Genome-wide association studies

Uffelmann, Emil; Huang, Qin Qin; Munung, Nchangwi Syntia; Vries, Jantina de; Okada, Yukinori; Martin, Alicia R.; Martin, Hilary C.; Lappalainen, Tuuli; Posthuma, Daniëlle

doi:10.1038/s43586-021-00056-9

Cited by 1,011 publications

(677 citation statements)

References 296 publications

(279 reference statements)

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“…GWAS is used to identify associations between genotypes and phenotypes by testing for differences in the allele frequency of DNA variants between individuals who differ phenotypically. Technically, the analysis of hundreds of thousands of DNA variants in the genomes of these individuals enables finding those statistically associated with a specific phenotype [ 8 ].…”

Section: Explaining the Heritability Of Appearance Traitsmentioning

confidence: 99%

Predicting Physical Appearance from DNA Data—Towards Genomic Solutions

Pośpiech

Teisseyre

Mielniczuk

et al. 2022

Genes

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The idea of forensic DNA intelligence is to extract from genomic data any information that can help guide the investigation. The clues to the externally visible phenotype are of particular practical importance. The high heritability of the physical phenotype suggests that genetic data can be easily predicted, but this has only become possible with less polygenic traits. The forensic community has developed DNA-based predictive tools by employing a limited number of the most important markers analysed with targeted massive parallel sequencing. The complexity of the genetics of many other appearance phenotypes requires big data coupled with sophisticated machine learning methods to develop accurate genomic predictors. A significant challenge in developing universal genomic predictive methods will be the collection of sufficiently large data sets. These should be created using whole-genome sequencing technology to enable the identification of rare DNA variants implicated in phenotype determination. It is worth noting that the correctness of the forensic sketch generated from the DNA data depends on the inclusion of an age factor. This, however, can be predicted by analysing epigenetic data. An important limitation preventing whole-genome approaches from being commonly used in forensics is the slow progress in the development and implementation of high-throughput, low DNA input sequencing technologies. The example of palaeoanthropology suggests that such methods may possibly be developed in forensics.

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Section: Explaining the Heritability Of Appearance Traitsmentioning

confidence: 99%

Predicting Physical Appearance from DNA Data—Towards Genomic Solutions

Pośpiech

Teisseyre

Mielniczuk

et al. 2022

Genes

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“…With the increasing interest in the study of complex traits, several statistical frameworks and tools have been developed in recent years in order to perform GWAS analyses [19]. In the following subsections, we will explain how these statistical models test for associations between genomic variability and phenotypes.…”

Section: Analytical Framework For Gwasmentioning

confidence: 99%

In Search of Complex Disease Risk through Genome Wide Association Studies

et al. 2021

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The identification and characterisation of genomic changes (variants) that can lead to human diseases is one of the central aims of biomedical research. The generation of catalogues of genetic variants that have an impact on specific diseases is the basis of Personalised Medicine, where diagnoses and treatment protocols are selected according to each patient’s profile. In this context, the study of complex diseases, such as Type 2 diabetes or cardiovascular alterations, is fundamental. However, these diseases result from the combination of multiple genetic and environmental factors, which makes the discovery of causal variants particularly challenging at a statistical and computational level. Genome-Wide Association Studies (GWAS), which are based on the statistical analysis of genetic variant frequencies across non-diseased and diseased individuals, have been successful in finding genetic variants that are associated to specific diseases or phenotypic traits. But GWAS methodology is limited when considering important genetic aspects of the disease and has not yet resulted in meaningful translation to clinical practice. This review presents an outlook on the study of the link between genetics and complex phenotypes. We first present an overview of the past and current statistical methods used in the field. Next, we discuss current practices and their main limitations. Finally, we describe the open challenges that remain and that might benefit greatly from further mathematical developments.

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“…Today, we endeavor to establish a complete picture of human systems biology. To accomplish this, it is important to gather multiple layers of research: quantitative behavioral analysis in humans and genome-wide analysis of associated genes (Seshadri et al 2010;Jansen et al 2019;Uffelmann et al 2021). This is in addition to high-throughput model animal phenotyping studies as well as further analysis of key regulators of the target systems at a molecular level in vitro (Fig.…”

Section: From Correlation To Causalitymentioning

confidence: 99%

Towards organism-level systems biology by next-generation genetics and whole-organ cell profiling

2021

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The system-level identification and analysis of molecular and cellular networks in mammals can be accelerated by "nextgeneration" genetics, which is defined as genetics that can achieve desired genetic makeup in a single generation without any animal crossing. We recently established a highly efficient procedure for producing knock-out (KO) mice using the "Triple-CRISPR" method, which targets a single gene by triple gRNAs in the CRISPR/Cas9 system. This procedure achieved an almost perfect KO efficiency (96-100%). We also established a highly efficient procedure, the "ES-mouse" method, for producing knock-in (KI) mice within a single generation. In this method, ES cells were treated with three inhibitors to keep their potency and then injected into 8-cell-stage embryos. These procedures dramatically shortened the time required to produce KO or KI mice from years down to about 3 months. The produced KO and KI mice can also be systematically profiled at a single-cell resolution by the "whole-organ cell profiling," which was realized by tissue-clearing methods, such as CUBIC, and an advanced light-sheet microscopy. The review describes the establishment and application of these technologies above in analyzing the three states (NREM sleep, REM sleep, and awake) of mammalian brains. It also discusses the role of calcium and muscarinic receptors in these states as well as the current challenges and future opportunities in the next-generation mammalian genetics and whole-organ cell profiling for organism-level systems biology.

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Genome-wide association studies

Abstract: The non-independent association of two alleles in a population.

Cited by 1,011 publications

References 296 publications

Predicting Physical Appearance from DNA Data—Towards Genomic Solutions

Predicting Physical Appearance from DNA Data—Towards Genomic Solutions

In Search of Complex Disease Risk through Genome Wide Association Studies

Towards organism-level systems biology by next-generation genetics and whole-organ cell profiling

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