The ChinaMAP reference panel for the accurate genotype imputation in Chinese populations.
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ABSTRACT:
SUBMITTER: Li L
PROVIDER: S-EPMC8648815 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:We describe a reference panel of 64,976 human haplotypes at 39,235,157 SNPs constructed using whole-genome sequence data from 20 studies of predominantly European ancestry. Using this resource leads to accurate genotype imputation at minor allele frequencies as low as 0.1% and a large increase in the number of SNPs tested in association studies, and it can help to discover and refine causal loci. We describe remote server resources that allow researchers to carry out imputation and phasing consistently and efficiently.
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Project description:Pigs not only function as a major meat source worldwide but also are commonly used as an animal model for studying human complex traits. A large haplotype reference panel has been used to facilitate efficient phasing and imputation of relatively sparse genome-wide microarray chips and low-coverage sequencing data. Using the imputed genotypes in the downstream analysis, such as GWASs, TWASs, eQTL mapping and genomic prediction (GS), is beneficial for obtaining novel findings. However, currently, there is still a lack of publicly available and high-quality pig reference panels with large sample sizes and high diversity, which greatly limits the application of genotype imputation in pigs. In response, we built the pig Haplotype Reference Panel (PHARP) database. PHARP provides a reference panel of 2012 pig haplotypes at 34 million SNPs constructed using whole-genome sequence data from more than 49 studies of 71 pig breeds. It also provides Web-based analytical tools that allow researchers to carry out phasing and imputation consistently and efficiently. PHARP is freely accessible at http://alphaindex.zju.edu.cn/PHARP/index.php . We demonstrate its applicability for pig commercial 50 K SNP arrays, by accurately imputing 2.6 billion genotypes at a concordance rate value of 0.971 in 81 Large White pigs (~ 17 × sequencing coverage). We also applied our reference panel to impute the low-density SNP chip into the high-density data for three GWASs and found novel significantly associated SNPs that might be casual variants.
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Project description:BackgroundGenotype imputation is a cost-effective method to generate sequence-level genotypes for a large number of animals. Its application can improve the power of genomic studies, provided that the accuracy of imputation is sufficiently high. The purpose of this study was to develop an optimal strategy for genotype imputation from genotyping array data to sequence level in German warmblood horses, and to investigate the effect of different factors on the accuracy of imputation. Publicly available whole-genome sequence data from 317 horses of 46 breeds was used to conduct the analyses.ResultsDepending on the size and composition of the reference panel, the accuracy of imputation from medium marker density (60K) to sequence level using the software Beagle 5.1 ranged from 0.64 to 0.70 for horse chromosome 3. Generally, imputation accuracy increased as the size of the reference panel increased, but if genetically distant individuals were included in the panel, the accuracy dropped. Imputation was most precise when using a reference panel of multiple but related breeds and the software Beagle 5.1, which outperformed the other two tested computer programs, Impute 5 and Minimac 4. Genome-wide imputation for this scenario resulted in a mean accuracy of 0.66. Stepwise imputation from 60K to 670K markers and subsequently to sequence level did not improve the accuracy of imputation. However, imputation from higher density (670K) was considerably more accurate (about 0.90) than from medium density. Likewise, imputation in genomic regions with a low marker coverage resulted in a reduced accuracy of imputation.ConclusionsThe accuracy of imputation in horses was influenced by the size and composition of the reference panel, the marker density of the genotyping array, and the imputation software. Genotype imputation can be used to extend the limited amount of available sequence-level data from horses in order to boost the power of downstream analyses, such as genome-wide association studies, or the detection of embryonic lethal variants.
