Whole Genome Interpretation for a Family of Five

Corpas, Manuel; Mégy, Karyn; Mistry, Vanisha; Metastasio, Antonio; Lehmann, Edmund

doi:10.3389/fgene.2021.535123

Cited by 3 publications

(3 citation statements)

References 260 publications

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“…We selected this particular family dataset because it has been well studied in the past [13][14][15][16], which affords us a deep knowledge of the family's phenotypes and disease history. Figure 1 shows the family pedigree.…”

Section: Family Datasetmentioning

confidence: 99%

Implementation of individualised polygenic risk score analysis: a test case of a family of four

et al. 2022

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Background Polygenic risk scores (PRS) have been widely applied in research studies, showing how population groups can be stratified into risk categories for many common conditions. As healthcare systems consider applying PRS to keep their populations healthy, little work has been carried out demonstrating their implementation at an individual level. Case presentation We performed a systematic curation of PRS sources from established data repositories, selecting 15 phenotypes, comprising an excess of 37 million SNPs related to cancer, cardiovascular, metabolic and autoimmune diseases. We tested selected phenotypes using whole genome sequencing data for a family of four related individuals. Individual risk scores were given percentile values based upon reference distributions among 1000 Genomes Iberians, Europeans, or all samples. Over 96 billion allele effects were calculated in order to obtain the PRS for each of the individuals analysed here. Conclusions Our results highlight the need for further standardisation in the way PRS are developed and shared, the importance of individual risk assessment rather than the assumption of inherited averages, and the challenges currently posed when translating PRS into risk metrics.

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Section: Family Datasetmentioning

confidence: 99%

Implementation of individualised polygenic risk score analysis: a test case of a family of four

et al. 2022

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“…We selected this particular family dataset because it has been well studied in the past [12][13][14][15], which affords us a deep knowledge of the family's phenotypes and disease history. Figure 1 shows the family pedigree.…”

Section: Family Datasetmentioning

confidence: 99%

Implementation of Individualised Polygenic Risk Score Analysis: A Test Case of a Family of Four

Corpas

Mégy

Metastasio

et al. 2021

Preprint

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Polygenic risk scores (PRS) have been widely applied in research studies, showing how population groups can be stratified into risk categories for many common conditions. As healthcare systems consider applying PRS to keep their populations healthy, little work has been carried out demonstrating their implementation at an individual level. We performed a systematic curation of PRS sources from established data repositories, selecting 27 phenotypes, comprising almost 40 million SNPs related to cancer, cardiovascular, metabolic and autoimmune diseases. We tested selected phenotypes using whole genome sequencing data for a family of four family related individuals, with the 1000 Genomes Project (1000G) Phase III participants as background populations. Over 98 billion allele effects were calculated in order to obtain the PRS for each of the individuals analysed here. PRS calculation for the 1000G cohort of 2,504 participants allows us to develop a methodology for risk inference and general PRS deployment. Our approach for PRS implementation advances the discussion on the adoption of PRS in a preventative healthcare setting.

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“…We expect advances reported in this collection to improve the current implementation at scale of PRS in both private and public health systems. Such research is expected to empower the next generation of genetic testing aiming to make use of PRS as an essential tool for reporting genetic risk [ 13 , 14 ]. We suggest that for PRS to be applied at scale, several important developments are needed to be advanced: (a) to further the collection of diverse data through biobanks, (b) the development of clinical trials making use of PRS and (c) the generation of public/private partnerships with commercial genetic testing companies.…”

mentioning

confidence: 99%

Generalisation of genomic findings and applications of polygenic risk scores

Corpas

Fatumo

2023

BMC Med Genomics

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Polygenic Risk Scores (PRS) (also known as polygenic scores, genetic risk scores or polygenic indexes) capture genetic contributions of a multitude of markers that characterise complex traits. Although their likely application to precision medicine remains to be established, promising advances have included their ability to stratify high risk individuals and targeted screening interventions. Current PRS have been mostly optimised for individuals of Northern European ancestries. If PRS are to become widespread as a tool for healthcare applications, more diverse populations and greater capacity for derived interventions need to be accomplished. In this editorial we aim to attract submissions from the research community that highlight current challenges in development of PRS applications at scale. We also welcome manuscripts that delve into the ethical, social and legal implications that the implementation of PRS may generate.

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Whole Genome Interpretation for a Family of Five

Cited by 3 publications

References 260 publications

Implementation of individualised polygenic risk score analysis: a test case of a family of four

Implementation of individualised polygenic risk score analysis: a test case of a family of four

Implementation of Individualised Polygenic Risk Score Analysis: A Test Case of a Family of Four

Generalisation of genomic findings and applications of polygenic risk scores

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