7,287 research outputs found
Multiple Quantitative Trait Analysis Using Bayesian Networks
Models for genome-wide prediction and association studies usually target a
single phenotypic trait. However, in animal and plant genetics it is common to
record information on multiple phenotypes for each individual that will be
genotyped. Modeling traits individually disregards the fact that they are most
likely associated due to pleiotropy and shared biological basis, thus providing
only a partial, confounded view of genetic effects and phenotypic interactions.
In this paper we use data from a Multiparent Advanced Generation Inter-Cross
(MAGIC) winter wheat population to explore Bayesian networks as a convenient
and interpretable framework for the simultaneous modeling of multiple
quantitative traits. We show that they are equivalent to multivariate genetic
best linear unbiased prediction (GBLUP), and that they are competitive with
single-trait elastic net and single-trait GBLUP in predictive performance.
Finally, we discuss their relationship with other additive-effects models and
their advantages in inference and interpretation. MAGIC populations provide an
ideal setting for this kind of investigation because the very low population
structure and large sample size result in predictive models with good power and
limited confounding due to relatedness.Comment: 28 pages, 1 figure, code at
http://www.bnlearn.com/research/genetics1
Bayesian Approximate Kernel Regression with Variable Selection
Nonlinear kernel regression models are often used in statistics and machine
learning because they are more accurate than linear models. Variable selection
for kernel regression models is a challenge partly because, unlike the linear
regression setting, there is no clear concept of an effect size for regression
coefficients. In this paper, we propose a novel framework that provides an
effect size analog of each explanatory variable for Bayesian kernel regression
models when the kernel is shift-invariant --- for example, the Gaussian kernel.
We use function analytic properties of shift-invariant reproducing kernel
Hilbert spaces (RKHS) to define a linear vector space that: (i) captures
nonlinear structure, and (ii) can be projected onto the original explanatory
variables. The projection onto the original explanatory variables serves as an
analog of effect sizes. The specific function analytic property we use is that
shift-invariant kernel functions can be approximated via random Fourier bases.
Based on the random Fourier expansion we propose a computationally efficient
class of Bayesian approximate kernel regression (BAKR) models for both
nonlinear regression and binary classification for which one can compute an
analog of effect sizes. We illustrate the utility of BAKR by examining two
important problems in statistical genetics: genomic selection (i.e. phenotypic
prediction) and association mapping (i.e. inference of significant variants or
loci). State-of-the-art methods for genomic selection and association mapping
are based on kernel regression and linear models, respectively. BAKR is the
first method that is competitive in both settings.Comment: 22 pages, 3 figures, 3 tables; theory added; new simulations
presented; references adde
Bivariate causal mixture model quantifies polygenic overlap between complex traits beyond genetic correlation.
Accumulating evidence from genome wide association studies (GWAS) suggests an abundance of shared genetic influences among complex human traits and disorders, such as mental disorders. Here we introduce a statistical tool, MiXeR, which quantifies polygenic overlap irrespective of genetic correlation, using GWAS summary statistics. MiXeR results are presented as a Venn diagram of unique and shared polygenic components across traits. At 90% of SNP-heritability explained for each phenotype, MiXeR estimates that 8.3 K variants causally influence schizophrenia and 6.4 K influence bipolar disorder. Among these variants, 6.2 K are shared between the disorders, which have a high genetic correlation. Further, MiXeR uncovers polygenic overlap between schizophrenia and educational attainment. Despite a genetic correlation close to zero, the phenotypes share 8.3 K causal variants, while 2.5 K additional variants influence only educational attainment. By considering the polygenicity, discoverability and heritability of complex phenotypes, MiXeR analysis may improve our understanding of cross-trait genetic architectures
Novel Bayesian Networks for Genomic Prediction of Developmental Traits in Biomass Sorghum.
The ability to connect genetic information between traits over time allow Bayesian networks to offer a powerful probabilistic framework to construct genomic prediction models. In this study, we phenotyped a diversity panel of 869 biomass sorghum (Sorghum bicolor (L.) Moench) lines, which had been genotyped with 100,435 SNP markers, for plant height (PH) with biweekly measurements from 30 to 120 days after planting (DAP) and for end-of-season dry biomass yield (DBY) in four environments. We evaluated five genomic prediction models: Bayesian network (BN), Pleiotropic Bayesian network (PBN), Dynamic Bayesian network (DBN), multi-trait GBLUP (MTr-GBLUP), and multi-time GBLUP (MTi-GBLUP) models. In fivefold cross-validation, prediction accuracies ranged from 0.46 (PBN) to 0.49 (MTr-GBLUP) for DBY and from 0.47 (DBN, DAP120) to 0.75 (MTi-GBLUP, DAP60) for PH. Forward-chaining cross-validation further improved prediction accuracies of the DBN, MTi-GBLUP and MTr-GBLUP models for PH (training slice: 30-45 DAP) by 36.4-52.4% relative to the BN and PBN models. Coincidence indices (target: biomass, secondary: PH) and a coincidence index based on lines (PH time series) showed that the ranking of lines by PH changed minimally after 45 DAP. These results suggest a two-level indirect selection method for PH at harvest (first-level target trait) and DBY (second-level target trait) could be conducted earlier in the season based on ranking of lines by PH at 45 DAP (secondary trait). With the advance of high-throughput phenotyping technologies, our proposed two-level indirect selection framework could be valuable for enhancing genetic gain per unit of time when selecting on developmental traits
Sparse reduced-rank regression for imaging genetics studies: models and applications
We present a novel statistical technique; the sparse reduced rank regression (sRRR) model
which is a strategy for multivariate modelling of high-dimensional imaging responses and
genetic predictors. By adopting penalisation techniques, the model is able to enforce sparsity
in the regression coefficients, identifying subsets of genetic markers that best explain
the variability observed in subsets of the phenotypes. To properly exploit the rich structure
present in each of the imaging and genetics domains, we additionally propose the use of
several structured penalties within the sRRR model. Using simulation procedures that accurately
reflect realistic imaging genetics data, we present detailed evaluations of the sRRR
method in comparison with the more traditional univariate linear modelling approach. In
all settings considered, we show that sRRR possesses better power to detect the deleterious
genetic variants. Moreover, using a simple genetic model, we demonstrate the potential
benefits, in terms of statistical power, of carrying out voxel-wise searches as opposed to
extracting averages over regions of interest in the brain. Since this entails the use of phenotypic
vectors of enormous dimensionality, we suggest the use of a sparse classification
model as a de-noising step, prior to the imaging genetics study. Finally, we present the
application of a data re-sampling technique within the sRRR model for model selection.
Using this approach we are able to rank the genetic markers in order of importance of association
to the phenotypes, and similarly rank the phenotypes in order of importance to
the genetic markers. In the very end, we illustrate the application perspective of the proposed
statistical models in three real imaging genetics datasets and highlight some potential
associations
- …