scholarly journals Implications of simplified linkage equilibrium SNP simulation

2015 ◽  
Author(s):  
Sang Hong Lee

In a recent paper published in PNAS (Golan et al. 2014), residual maximum likelihood (REML) seriously underestimated genetic variance explained by genomewide single nucleotide polymorphism when using a case-control design. It was concluded that Haseman–Elston regression (denoted as PCGC in their paper) should be used instead of REML. Their conclusions were based on results from simplified linkage equilibrium SNP simulation (SLES), which the authors acknowledged may be unrealistic. We found that their simulation, SLES, unrealistically inflated the correlation between the eigenvectors of the genomic relationship matrix and disease status to values that are rarely observed in real data analyses. With a more realistic simulation that the authors failed to carry out (as they noted in their paper), we showed that there was no such inflated correlation between the eigenvectors of the genomic relationship matrix and disease status. Because REML uses the eigensystem of covariance structure, the inflated correlation artefactually constrained its estimates. We compared SNP-heritabilities from SLES and a more realistic simulation, showing that there was a substantial difference between the REML estimates from the two simulation strategies. Finally, we presented that there was no difference between REML and PCGC in real data analyses. This pattern from real data results differed strikingly from the pattern in the simulation study of Golan et al. One needs to be cautious of results drawn from SLES.

Genes ◽  
2019 ◽  
Vol 10 (11) ◽  
pp. 922
Author(s):  
Ling-Yun Chang ◽  
Sajjad Toghiani ◽  
El Hamidi Hay ◽  
Samuel E. Aggrey ◽  
Romdhane Rekaya

A dramatic increase in the density of marker panels has been expected to increase the accuracy of genomic selection (GS), unfortunately, little to no improvement has been observed. By including all variants in the association model, the dimensionality of the problem should be dramatically increased, and it could undoubtedly reduce the statistical power. Using all Single nucleotide polymorphisms (SNPs) to compute the genomic relationship matrix (G) does not necessarily increase accuracy as the additive relationships can be accurately estimated using a much smaller number of markers. Due to these limitations, variant prioritization has become a necessity to improve accuracy. The fixation index (FST) as a measure of population differentiation has been used to identify genome segments and variants under selection pressure. Using prioritized variants has increased the accuracy of GS. Additionally, FST can be used to weight the relative contribution of prioritized SNPs in computing G. In this study, relative weights based on FST scores were developed and incorporated into the calculation of G and their impact on the estimation of variance components and accuracy was assessed. The results showed that prioritizing SNPs based on their FST scores resulted in an increase in the genetic similarity between training and validation animals and improved the accuracy of GS by more than 5%.


2019 ◽  
Vol 51 (1) ◽  
Author(s):  
Pascal Duenk ◽  
Mario P. L. Calus ◽  
Yvonne C. J. Wientjes ◽  
Vivian P. Breen ◽  
John M. Henshall ◽  
...  

Following publication of original article [1], we noticed that there was an error: Eq. (3) on page 5 is the genomic relationship matrix that


2018 ◽  
Vol 53 (6) ◽  
pp. 717-726 ◽  
Author(s):  
Michel Marques Farah ◽  
Marina Rufino Salinas Fortes ◽  
Matthew Kelly ◽  
Laercio Ribeiro Porto-Neto ◽  
Camila Tangari Meira ◽  
...  

Abstract: The objective of this work was to evaluate the effects of genomic information on the genetic evaluation of hip height in Brahman cattle using different matrices built from genomic and pedigree data. Hip height measurements from 1,695 animals, genotyped with high-density SNP chip or imputed from 50 K high-density SNP chip, were used. The numerator relationship matrix (NRM) was compared with the H matrix, which incorporated the NRM and genomic relationship (G) matrix simultaneously. The genotypes were used to estimate three versions of G: observed allele frequency (HGOF), average minor allele frequency (HGMF), and frequency of 0.5 for all markers (HG50). For matrix comparisons, animal data were either used in full or divided into calibration (80% older animals) and validation (20% younger animals) datasets. The accuracy values for the NRM, HGOF, and HG50 were 0.776, 0.813, and 0.594, respectively. The NRM and HGOF showed similar minor variances for diagonal and off-diagonal elements, as well as for estimated breeding values. The use of genomic information resulted in relationship estimates similar to those obtained based on pedigree; however, HGOF is the best option for estimating the genomic relationship matrix and results in a higher prediction accuracy. The ranking of the top 20% animals was very similar for all matrices, but the ranking within them varies depending on the method used.


