HostSeq : A Canadian Whole Genome Sequencing and Clinical Data Resource

Abstract

HostSeq was launched in April 2020 as a national initiative to integrate whole genome sequencing data from 10,000 Canadians infected with SARS-CoV-2 with clinical information related to their disease experience. The mandate of HostSeq is to support the Canadian and international research communities in their efforts to understand the risk factors for disease and associated health outcomes and support the development of interventions such as vaccines and therapeutics. HostSeq is a collaboration among 13 independent epidemiological studies of SARS-CoV-2 across five provinces in Canada. Aggregated data collected by HostSeq are made available to the public through two data portals: a phenotype portal showing summaries of major variables and their distributions, and a variant search portal enabling queries in a genomic region. Individual-level data is available to the global research community through a Data Access Agreement and Data Access Compliance Office approval. Here we provide an overview of the collective project design along with summary level information for HostSeq. We highlight several statistical considerations for researchers using the HostSeq platform regarding data aggregation, sampling mechanism, covariate adjustment, and X chromosome analysis. In addition to serving as a rich data source, the diversity of study designs, sample sizes, and research objectives among the participating studies provides unique opportunities for the research community.

Establishing association between HLA‐C*04:01 and severe COVID‐19

“…Still, despite the inconsistence or absence of findings reported in those earlier reports, the C*04:01 and COVID-19 severity association has so far been independently recapitulated and reported in six independent, peer-reviewed studies, including within a large (n = 9300) Spanish COVID-19 patient cohort. 18 It has also been re-observed by us independently in a larger and ethnically diverse cohort of Canadian COVID-19 patients (CanCOGeN CGEn HostSeq n = 9460, with 8328 (88.0%) COVID-19 positive patients 23 ) (Figure 2). Although C*04:01 has a restrictive ability to bind only six SARS-CoV-2-derived epitopesone of the worst predicted HLA binder to SARS-CoV-2-derived peptides 17,24,25 -our initial analysis of the Can-COGeN data does not reveal a preferential link between HLA alleles having a limited ability to bind SARS-CoV-2 epitopes when COVID-19, ICU and disease severity status are considered (Figure 2).…”

“…The y axis shows the number of epitopes presented by each allele. 24 The C*04:01 association with severe COVID-19 is significant after Bonferroni correction ( p = 0.0305), along with the low-frequency allele B*53:01 (1.2% vs. 13.2% for C*04:01) in the CanCOGeN patient cohort 23 (n = 61 alleles tested, adjusted FET α < 0.05).…”

Chromosome X-Wide Common Variant Association Study (XWAS) in Autism Spectrum Disorder

“…The MGRB dataset includes most individuals of European ancestry but does not exclude samples from different genetic backgrounds. We also used 9,802 samples from the Host Genome Sequencing Initiative (HostSeq) 45 (ii) remove of potential probe sites using gnomAD 48 , and (iii) relationship control using KING 49 to calculate the kinship coefficient and NAToRA 50 to remove samples with relatedness closer than second degree. After this XWAS cleaning pipeline the autosomal file had 1,075,065 SNPs and 21,089 samples (Figure S1).…”