scholarly journals Comparing Heritability Estimators under Alternative Structures of Linkage Disequilibrium

2021 ◽  
Author(s):  
Alan Min ◽  
Elizabeth Thompson ◽  
Saonli Basu
Keyword(s):  
Linkage Disequilibrium ◽  
Fixed Effects ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Alternative Structures ◽  
Genome Wide ◽  
Heritability Estimation ◽  
Moments Estimators ◽  
The Impact ◽  
Number Of Individuals

AbstractSNP heritability of a trait is the proportion of its variance explained by the additive effects of the genome-wide single nucleotide polymorphisms (SNPs). The existing approaches to estimate SNP heritability can be broadly classified into two categories. One set of approaches model the SNP effects as fixed effects and the other treats the SNP effects as random effects. These methods make certain assumptions about the dependency among individuals (familial relationship) as well as the dependency among markers (linkage disequilibrium, LD) to provide consistent estimates of SNP heritability as the number of individuals increases. While various approaches have been proposed to account for such dependencies, it remains unclear which estimates reported in the literature are more robust against various model mis-specifications. Here we investigate the impact of different structures of LD and familial relatedness on heritability estimation. We show that the performance of different methods for heritability estimation depends heavily on the structure of the underlying pattern of LD and the degree of relatedness among sampled individuals. However, contrary to the claim in the current literature, we did not find significant differences in the performance of these fixed-SNP-effects and random-SNP-effects approaches. Moreover, we established the equivalence between the two method-of-moments estimators, one from each of these two lines of approaches.

scholarly journals Accuracy of marker-assisted selection with single markers and marker haplotypes in cattle

2007 ◽  
Vol 89 (4) ◽  
pp. 215-220 ◽  
Author(s):  
B. J. HAYES ◽  
A. J. CHAMBERLAIN ◽  
H. McPARTLAN ◽  
I. MACLEOD ◽  
L. SETHURAMAN ◽  
...  
Keyword(s):  
Linkage Disequilibrium ◽  
Quantitative Trait Loci ◽  
Single Nucleotide Polymorphisms ◽  
Quantitative Trait ◽  
Marker Assisted Selection ◽  
Nucleotide Polymorphisms ◽  
Data Set ◽  
Single Nucleotide ◽  
Angus Cattle ◽  
Genome Wide

SummaryA key question for the implementation of marker-assisted selection (MAS) using markers in linkage disequilibrium with quantitative trait loci (QTLs) is how many markers surrounding each QTL should be used to ensure the marker or marker haplotypes are in sufficient linkage disequilibrium (LD) with the QTL. In this paper we compare the accuracy of MAS using either single markers or marker haplotypes in an Angus cattle data set consisting of 9323 genome-wide single nucleotide polymorphisms (SNPs) genotyped in 379 Angus cattle. The extent of LD in the data set was such that the average marker–marker r2 was 0·2 at 200 kb. The accuracy of MAS increased as the number of markers in the haplotype surrounding the QTL increased, although only when the number of markers in the haplotype was 4 or greater did the accuracy exceed that achieved when the SNP in the highest LD with the QTL was used. A large number of phenotypic records (>1000) were required to accurately estimate the effects of the haplotypes.

scholarly journals Re-analysis of a Genome-Wide Gene-By-Environment Interaction Study of Case Parent Trios, Adjusted for Population Stratification

2021 ◽  
Vol 11 ◽  
Author(s):  
Pulindu Ratnasekera ◽  
Brad McNeney
Keyword(s):  
East Asian ◽  
Environment Interaction ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Multivitamin Supplementation ◽  
Gene Environment ◽  
Genome Wide ◽  
A Genome ◽  
The Impact ◽  
East Asian Ancestry

We investigate the impact of confounding on the results of a genome-wide association analysis by Beaty et al., which identified multiple single nucleotide polymorphisms that appeared to modify the effect of maternal smoking, alcohol consumption, or multivitamin supplementation on risk of cleft palate. The study sample of case-parent trios was primarily of European and East Asian ancestry, and the distribution of all three exposures differed by ancestral group. Such differences raise the possibility that confounders, rather than the exposures, are the risk modifiers and hence that the inference of gene-environment (G×E) interaction may be spurious. Our analyses generally confirmed the result of Beaty et al. and suggest the interaction G×E is driven by the European trios, whereas the East Asian trios were less informative.

