Quantitative genetics theory for genomic selection and efficiency of genotypic value prediction in open-pollinated populations

ABSTRACT: Quantitative genetics theory for genomic selection has mainly focused on additive effects. This study presents quantitative genetics theory applied to genomic selection aiming to prove that prediction of genotypic value based on thousands of single nucleotide polymorphisms (SNPs) depends on linkage disequilibrium (LD) between markers and QTLs, assuming dominance and epistasis. Based on simulated data, we provided information on dominance and genotypic value prediction accuracy, assuming mass selection in an open-pollinated population, all quantitative trait loci (QTLs) of lower effect, and reduced sample size. We show that the predictor of dominance value is proportional to the square of the LD value and to the dominance deviation for each QTL that is in LD with each marker. The weighted (by the SNP frequencies) dominance value predictor has greater accuracy than the unweighted predictor. The linear × linear, linear × quadratic, quadratic × linear, and quadratic × quadratic SNP effects are proportional to the corresponding linear combinations of epistatic effects for QTLs and the LD values. LD between two markers with a common QTL causes a bias in the prediction of epistatic values. Compared to phenotypic selection, the efficiency of genomic selection for genotypic value prediction increases as trait heritability decreases. The degree of dominance did not affect the genotypic value prediction accuracy and the approach to maximum accuracy is asymptotic with increases in SNP density. The decrease in the sample size from 500 to 200 did not markedly reduce the genotypic value prediction accuracy

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

New insights into the genetic etiology of Alzheimer’s disease and related dementias

Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele. © 2022, The Author(s)