Long-read sequencing (LRS) promises to improve characterization of structural variants (SVs), a major source of genetic diversity. We generated LRS data on 3,622 Icelanders using Oxford Nanopore Technologies, and identified a median of 22,636 SVs per individual (a median of 13,353 insertions and 9,474 deletions), spanning a median of 10 Mb per haploid genome. 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 with a rare (AF = 0.037%) deletion of the first exon of PCSK9. Carriers of this deletion have 0.93 mmol/L (1.31 SD) lower LDL cholesterol levels than the population average (p-value = 7.0•10 −20 ). We also discovered an association with a multi-allelic SV inside a large repeat region, contained within single long reads, in an exon of ACAN. Within this repeat region we found 11 alleles that differ in the number of a 57 bp-motif repeat, and observed a linear relationship (0.016 SD per motif inserted, p = 6.2•10 −18 ) between the number of repeats carried and height. These results show that SVs can be accurately characterized at population scale using long read sequence data in a genome-wide non-targeted approach and demonstrate how SVs impact phenotypes.Human sequence diversity is partially due to structural variants 1 (SVs); genomic rearrangements affecting at least 50 bp of sequence in forms of insertions, deletions, inversions, or translocations. The number of SVs carried by each individual is less than the number of single nucleotide polymorphisms (SNPs) and short (< 50 bp) insertions and deletions (indels), but their greater size makes them more likely to have a functional role 2 , as evident by their disproportionately large impact on diseases and other traits 2,3 .Extensive characterization of three trios sequenced using several technologies 4 and an annotated set based on one sample (HG002) 5 indicate that humans carry 23-31 thousand SVs .

The aim of this investigation was to study the relationship between psychologic status and respiratory health. The study comprised 715 persons aged 22 to 44 who participated in the European Commission Respiratory Health Survey. The study included a structural interview, spirometry, methacholine challenge, peak flow diary, skin prick test, and measurement of eosinophil activity in peripheral blood. The psychologic status was assessed by means of the hospital anxiety and depression (HAD) scale questionnaire. A significant correlation was found between anxiety and depression and the report of asthma-related symptoms, such as attacks of breathlessness after activity and waking with attacks of breathlessness (p < 0.01). However, there was no significant correlation between anxiety or depression and a self-reported diagnosis of asthma or objective asthma-related variables, such as peak flow variability or response to methacholine. When evaluating the combined influence of psychologic factors and objective variables, HAD score correlated independently with reported wheezing (p< 0.05), waking with attacks of breathlessness (p < 0.01), waking with chest tightness, attacks of breathlessness when at rest, and attacks of breathlessness after activity (p < 0.001). We conclude that there is an association between reported respiratory symptoms and psychologic status. However, there was no evidence that patients with diagnosed bronchial asthma had more anxiety and depression than those without asthma. This result indicates that it may be valuable to include psychologic status indicators in respiratory symptom questionnaires.

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