scholarly journals Increased individual homozygosity is correlated with low fitness in a fragmented lizard population

2019 ◽  
Vol 128 (4) ◽  
pp. 952-962 ◽  
Author(s):  
Javier Pérez-Tris ◽  
Alejandro Llanos-Garrido ◽  
Paul Bloor ◽  
Roberto Carbonell ◽  
José Luis Tellería ◽  
...  
Keyword(s):  
Gene Flow ◽  
Restricted Gene Flow ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Genome Wide ◽  
Anthropogenic Habitat ◽  
Geographical Scale ◽  
Psammodromus Algirus ◽  
Fragmented Population ◽  
The Impact

Abstract Isolation owing to anthropogenic habitat fragmentation is expected to increase the homozygosity of individuals, which might reduce their fitness as a result of inbreeding depression. Using samples from a fragmented population of the lizard Psammodromus algirus, for which we had data about two correlates of fitness, we genotyped individuals for six microsatellite loci that correctly capture genome-wide individual homozygosity of these lizards (as validated with an independent sample of lizards genotyped for both these microsatellites and > 70 000 single nucleotide polymorphisms). Our data revealed genetic structure at a very small geographical scale, which was compatible with restricted gene flow among populations disconnected in a matrix of inhospitable habitat. Lizards from the same fragment were genetically more related to one another than expected by chance, and individual homozygosity was greater in small than in large fragments. Within fragments, individual homozygosity was negatively associated with adult body size and clutch mass, revealing a link among reduced gene flow, increased homozygosity and lowered fitness that might reduce population viability deterministically. Our results contribute to mounting evidence of the impact of the loss of genetic diversity on fragmented wild populations.

scholarly journals Multi-locus genotyping reveals established endemicity of a geographically distinct Plasmodium vivax population in Mauritania, West Africa

2020 ◽  
Author(s):  
Hampate Ba ◽  
Sarah Auburn ◽  
Christopher G. Jacob ◽  
Sonia Goncalves ◽  
Craig W. Duffy ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Population Structure ◽  
Linkage Disequilibrium ◽  
West Africa ◽  
Plasmodium Vivax ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Genome Wide ◽  
A Genome ◽  
Endemic Transmission

AbstractBackgroundPlasmodium vivax has been recently discovered as a significant cause of malaria in Mauritania, although very rare elsewhere in West Africa. It has not been known if this is a recently introduced or locally remnant parasite population, nor whether the genetic structure reflects epidemic or endemic transmission.Methodology / Principal FindingsTo investigate the P. vivax population genetic structure in Mauritania and compare with populations previously analysed elsewhere, multi-locus genotyping was undertaken on 100 clinical isolates, using a genome-wide panel of 38 single nucleotide polymorphisms (SNPs), plus seven SNPs in drug resistance genes. The Mauritanian P. vivax population is shown to be genetically diverse and divergent from populations elsewhere, indicated consistently by genetic distance matrix analysis, principal components analyses, and fixation indices. Only one isolate had a genotype clearly indicating recent importation, from a southeast Asian source. There was no linkage disequilibrium in the local parasite population, and only a small number of infections appeared to be closely genetically related, indicating that there is ongoing genetic recombination consistent with endemic transmission. The P. vivax diversity in a remote mining town was similar to that in the capital Nouakchott, with no indication of local substructure or of epidemic population structure. Drug resistance alleles were virtually absent in Mauritania, in contrast with P. vivax in other areas of the world.Conclusions / SignificanceThe molecular epidemiology indicates that there is long-standing endemic transmission that will be very challenging to eliminate. The virtual absence of drug resistance alleles suggests that most infections have been untreated, and that this endemic infection has been more neglected in comparison to P. falciparum locally or to P. vivax elsewhere.Author SummaryPlasmodium vivax is a widespread cause of malaria in Mauritania, in contrast to its rarity elsewhere throughout West Africa. To investigate whether the parasite may be recently introduced or epidemic, multi-locus genotyping was performed on 100 Mauritanian P. vivax malaria cases. Analysis of a genome-wide panel of single nucleotide polymorphisms showed the P. vivax population to be genetically diverse and divergent from populations elsewhere, indicating that there has been long-standing endemic transmission. Almost all infections appear to be locally acquired, with the exception of one that was presumably imported with a genotype similar to infections seen in Southeast Asia. The Mauritanian P. vivax population shows no linkage disequilibrium, and very few infections have closely related genotypes, indicating ongoing recombination. The parasite showed no indication of local substructure or epidemic population structure. Drug resistance alleles were virtually absent, suggesting that most infections have been untreated historically. The molecular epidemiology indicates that there has been long-standing endemic transmission of this neglected parasite that requires special attention for control.

