Long-read sequencing of 3,622 Icelanders provides insight into the role of structural variants in human diseases and other traits

D Beyter, H Ingimundardottir, A Oddsson… - Nature …, 2021 - nature.com
D Beyter, H Ingimundardottir, A Oddsson, HP Eggertsson, E Bjornsson, H Jonsson
Nature genetics, 2021nature.com
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 …
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.
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