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Project description:Many different types of multiparental populations have recently been produced to increase genetic diversity and resolution in QTL mapping. Low-coverage, genotyping-by-sequencing (GBS) technology has become a cost-effective tool in these populations, despite large amounts of missing data in offspring and founders. In this work, we present a general statistical framework for genotype imputation in such experimental crosses from low-coverage GBS data. Generalizing a previously developed hidden Markov model for calculating ancestral origins of offspring DNA, we present an imputation algorithm that does not require parental data and that is applicable to bi- and multiparental populations. Our imputation algorithm allows heterozygosity of parents and offspring as well as error correction in observed genotypes. Further, our approach can combine imputation and genotype calling from sequencing reads, and it also applies to called genotypes from SNP array data. We evaluate our imputation algorithm by simulated and real data sets in four different types of populations: the F2, the advanced intercross recombinant inbred lines, the multiparent advanced generation intercross, and the cross-pollinated population. Because our approach uses marker data and population design information efficiently, the comparisons with previous approaches show that our imputation is accurate at even very low ([Formula: see text]) sequencing depth, in addition to having accurate genotype phasing and error detection.
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Project description:Genome-wide association studies have successfully identified common variants that are associated with complex diseases. However, the majority of genetic variants contributing to disease susceptibility are yet to be discovered. It is now widely believed that multiple rare variants are likely to be associated with complex diseases. Using custom-made chips or next-generation sequencing to uncover the effects of rare variants on the disease can be very expensive in current technology. Consequently, many researchers use the genotype imputation approach to predict the genotypes at these rare variants that are not directly genotyped in the study sample. One important question in genotype imputation is how to choose a reference panel that will produce high imputation accuracy in a population of interest. Using whole genome sequence data from the Genetic Analysis Workshop 18 data set, this report compares genotype imputation accuracy among reference panels representing different degrees of genetic similarity to a study sample of admixed Mexican Americans. Results show that a reference panel that closely matches the ancestry of the study population can increase imputation accuracy, but it can also result in more missing genotype calls. Having a larger-size reference panel can reduce imputation error and missing genotype, but the improvement may be limited. We also find that, for the admixed study sample, the simple selection of a single best-reference panel among HapMap African, European, or Asian population is not appropriate. The composite reference panel combining all available reference data should be used.
| S-EPMC4143631 | biostudies-literature
Project description:Genotype imputation is a process that estimates missing genotypes in terms of the haplotypes and genotypes in a reference panel. It can effectively increase the density of single nucleotide polymorphisms (SNPs), boost the power to identify genetic association and promote the combination of genetic studies. However, there has been a lack of high-quality reference panels for most plants, which greatly hinders the application of genotype imputation. Here, we developed Plant-ImputeDB (http://gong_lab.hzau.edu.cn/Plant_imputeDB/), a comprehensive database with reference panels of 12 plant species for online genotype imputation, SNP and block search and free download. By integrating genotype data and whole-genome resequencing data of plants from various studies and databases, the current Plant-ImputeDB provides high-quality reference panels of 12 plant species, including ∼69.9 million SNPs from 34 244 samples. It also provides an easy-to-use online tool with the option of two popular tools specifically designed for genotype imputation. In addition, Plant-ImputeDB accepts submissions of different types of genomic variations, and provides free and open access to all publicly available data in support of related research worldwide. In general, Plant-ImputeDB may serve as an important resource for plant genotype imputation and greatly facilitate the research on plant genetic research.
| S-EPMC7779032 | biostudies-literature
Project description:There is currently a dearth of accessible whole genome sequencing (WGS) data for individuals residing in the Americas with Sub-Saharan African ancestry. We generated whole genome sequencing data at intermediate (15×) coverage for 2,294 individuals with large amounts of Sub-Saharan African ancestry, predominantly Atlantic African admixed with varying amounts of European and American ancestry. We performed extensive comparisons of variant callers, phasing algorithms, and variant filtration on these data to construct a high quality imputation panel containing data from 2,269 unrelated individuals. With the exception of the TOPMed imputation server (which notably cannot be downloaded), our panel substantially outperformed other available panels when imputing African American individuals. The raw sequencing data, variant calls and imputation panel for this cohort are all freely available via dbGaP and should prove an invaluable resource for further study of admixed African genetics.