scholarly journals Genotypes in relation to phenotypic appearance and exposure to environmental factors in Graves' hyperthyroidism

2012 ◽  
Vol 167 (6) ◽  
pp. 783-792 ◽  
Author(s):  
Xander G Vos ◽  
Erik Endert ◽  
Jan G P Tijssen ◽  
Wilmar M Wiersinga
Keyword(s):  
Linkage Disequilibrium ◽  
Environmental Factors ◽  
Daily Hassles ◽  
First Episode ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Specific Analysis ◽  
Younger Age ◽  
Caucasian Patients ◽  
The Impact

BackgroundGenetic polymorphisms and environmental factors are both involved in the pathogenesis of Graves' disease, but their interaction and effect on Graves' phenotypes have scarcely been investigated.ObjectiveTo test the hypothesis that subjects with susceptibility genotypes develop more severe Graves' hyperthyroidism at a younger age and after less exposure to environmental factors, with attention to gender differences.Study designA prospective observational multicenter study in 205 adult Caucasian patients with untreated first episode of Graves' hyperthyroidism.MethodsEvaluation of genotypes (HLA DRB1*03, DQA1*05, DQB1*02; CTLA4 49A/G, CT60 A/G; PTPN22 C/T) in relation to phenotypes (age, sex, severity (clinical, biochemical, and immunological)) of hyperthyroidism and environmental factors (smoking, stress questionnaires).ResultsG-alleles in CTLA4 single nucleotide polymorphisms were dose-dependently associated with younger age at the time of diagnosis and less exposure to daily hassles. In gender-specific analysis, this association is enhanced in men and attenuated in women. Males (but not females) in HLA linkage disequilibrium had more severe (biochemical and immunological) hyperthyroidism and a tendency to younger age at diagnosis, compared with those not in linkage disequilibrium.ConclusionGraves' hyperthyroidism occurs at a younger age with less exposure to environmental factors in subjects carrying susceptibility genotypes. The impact of genotypes seems to be greater in males than in females.

scholarly journals Absence of Strong Genetic Linkage Disequilibrium between Single Nucleotide Polymorphisms (SNPs) in the Prion Protein Gene (PRNP) and the Prion-Like Protein Gene (PRND) in the Horse, a Prion-Resistant Species

Genes ◽  
2020 ◽  
Vol 11 (5) ◽  
pp. 518
Author(s):  
Sae-Young Won ◽  
Yong-Chan Kim ◽  
Kyoungtag Do ◽  
Byung-Hoon Jeong
Keyword(s):  
Linkage Disequilibrium ◽  
Prion Protein ◽  
Prion Disease ◽  
Protein Gene ◽  
Prion Protein Gene ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Resistant Species ◽  
Disease Resistant ◽  
The Impact

