Multiethnic catalog of structural variants and their translational impact for disease phenotypes across 19,652 genomes
Multiethnic catalog of structural variants and their translational impact for disease phenotypes across 19,652 genomes
Abstract Genome sequencing at population scale provides unprecedented access to the genetic foundations of human phenotypic diversity, but genotype-phenotype association analyses limited to small variants have failed to comprehensively characterize the genetic architecture of human health and disease because they ignore structural variants (SVs) known to contribute to phenotypic variation and pathogenic conditions1–3. Here we demonstrate the significance of SVs when assessing genotype-phenotype associations and the importance of ethnic diversity in study design by analyzing SVs across 19,652 individuals and the translational impact on 4,156 aptamerbased proteomic measurements across 4,021 multi-ethnic samples. The majority of 304,533 SVs detected are rare, although we identified 2,336 protein-coding genes impacted by common SVs.We identified 64 significant SV-protein associations that comprise 36 cis- and 28 trans-acting relationships, and 21 distinct SV regions overlapped with genome-wide association study loci. These findings represent a more comprehensive mapping of regulatory and translational endophenotypes underlying health and disease.
Qi Qibin、Sedlazeck Fritz J.、Menon Vipin、BCM HGSC Sequencing Lab、Hu Jianhong、Boerwinkle Eric、Metcalf Ginger A.、Coresh Josef、Zarate Samantha、Chen Han、Jun Goo、Muzny Donna M.、Traynelis Joshua L.、Doddapaneni Harsha、Kaplan Robert C.、Tin Adrienne、Yu Bing、Gibbs Richard A.、Krasheninina Olga、Mansfield Adam J.、Salerno William J.
Department of Epidemiology and Population Health, Albert Einstein College of MedicineHuman Genome Sequencing Center, Baylor College of MedicineHuman Genome Sequencing Center, Baylor College of MedicineHuman Genome Sequencing Center, Baylor College of MedicineHuman Genome Sequencing Center, Baylor College of Medicine||School of Public Health, University of Texas Health Science Center at HoustonHuman Genome Sequencing Center, Baylor College of MedicineBloomberg School of Public Health, Johns Hopkins UniversityDNAnexusSchool of Public Health, University of Texas Health Science Center at HoustonSchool of Public Health, University of Texas Health Science Center at HoustonHuman Genome Sequencing Center, Baylor College of MedicineHuman Genome Sequencing Center, Baylor College of MedicineHuman Genome Sequencing Center, Baylor College of MedicineDepartment of Epidemiology and Population Health, Albert Einstein College of Medicine||Division of Public Health Sciences, Fred Hutchinson Cancer Research CenterBloomberg School of Public Health, Johns Hopkins UniversitySchool of Public Health, University of Texas Health Science Center at HoustonHuman Genome Sequencing Center, Baylor College of MedicineHuman Genome Sequencing Center, Baylor College of MedicineHuman Genome Sequencing Center, Baylor College of MedicineHuman Genome Sequencing Center, Baylor College of Medicine
医学研究方法基础医学生物科学研究方法、生物科学研究技术
Qi Qibin,Sedlazeck Fritz J.,Menon Vipin,BCM HGSC Sequencing Lab,Hu Jianhong,Boerwinkle Eric,Metcalf Ginger A.,Coresh Josef,Zarate Samantha,Chen Han,Jun Goo,Muzny Donna M.,Traynelis Joshua L.,Doddapaneni Harsha,Kaplan Robert C.,Tin Adrienne,Yu Bing,Gibbs Richard A.,Krasheninina Olga,Mansfield Adam J.,Salerno William J..Multiethnic catalog of structural variants and their translational impact for disease phenotypes across 19,652 genomes[EB/OL].(2025-03-28)[2025-06-10].https://www.biorxiv.org/content/10.1101/2020.05.02.074096.点此复制
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