학술논문
Long-read sequencing of 3,622 Icelanders provides insight into the role of structural variants in human diseases and other traits
Document Type
Report
Author
Source
Nature Genetics. June 2021, Vol. 53 Issue 6, p779, 8 p.
Subject
Language
English
ISSN
1061-4036
Abstract
Author(s): Doruk Beyter [sup.1] , Helga Ingimundardottir [sup.1] , Asmundur Oddsson [sup.1] , Hannes P. Eggertsson [sup.1] [sup.2] , Eythor Bjornsson [sup.1] [sup.3] [sup.4] , Hakon Jonsson [sup.1] , Bjarni [...]
Long-read sequencing (LRS) promises to improve the characterization of structural variants (SVs). We generated LRS data from 3,622 Icelanders and identified a median of 22,636 SVs per individual (a median of 13,353 insertions and 9,474 deletions). We discovered a set of 133,886 reliably genotyped SV alleles and imputed them into 166,281 individuals to explore their effects on diseases and other traits. We discovered an association of a rare deletion in PCSK9 with lower low-density lipoprotein (LDL) cholesterol levels, compared to the population average. We also discovered an association of a multiallelic SV in ACAN with height; we found 11 alleles that differed in the number of a 57-bp-motif repeat and observed a linear relationship between the number of repeats carried and height. These results show that SVs can be accurately characterized at the population scale using LRS data in a genome-wide non-targeted approach and demonstrate how SVs impact phenotypes. Analysis of long-read sequencing data from 3,622 Icelanders identifies a set of high-confidence structural variants and provides insights into their effect on human traits and diseases.
Long-read sequencing (LRS) promises to improve the characterization of structural variants (SVs). We generated LRS data from 3,622 Icelanders and identified a median of 22,636 SVs per individual (a median of 13,353 insertions and 9,474 deletions). We discovered a set of 133,886 reliably genotyped SV alleles and imputed them into 166,281 individuals to explore their effects on diseases and other traits. We discovered an association of a rare deletion in PCSK9 with lower low-density lipoprotein (LDL) cholesterol levels, compared to the population average. We also discovered an association of a multiallelic SV in ACAN with height; we found 11 alleles that differed in the number of a 57-bp-motif repeat and observed a linear relationship between the number of repeats carried and height. These results show that SVs can be accurately characterized at the population scale using LRS data in a genome-wide non-targeted approach and demonstrate how SVs impact phenotypes. Analysis of long-read sequencing data from 3,622 Icelanders identifies a set of high-confidence structural variants and provides insights into their effect on human traits and diseases.