Prion disease is a fatal neurodegenerative disorder caused by a deleterious prion protein (PrPSc). However, prion disease has not been reported in horses during outbreaks of transmissible spongiform encephalopathies (TSEs) in various animals in the UK. In previous studies, single nucleotide polymorphisms (SNPs) in the prion protein gene (PRNP) have been significantly associated with susceptibility to prion disease, and strong linkage disequilibrium (LD) between PRNP and prion-like protein gene (PRND) SNPs has been identified in prion disease-susceptible species. On the other hand, weak LD values have been reported in dogs, a prion disease-resistant species. In this study, we investigated SNPs in the PRND gene and measured the LD values between the PRNP and PRND SNPs and the impact of a nonsynonymous SNP found in the horse PRND gene. To identify SNPs in the PRND gene, we performed direct sequencing of the PRND gene. In addition, to assess whether the weak LD value between the PRNP and PRND SNPs is a characteristic of prion disease-resistant animals, we measured the LD value between the PRNP and PRND SNPs using D’ and r2 values. Furthermore, we evaluated the impact of a nonsynonymous SNP in the Doppel protein with PolyPhen-2, PROVEAN, and PANTHER. We observed two novel SNPs, c.331G > A (A111T) and c.411G > C. The genotype and allele frequencies of the c.331G > A (A111T) and c.411G > C SNPs were significantly different between Jeju, Halla, and Thoroughbred horses. In addition, we found a total of three haplotypes: GG, AG, and GC. The GG haplotype was the most frequently observed in Jeju and Halla horses. Furthermore, the impact of A111T on the Doppel protein was predicted to be benign by PolyPhen-2, PROVEAN, and PANTHER. Interestingly, a weak LD value between the PRNP and PRND SNPs was found in the horse, a prion disease-resistant animal. To the best of our knowledge, these results suggest that a weak LD value could be one feature of prion disease-resistant animals.

scholarly journals The Impact of Homocysteine on the Risk of Hormone-Related Cancers: A Mendelian Randomization Study

2021 ◽  
Vol 8 ◽  
Author(s):  
Qian He ◽  
Ze Yang ◽  
Yandi Sun ◽  
Zihao Qu ◽  
Xueyao Jia ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Single Nucleotide Polymorphisms ◽  
Mendelian Randomization ◽  
Meta Analysis ◽  
Plasma Homocysteine ◽  
European Ancestry ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Genome Wide ◽  
The Impact

Background: Aberrant homocysteine level is associated with metabolic disorders and DNA damage, which may be involved in the carcinogenesis of hormone-related cancers, but clinical results of observational studies are controversial. In this study, we investigated the causal relationships between plasma homocysteine and breast cancer (BRCA), prostate cancer (PrCa), and renal cell carcinoma (RCC) using Mendelian randomization (MR) analyses.Design and Methods: To investigate the putative causal associations between homocysteine and the aforementioned three types of cancers, a two-sample MR study was employed for the study. The primary strategy for summary data analyses was the inverse-variance-weighted (IVW) approach. In our study, the single-nucleotide polymorphisms (SNPs) excluded confounding factors through Linkage Disequilibrium (LD). Phenoscanner tests were the instrumental variants (IVs), homocysteine was the exposure, and BRCA, PrCa, and RCC were the outcomes. Single-nucleotide polymorphisms associated with homocysteine were extracted from a large genome-wide association study (GWAS) meta-analysis of European participants (n = 44,147). Summary Statistics of BRCA were obtained from the latest and largest GWAS meta-analysis comprising of 82 studies from Breast Cancer Association Consortium (BCAC) studies, including women of European ancestry (133,384 cases and 113,789 controls); we obtained summary-level data from the GWAS meta-analysis of PrCa comprising 79,148 cases and 61,106 controls of European ancestry, and the dataset of RCC was a sex-specific GWAS meta-analysis comprising of two kidney cancer genome-wide scans for men (3,227 cases and 4,916 controls) and women (1,992 cases and 3,095 controls) of European ancestry. The MR-Egger and weight median analyses were applied for the pleiotropy test.Results: The results showed null associations between plasma homocysteine levels and overall BRCA (effect = 0.97, 95% CI: 0.90–1.06, P = 0.543), overall PrCa (effect = 1.01, 95% CI: 0.93–1.11, P = 0.774), RCC in men (effect = 0.99, 95% CI: 0.73–1.34, P = 0.929), and RCC in women (effect = 0.89, 95% CI: 0.61–1.31, P = 0.563).Conclusions: We found no putative causal associations between homocysteine and risk of BRCA, PrCa, and RCC.

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