squares or maximum likelihood. We then apply the model to 70 complex traits using 254,679 unrelated individuals from the UK Biobank and 1.1M genotyped and imputed SNPs. We found strong evidence for additive variance (average across traits [Formula]. In contrast, the average estimate of [Formula] across traits was 0.001, implying negligible dominance variance at causal variants tagged by common SNPs. The average epistatic variance [Formula] across the traits was 0.058, not significantly different from zero because of the large sampling variance. Our results provide new evidence that genetic variance for complex traits is predominantly additive, and that sample sizes of many millions of unrelated individuals are needed to estimate epistatic variance with sufficient precision.

genetics↗

bioRxiv2017

mixOmics: an R package for ‘omics feature selection and multiple data integration

The advent of high throughput technologies has led to a wealth of publicly available omics data coming from different sources, such as transcriptomics, proteomics, metabolomics. Combining such large-scale biological data sets can lead to the discovery of important biological insights, provided that relevant information can be extracted in a holistic manner. Current statistical approaches have been focusing on identifying small subsets of molecules (a molecular signature) to explain or predict biological conditions, but mainly for a single type of omics. In addition, commonly used methods are univariate and consider each biological feature independently.\n\nWe introduce mixOmics, an R package dedicated to the multivariate analysis of biological data sets with a specific focus on data exploration, dimension reduction and visualisation. By adopting a system biology approach, the toolkit provides a wide range of methods that statistically integrate several data sets at once to probe relationships between heterogeneous omics data sets. Our recent methods extend Projection to Latent Structure (PLS) models for discriminant analysis, for data integration across multiple omics data or across independent studies, and for the identification of molecular signatures. We illustrate our latest mixOmics integrative frameworks for the multivariate analyses of omics data available from the package.

bioinformatics↗