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Biology subjects

Momin, M. M.

Publications and source records attributed to Momin, M. M..

3 recordsLinked to original sources

A novel hyper-parameter can increase the prediction accuracy in a single-step genetic evaluation

The H-matrix best linear unbiased prediction (HBLUP) method has been widely used in livestock breeding programs. It can integrate all information, including pedigree, genotypes, and phenotypes on both genotyped and non-genotyped individuals into one single evaluation that can provide reliable predictions of breeding values. The existing HBLUP method (e.g., that implemented in BLUPf90 software) requires hyper-parameters that should be adequately optimised as otherwise the genomic prediction accuracy may decrease. In this study, we assess the performance of HBLUP using various hyper-parameters such as blending, tuning and scale factor in simulated as well as real data on Hanwoo cattle. In both simulated and cattle data, we show that blending is not necessary, indicating that the prediction accuracy decreases when using a blending hyper-parameter < 1. The tuning process (adjusting genomic relationships accounting for base allele frequencies) improves prediction accuracy in the simulated data, confirming previous studies, although the improvement is not statistically significant in the Hanwoo cattle data. We also demonstrate that a scale factor, , which determines the relationship between allele frequency and per-allele effect size, can improve the HBLUP accuracy in both simulated and real data. Our findings suggest that an optimal scale factor should be considered to increase the prediction accuracy, in addition to blending and tuning processes, when using HBLUP. Author SummaryDespite significant advancements in genotyping technologies, the capability to predict the phenotypes of complex traits is still limited. H-matrix best linear unbiased prediction (HBLUP) method has been used to tackle this limitation to demonstrate a promising prediction accuracy. However, the performance of HBLUP depends heavily on the optimisation of hyper-parameters (e.g. blending and tuning). In this study, we introduce a scale factor (), as a new hyper-parameter in HBLUP, which accounts for the relationship between allele frequency and per-allele effect size. Using simulation and real data analysis, we investigate the impact of the hyper-parameters (blending, tuning, and scale factor) on the performance of HBLUP. In general, the blending process may not improve the prediction accuracy for simulation and cattle data although a marginally improved prediction accuracy is observed with a blending hyper-parameter = 0.86 for one of carcass traits in the cattle data. In contrast, the tuning process can increase the HBLUP accuracy particularly in simulated data. Furthermore, we observe that an optimal scale factor plays a significant role in improving the prediction accuracy in both simulated and real data, and the improvement is relatively large compared with blending and tuning processes. In this context, we propose considering the scale factor as a hyper-parameter to increase the predictive performance of HBLUP.

genomics↗

Significance tests for R2 of out-of-sample prediction using polygenic scores

The coefficient of determination (R2) is a well-established measure to indicate the predictive ability of polygenic scores (PGS). However, the sampling variance of R2 is rarely considered so that 95% confidence intervals (CI) are not usually reported. Moreover, when comparisons are made between PGS based on different discovery samples, the sampling covariance of R2 is necessary to test the difference between them. Here, we show how to estimate the variance and covariance of R2 values to assess the 95% CI and p-value of the R2 difference. We apply this approach to real data to predict into 28,880 European participants using UK Biobank (UKBB) and Biobank Japan (BBJ) GWAS summary statistics for cholesterol and BMI. We quantify the significantly higher predictive ability of UKBB PGS compared to BBJ PGS (p-value 7.6e-31 for cholesterol and 1.4e-50 for BMI). A joint model of UKBB and BBJ PGS significantly improves the predictive ability, compared to a model of UKBB PGS only (p-value 3.5e-05 for cholesterol and 1.3e-28 for BMI). The proposed approach can also be applied to testing a significant difference between R2 values across different p-value thresholds. We also show that the predictive ability of regulatory SNPs is significantly enriched than non-regulatory SNPs for cholesterol (p-value 2.6e-19 for UKBB and 8.7e-08 for BBJ). We suggest that the proposed approach (available in R package r2redux) should be used to test the statistical significance of difference between pairs of PGS, which may help to draw a correct conclusion about the predictive ability of PGS.

genetics↗

A novel method for an unbiased estimate of cross-ancestry genetic correlation using individual-level data

Cross-ancestry genetic correlation is an important parameter to understand the genetic relationship between two ancestry groups for a complex trait. However, existing methods cannot properly account for ancestry-specific genetic architecture, which is diverse across ancestries, producing biased estimates of cross-ancestry genetic correlation. Here, we present a method to construct a genomic relationship matrix (GRM) that can correctly account for the relationship between ancestry-specific allele frequencies and ancestry-specific causal effects. Through comprehensive simulations, we show that the proposed method outperforms existing methods in the estimations of SNP-based heritability and cross-ancestry genetic correlation. The proposed method is further applied to six anthropometric traits from the UK Biobank data across 5 ancestry groups. One of our findings is that for obesity, the estimated genetic correlation between African and European ancestry cohorts is significantly different from unity, suggesting that obesity is genetically heterogenous between these two ancestry groups.

genetics↗