Rare-variant collapsing analyses for complex traits: guidelines and applications

Povysil, Gundula; Petrovski, Slavé; Hostyk, Joseph; Aggarwal, Vimla S.; Allen, Andrew S.; Goldstein, David B.

doi:10.1038/s41576-019-0177-4

Cited by 178 publications

(165 citation statements)

References 100 publications

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“…The main difference between microarrays and RNA-seq is that the latter allows complete sequencing of the transcriptome. Indeed, while microarrays are effective at identifying known genes and transcripts, the information they provide is incomplete as this transcriptomic analysis procedure does not allow the identification of previously unidentified genes [ 110 ]. In contrast, RNA sequencing enables gene expression to be reliably detected and quantified even when genes are expressed at low levels [ 72 ].…”

Section: Transcriptome Profiling Analysis For a Better Understandimentioning

confidence: 99%

Transcriptome Profiling Analyses in Psoriasis: A Dynamic Contribution of Keratinocytes to the Pathogenesis

Rioux

Ridha

Simard

et al. 2020

Genes

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Psoriasis is an immune-mediated inflammatory skin disease with a complex etiology involving environmental and genetic factors. A better insight into related genomic alteration helps design precise therapies leading to better treatment outcome. Gene expression in psoriasis can provide relevant information about the altered expression of mRNA transcripts, thus giving new insights into the disease onset. Techniques for transcriptome analyses, such as microarray and RNA sequencing (RNA-seq), are relevant tools for the discovery of new biomarkers as well as new therapeutic targets. This review summarizes the findings related to the contribution of keratinocytes in the pathogenesis of psoriasis by an in-depth review of studies that have examined psoriatic transcriptomes in the past years. It also provides valuable information on reconstructed 3D psoriatic skin models using cells isolated from psoriatic patients for transcriptomic studies.

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Section: Transcriptome Profiling Analysis For a Better Understandimentioning

confidence: 99%

Transcriptome Profiling Analyses in Psoriasis: A Dynamic Contribution of Keratinocytes to the Pathogenesis

Rioux

Ridha

Simard

et al. 2020

Genes

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“…As results, various statistical analyses have been proposed to maintain or increase statistical power in these different scenarios, which were grouped into four categories: burden tests, variance-component tests, combined tests, and other tests [27]. Details were reviewed by Povysil [28].…”

Section: Contribuɵon To Human Healthmentioning

confidence: 99%

Unique roles of rare variants in the genetics of complex diseases in humans

2020

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Genome-wide association studies have identified >10,000 genetic variants associated with various phenotypes and diseases. Although the majority are common variants, rare variants with >0.1% of minor allele frequency have been investigated by imputation and using disease-specific custom SNP arrays. Rare variants sequencing analysis mainly revealed have played unique roles in the genetics of complex diseases in humans due to their distinctive features, in contrast to common variants. Unique roles are hypothesis-free evidence for gene causality, a precise target of functional analysis for understanding disease mechanisms, a new favorable target for drug development, and a genetic marker with high disease risk for personalized medicine. As whole-genome sequencing continues to identify more rare variants, the roles associated with rare variants will also increase. However, a better estimation of the functional impact of rare variants across whole genome is needed to enhance their contribution to improvements in human health.

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“…Despite the fact that we have recently uncovered the near-complete genome sequences of several organisms, our knowledge of the genes that underlie phenotypic differences within domestic animals remains rudimentary [44]. In particular, for complex quantitative traits, such as growth traits, the genetic basis may be subject to a number of factors including natural selection, inheritance, and evolutionary forces [45,46]. The results from our study suggest the complexity of genetic mechanisms of growth traits in Chinese Simmental beef cattle, as numerous potential genomic regions and candidate genes were associated with growth traits.…”

Section: Potential Genomic Regions and Candidate Genes Reveal The Commentioning

confidence: 99%

Weighted Single-Step Genome-Wide Association Study for Growth Traits in Chinese Simmental Beef Cattle

Zhuang

Yang

et al. 2020

Genes

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Improving the genetic process of growth traits is one of the major goals in the beef cattle industry, as it can increase meat production and reduce the cost of raising animals. Although several quantitative trait loci affecting growth traits in beef cattle have been identified, the genetic architecture of these economically important traits remains elusive. This study aims to map single nucleotide polymorphisms (SNPs) and genes associated with birth weight (BW), yearling weight (YW), average daily gain from birth to yearling (BYADG), and body weight at the age of 18 months (18MW) in a Chinese Simmental beef cattle population using a weighted, single-step, genome-wide association study (wssGWAS). Phenotypic and pedigree data from 6022 animals and genotypes from 744 animals (596,297 SNPs) were used for an association analysis. The results showed that 66 genomic windows explained 1.01-20.15% of the genetic variance for the four examined traits, together with the genes near the top SNP within each window. Furthermore, the identified genomic windows (>1%) explained 50.56%, 57.71%, 61.78%, and 37.82% of the genetic variances for BW, YW, BYADG, and 18MW, respectively. Genes with potential functions in muscle development and regulation of cell growth were highlighted as candidates for growth traits in Simmental cattle (SQOR and TBCB for BW, MYH10 for YW, RLF for BYADG, and ARHGAP31 for 18MW). Moreover, we found 40 SNPs that had not previously been identified as being associated with growth traits in cattle. These findings will further advance our understanding of the genetic basis for growth traits and will be useful for the molecular breeding of BW, YW, BYADG, and 18MW in the context of genomic selection in beef cattle.

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Rare-variant collapsing analyses for complex traits: guidelines and applications

Cited by 178 publications

References 100 publications

Transcriptome Profiling Analyses in Psoriasis: A Dynamic Contribution of Keratinocytes to the Pathogenesis

Transcriptome Profiling Analyses in Psoriasis: A Dynamic Contribution of Keratinocytes to the Pathogenesis

Unique roles of rare variants in the genetics of complex diseases in humans

Weighted Single-Step Genome-Wide Association Study for Growth Traits in Chinese Simmental Beef Cattle

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