1. Long-read sequencing of 3,622 Icelanders provides insight into the role of structural variants in human diseases and other traits
- Author
-
Sverrir T. Sverrisson, Daniel F. Gudbjartsson, Droplaug N Magnusdottir, Ragnar P. Kristjansson, Gisli Masson, Bjarni Torfason, Snaedis Kristmundsdottir, Patrick Sulem, Olof Sigurdardottir, Doruk Beyter, Isleifur Olafsson, Guillaume Holley, Bjarni A Atlason, Aslaug Jonasdottir, Gudmundur I. Eyjolfsson, Helga Ingimundardottir, Hilma Holm, Marteinn T. Hardarson, Asmundur Oddsson, Kari Stefansson, Olafur A. Stefansson, Sigurjon A. Gudjonsson, Hannes P. Eggertsson, Agnar Helgason, Unnur Thorsteinsdottir, Eythor Bjornsson, Svenja Mehringer, Hakon Jonsson, Gunnar K. Pálsson, Adalbjorg Jonasdottir, Bjarni V. Halldorsson, and Olafur T. Magnusson
- Subjects
Genetics ,0303 health sciences ,education.field_of_study ,PCSK9 ,Population ,Biology ,Phenotype ,03 medical and health sciences ,0302 clinical medicine ,Linear relationship ,Allele ,education ,030217 neurology & neurosurgery ,030304 developmental biology - 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.
- Published
- 2021