학술논문
Long-read sequencing of 3,622 Icelanders provides insight into the role of structural variants in human diseases and other traits
Document Type
Original Paper
Author
Beyter, Doruk; Ingimundardottir, Helga; Oddsson, Asmundur; Eggertsson, Hannes P.; Bjornsson, Eythor; Jonsson, Hakon; Atlason, Bjarni A.; Kristmundsdottir, Snaedis; Mehringer, Svenja; Hardarson, Marteinn T.; Gudjonsson, Sigurjon A.; Magnusdottir, Droplaug N.; Jonasdottir, Aslaug; Jonasdottir, Adalbjorg; Kristjansson, Ragnar P.; Sverrisson, Sverrir T.; Holley, Guillaume; Palsson, Gunnar; Stefansson, Olafur A.; Eyjolfsson, Gudmundur; Olafsson, Isleifur; Sigurdardottir, Olof; Torfason, Bjarni; Masson, Gisli; Helgason, Agnar; Thorsteinsdottir, Unnur; Holm, Hilma; Gudbjartsson, Daniel F.; Sulem, Patrick; Magnusson, Olafur T.; Halldorsson, Bjarni V.; Stefansson, Kari
Source
Nature Genetics. 53(6):779-786
Subject
Language
English
ISSN
1061-4036
1546-1718
1546-1718
Abstract
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.
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.