Principles and methods for transferring polygenic risk scores across global populations

Nature Reviews Genetics, Год журнала: 2023, Номер 25(1), С. 8 - 25

Опубликована: Авг. 24, 2023

Язык: Английский

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From target discovery to clinical drug development with human genetics

Nature, Год журнала: 2023, Номер 620(7975), С. 737 - 745

Опубликована: Авг. 23, 2023

Язык: Английский

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eXclusionarY: 10 years later, where are the sex chromosomes in GWASs?

The American Journal of Human Genetics, Год журнала: 2023, Номер 110(6), С. 903 - 912

Опубликована: Июнь 1, 2023

10 years ago, a detailed analysis showed that only 33% of genome-wide association study (GWAS) results included the X chromosome. Multiple recommendations were made to combat such exclusion. Here, we re-surveyed research landscape determine whether these earlier had been translated. Unfortunately, among summary statistics reported in 2021 NHGRI-EBI GWAS Catalog, 25% provided for chromosome and 3% Y chromosome, suggesting exclusion phenomenon not persists but has also expanded into an exclusionary problem. Normalizing by physical length average number studies published through November 2022 with genome-wide-significant findings on is ∼1 study/Mb. By contrast, it ranges from ∼6 ∼16 studies/Mb chromosomes 4 19, respectively. Compared autosomal growth rate ∼0.086 studies/Mb/year over last decade, grew at less than one-seventh rate, ∼0.012 studies/Mb/year. Among significant associations noted extreme heterogeneities data reporting results, need clear guidelines. Unsurprisingly, 430 scores sampled PolyGenic Score 0% contained weights sex chromosomal SNPs. To overcome dearth analyses, provide five sets future directions. Finally, until are whole-genome study, instead GWASs, propose would more properly be referred as "AWASs," meaning "autosome-wide scans."

Язык: Английский

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Chloroplast gene expression: Recent advances and perspectives

Plant Communications, Год журнала: 2023, Номер 4(5), С. 100611 - 100611

Опубликована: Май 4, 2023

Chloroplasts evolved from an ancient cyanobacterial endosymbiont more than 1.5 billion years ago. During subsequent coevolution with the nuclear genome, chloroplast genome has remained independent, albeit strongly reduced, its own transcriptional machinery and distinct features, such as chloroplast-specific innovations to gene expression complicated post-transcriptional processing. Light activates of genes via mechanisms that optimize photosynthesis, minimize photodamage, prioritize energy investments. Over past few years, studies have moved stage describing phases explore underlying mechanisms. In this review, we focus on recent advances emerging principles govern in land plants. We discuss PPR protein engineering biotechnological impacts RNA research, new techniques for elucidating molecular expression, some important aspects improving crop yield stress tolerance. also remaining biological mechanistic questions be answered future.

Язык: Английский

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Recent advances in polygenic scores: translation, equitability, methods and FAIR tools

Genome Medicine, Год журнала: 2024, Номер 16(1)

Опубликована: Фев. 19, 2024

Abstract Polygenic scores (PGS) can be used for risk stratification by quantifying individuals’ genetic predisposition to disease, and many potentially clinically useful applications have been proposed. Here, we review the latest potential benefits of PGS in clinic challenges implementation. could augment through combined use with traditional factors (demographics, disease-specific factors, family history, etc.), support diagnostic pathways, predict groups therapeutic benefits, increase efficiency clinical trials. However, there exist maximizing utility PGS, including FAIR (Findable, Accessible, Interoperable, Reusable) standardized sharing genomic data needed develop recalculate equitable performance across populations ancestries, generation robust reproducible calculations, responsible communication interpretation results. We outline how these may overcome analytically more diverse as well highlight sustained community efforts achieve equitable, impactful, healthcare.

Язык: Английский

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Pleiotropy, epistasis and the genetic architecture of quantitative traits

Nature Reviews Genetics, Год журнала: 2024, Номер 25(9), С. 639 - 657

Опубликована: Апрель 2, 2024

Язык: Английский

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Deciphering the impact of genomic variation on function

Nature, Год журнала: 2024, Номер 633(8028), С. 47 - 57

Опубликована: Сен. 4, 2024

Язык: Английский

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Gene–environment interactions in human health

Nature Reviews Genetics, Год журнала: 2024, Номер 25(11), С. 768 - 784

Опубликована: Май 28, 2024

Язык: Английский

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The Polygenic Score Catalog: new functionality and tools to enable FAIR research

medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Май 31, 2024

Abstract Polygenic scores (PGS) have transformed human genetic research and multiple potential clinical applications, including risk stratification for disease prevention prediction of treatment response. Here, we present a series recent enhancements to the PGS Catalog ( www.PGSCatalog.org ), largest findable, accessible, interoperable, reusable (FAIR) repository PGS. These include expansions in data content ancestral diversity as well addition new features. We further Calculator pgsc_calc , https://github.com/PGScatalog/pgsc_calc an open-source, scalable portable pipeline reproducibly calculate that securely democratizes equitable applications by implementing ancestry estimation score normalization using reference data. With & calculator users can now quantify individual’s predisposition hundreds common diseases clinically relevant traits. Taken together, these updates tools facilitate next generation PGS, thus lowering barriers studies necessary identify where may be integrated into practice.

Язык: Английский

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Epigenetics and individuality: from concepts to causality across timescales

Nature Reviews Genetics, Год журнала: 2025, Номер unknown

Опубликована: Янв. 9, 2025

Язык: Английский

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