Prospective study design and data analysis in UK Biobank

Science Translational Medicine, Journal Year: 2024, Volume and Issue: 16(729)

Published: Jan. 10, 2024

Population-based prospective studies, such as UK Biobank, are valuable for generating and testing hypotheses about the potential causes of human disease. We describe how Biobank’s study design, data access policies, approaches to statistical analysis can help minimize error improve interpretability research findings, with implications other population-based studies being established worldwide.

Language: Английский

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Sequencing and characterizing short tandem repeats in the human genome

Nature Reviews Genetics, Journal Year: 2024, Volume and Issue: 25(7), P. 460 - 475

Published: Feb. 16, 2024

Language: Английский

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A deep catalogue of protein-coding variation in 983,578 individuals

Nature, Journal Year: 2024, Volume and Issue: 631(8021), P. 583 - 592

Published: May 20, 2024

Abstract Rare coding variants that substantially affect function provide insights into the biology of a gene 1–3 . However, ascertaining frequency such requires large sample sizes 4–8 Here we present catalogue human protein-coding variation, derived from exome sequencing 983,578 individuals across diverse populations. In total, 23% Regeneron Genetics Center Million Exome (RGC-ME) data come African, East Asian, Indigenous American, Middle Eastern and South Asian ancestry. The includes more than 10.4 million missense 1.1 predicted loss-of-function (pLOF) variants. We identify with rare biallelic pLOF in 4,848 genes, 1,751 which have not been previously reported. From precise quantitative estimates selection against heterozygous loss (LOF), 3,988 LOF-intolerant including 86 were assessed as tolerant 1,153 lack established disease annotation. also define regions depletion at high resolution. Notably, 1,482 genes are depleted despite being Finally, estimate 3% clinically actionable genetic variant, 11,773 reported ClinVar unknown significance likely to be deleterious cryptic splice sites. To facilitate variant interpretation genetics-informed precision medicine, make this resource variation RGC-ME dataset publicly accessible through allele browser.

Language: Английский

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A general and efficient representation of ancestral recombination graphs

Genetics, Journal Year: 2024, Volume and Issue: 228(1)

Published: July 16, 2024

Abstract As a result of recombination, adjacent nucleotides can have different paths genetic inheritance and therefore the genealogical trees for sample DNA sequences vary along genome. The structure capturing details these intricately interwoven is referred to as an ancestral recombination graph (ARG). Classical formalisms focused on mapping coalescence events nodes in ARG. However, this approach out step with some modern developments, which do not represent terms or explicitly infer them. We present simple formalism that defines ARG specific genomes their intervals inheritance, show how it generalizes classical treatments encompasses outputs recent methods. discuss nuances arising from more general structure, argue forms appropriate basis software standard rapidly growing field.

Language: Английский

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Genetic links between ovarian ageing, cancer risk and de novo mutation rates

Nature, Journal Year: 2024, Volume and Issue: 633(8030), P. 608 - 614

Published: Sept. 11, 2024

Language: Английский

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