| S-EPMC8571350 | biostudies-literature
Project description:Cystic fibrosis (CF) is a severe genetic disorder that can cause multiple comorbidities affecting the lungs, the pancreas, the luminal digestive system and beyond. In our previous genome-wide association studies (GWAS), we genotyped approximately 8,000 CF samples using a mixture of different genotyping platforms. More recently, the Cystic Fibrosis Genome Project (CFGP) performed deep (approximately 30×) whole genome sequencing (WGS) of 5,095 samples to better understand the genetic mechanisms underlying clinical heterogeneity among patients with CF. For mixtures of GWAS array and WGS data, genotype imputation has proven effective in increasing effective sample size. Therefore, we first performed imputation for the approximately 8,000 CF samples with GWAS array genotype using the Trans-Omics for Precision Medicine (TOPMed) freeze 8 reference panel. Our results demonstrate that TOPMed can provide high-quality imputation for patients with CF, boosting genomic coverage from approximately 0.3-4.2 million genotyped markers to approximately 11-43 million well-imputed markers, and significantly improving polygenic risk score (PRS) prediction accuracy. Furthermore, we built a CF-specific CFGP reference panel based on WGS data of patients with CF. We demonstrate that despite having approximately 3% the sample size of TOPMed, our CFGP reference panel can still outperform TOPMed when imputing some CF disease-causing variants, likely owing to allele and haplotype differences between patients with CF and general populations. We anticipate our imputed data for 4,656 samples without WGS data will benefit our subsequent genetic association studies, and the CFGP reference panel built from CF WGS samples will benefit other investigators studying CF.
| S-EPMC8804187 | biostudies-literature
Project description:Genotype imputation is a statistical method for estimating missing genotypes from a denser haplotype reference panel. Existing methods usually performed well on common variants, but they may not be ideal for low-frequency and rare variants. Previous studies showed that the population similarity between study and reference panels is one of the key factors influencing the imputation accuracy. Here, we developed an imputation reference panel reconstruction method (RefRGim) using convolutional neural networks (CNNs), which can generate a study-specified reference panel for each input data based on the genetic similarity of individuals from current study and references. The CNNs were pretrained with single nucleotide polymorphism data from the 1000 Genomes Project. Our evaluations showed that genotype imputation with RefRGim can achieve higher accuracies than original reference panel, especially for low-frequency and rare variants. RefRGim will serve as an efficient reference panel reconstruction method for genotype imputation. RefRGim is freely available via GitHub: https://github.com/shishuo16/RefRGim.
| S-EPMC8575030 | biostudies-literature
Project description:BackgroundGenotype imputation from single-nucleotide polymorphism (SNP) genotype data using a haplotype reference panel consisting of thousands of unrelated individuals from populations of interest can help to identify strongly associated variants in genome-wide association studies. The Tohoku Medical Megabank (TMM) project was established to support the development of precision medicine, together with the whole-genome sequencing of 1070 human genomes from individuals in the Miyagi region (Northeast Japan) and the construction of the 1070 Japanese genome reference panel (1KJPN). Here, we investigated the performance of 1KJPN for genotype imputation of Japanese samples not included in the TMM project and compared it with other population reference panels.ResultsWe found that the 1KJPN population was more similar to other Japanese populations, Nagahama (south-central Japan) and Aki (Shikoku Island), than to East Asian populations in the 1000 Genomes Project other than JPT, suggesting that the large-scale collection (more than 1000) of Japanese genomes from the Miyagi region covered many of the genetic variations of Japanese in mainland Japan. Moreover, 1KJPN outperformed the phase 3 reference panel of the 1000 Genomes Project (1KGPp3) for Japanese samples, and IKJPN showed similar imputation rates for the TMM and other Japanese samples for SNPs with minor allele frequencies (MAFs) higher than 1%.Conclusions1KJPN covered most of the variants found in the samples from areas of the Japanese mainland outside the Miyagi region, implying 1KJPN is representative of the Japanese population's genomes. 1KJPN and successive reference panels are useful genome reference panels for the mainland Japanese population. Importantly, the addition of whole genome sequences not included in the 1KJPN panel improved imputation efficiencies for SNPs with MAFs under 1% for samples from most regions of the Japanese archipelago.
| S-EPMC6057088 | biostudies-literature