2020 ◽  
Vol 10 (6) ◽  
pp. 2069-2078 ◽  
Author(s):  
Christos Palaiokostas ◽  
Shannon M. Clarke ◽  
Henrik Jeuthe ◽  
Rudiger Brauning ◽  
Timothy P. Bilton ◽  
...  

Arctic charr (Salvelinus alpinus) is a species of high economic value for the aquaculture industry, and of high ecological value due to its Holarctic distribution in both marine and freshwater environments. Novel genome sequencing approaches enable the study of population and quantitative genetic parameters even on species with limited or no prior genomic resources. Low coverage genotyping by sequencing (GBS) was applied in a selected strain of Arctic charr in Sweden originating from a landlocked freshwater population. For the needs of the current study, animals from year classes 2013 (171 animals, parental population) and 2017 (759 animals; 13 full sib families) were used as a template for identifying genome wide single nucleotide polymorphisms (SNPs). GBS libraries were constructed using the PstI and MspI restriction enzymes. Approximately 14.5K SNPs passed quality control and were used for estimating a genomic relationship matrix. Thereafter a wide range of analyses were conducted in order to gain insights regarding genetic diversity and investigate the efficiency of the genomic information for parentage assignment and breeding value estimation. Heterozygosity estimates for both year classes suggested a slight excess of heterozygotes. Furthermore, FST estimates among the families of year class 2017 ranged between 0.009 – 0.066. Principal components analysis (PCA) and discriminant analysis of principal components (DAPC) were applied aiming to identify the existence of genetic clusters among the studied population. Results obtained were in accordance with pedigree records allowing the identification of individual families. Additionally, DNA parentage verification was performed, with results in accordance with the pedigree records with the exception of a putative dam where full sib genotypes suggested a potential recording error. Breeding value estimation for juvenile growth through the usage of the estimated genomic relationship matrix clearly outperformed the pedigree equivalent in terms of prediction accuracy (0.51 opposed to 0.31). Overall, low coverage GBS has proven to be a cost-effective genotyping platform that is expected to boost the selection efficiency of the Arctic charr breeding program.


Genetics ◽  
2020 ◽  
Vol 216 (3) ◽  
pp. 651-669
Author(s):  
Yong Jiang ◽  
Jochen C. Reif

The genomic relationship matrix plays a key role in the analysis of genetic diversity, genomic prediction, and genome-wide association studies. The epistatic genomic relationship matrix is a natural generalization of the classic genomic relationship matrix in the sense that it implicitly models the epistatic effects among all markers. Calculating the exact form of the epistatic relationship matrix requires high computational load, and is hence not feasible when the number of markers is large, or when high-degree of epistasis is in consideration. Currently, many studies use the Hadamard product of the classic genomic relationship matrix as an approximation. However, the quality of the approximation is difficult to investigate in the strict mathematical sense. In this study, we derived iterative formulas for the precise form of the epistatic genomic relationship matrix for arbitrary degree of epistasis including both additive and dominance interactions. The key to our theoretical results is the observation of an interesting link between the elements in the genomic relationship matrix and symmetric polynomials, which motivated the application of the corresponding mathematical theory. Based on the iterative formulas, efficient recursive algorithms were implemented. Compared with the approximation by the Hadamard product, our algorithms provided a complete solution to the problem of calculating the exact epistatic genomic relationship matrix. As an application, we showed that our new algorithms easily relieved the computational burden in a previous study on the approximation behavior of two limit models.


2018 ◽  
Vol 97 (1) ◽  
pp. 35-42 ◽  
Author(s):  
Kirsty Lee Moore ◽  
Conrad Vilela ◽  
Karolina Kaseja ◽  
Raphael Mrode ◽  
Mike Coffey

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