ORCID Profile
0000-0003-0503-9740
Current Organisations
Hospital for Sick Children
,
University of Toronto
,
Canadian Statistical Sciences Institute (CANSSI)
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Publisher: Public Library of Science (PLoS)
Date: 13-01-2020
Publisher: Proceedings of the National Academy of Sciences
Date: 23-08-2022
Abstract: The use of spoken and written language is a fundamental human capacity. In idual differences in reading- and language-related skills are influenced by genetic variation, with twin-based heritability estimates of 30 to 80% depending on the trait. The genetic architecture is complex, heterogeneous, and multifactorial, but investigations of contributions of single-nucleotide polymorphisms (SNPs) were thus far underpowered. We present a multicohort genome-wide association study (GWAS) of five traits assessed in idually using psychometric measures (word reading, nonword reading, spelling, phoneme awareness, and nonword repetition) in s les of 13,633 to 33,959 participants aged 5 to 26 y. We identified genome-wide significant association with word reading (rs11208009, P = 1.098 × 10 −8 ) at a locus that has not been associated with intelligence or educational attainment. All five reading-/language-related traits showed robust SNP heritability, accounting for 13 to 26% of trait variability. Genomic structural equation modeling revealed a shared genetic factor explaining most of the variation in word/nonword reading, spelling, and phoneme awareness, which only partially overlapped with genetic variation contributing to nonword repetition, intelligence, and educational attainment. A multivariate GWAS of word/nonword reading, spelling, and phoneme awareness maximized power for follow-up investigation. Genetic correlation analysis with neuroimaging traits identified an association with the surface area of the banks of the left superior temporal sulcus, a brain region linked to the processing of spoken and written language. Heritability was enriched for genomic elements regulating gene expression in the fetal brain and in chromosomal regions that are depleted of Neanderthal variants. Together, these results provide avenues for deciphering the biological underpinnings of uniquely human traits.
Publisher: Wiley
Date: 02-12-2020
DOI: 10.1002/ACN3.51255
Publisher: American Society for Clinical Investigation
Date: 15-07-2021
DOI: 10.1172/JCI147834
Publisher: Springer Science and Business Media LLC
Date: 02-05-2023
DOI: 10.1186/S12863-023-01128-3
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. In idual-level data is available to the global research community for health research 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, s ling mechanism, covariate adjustment, and X chromosome analysis. In addition to serving as a rich data source, the ersity of study designs, s le sizes, and research objectives among the participating studies provides unique opportunities for the research community.
Publisher: Elsevier BV
Date: 04-2016
DOI: 10.1038/GIM.2015.79
Publisher: Cold Spring Harbor Laboratory
Date: 10-05-2022
DOI: 10.1101/2022.05.06.22274627
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. In idual-level data is available to the global research community for health research 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, s ling mechanism, covariate adjustment, and X chromosome analysis. In addition to serving as a rich data source, the ersity of study designs, s le sizes, and research objectives among the participating studies provides unique opportunities for the research community.
Publisher: Oxford University Press (OUP)
Date: 31-10-2016
Abstract: Endoplasmic reticulum (ER) stress has been recognized to play an important role in chronic inflammatory diseases such as cystic fibrosis (CF), and targeting ER stress may be useful for alleviating damaging neutrophilic inflammation in CF airways. Cellular models were used in conjunction with data from a recent CF genome-wide association study (GWAS) meta-analysis to determine modulators of ER stress-mediated inflammation. Surprisingly, cells undergoing ER stress during inflammatory stimulation showed reduced interleukin 8 (IL-8) and CXCL1 secretion (P 50% to supernatants from IL-1β-stimulated CF airway epithelial cells (P < .01). The clinical importance of these chemokines was validated by association of CXCL1 and IL8 polymorphisms with changes in lung disease severity in patients with CF (n = 6365 IL8, P = .001 CXCL1, P = .001), confirming that targeting these chemokine pathways could help improve lung disease. We determined that production of these chemokines was partially controlled by ER stress in a signal transducer and activator of transcription 3 (STAT3)-dependent manner, whereby ER stress inhibited STAT3 activation. Our findings support a role for CXCL1 and IL-8 in CF lung disease severity and identify STAT3 as a modulating pathway. Targeting these pathways may help improve health outcomes in CF.
Publisher: Springer Science and Business Media LLC
Date: 02-02-2021
DOI: 10.1038/S41398-020-01121-9
Abstract: Using a novel trait-based measure, we examined genetic variants associated with obsessive-compulsive (OC) traits and tested whether OC traits and obsessive-compulsive disorder (OCD) shared genetic risk. We conducted a genome-wide association analysis (GWAS) of OC traits using the Toronto Obsessive-Compulsive Scale (TOCS) in 5018 unrelated Caucasian children and adolescents from the community (Spit for Science s le). We tested the hypothesis that genetic variants associated with OC traits from the community would be associated with clinical OCD using a meta-analysis of all currently available OCD cases. Shared genetic risk was examined between OC traits and OCD in the respective s les using polygenic risk score and genetic correlation analyses. A locus tagged by rs7856850 in an intron of PTPRD (protein tyrosine phosphatase δ) was significantly associated with OC traits at the genome-wide significance level ( p = 2.48 × 10 −8 ). rs7856850 was also associated with OCD in a meta-analysis of OCD case/control genome-wide datasets ( p = 0.0069). The direction of effect was the same as in the community s le. Polygenic risk scores from OC traits were significantly associated with OCD in case/control datasets and vice versa ( p ’s 0.01). OC traits were highly, but not significantly, genetically correlated with OCD ( r g = 0.71, p = 0.062). We report the first validated genome-wide significant variant for OC traits in PTPRD , downstream of the most significant locus in a previous OCD GWAS. OC traits measured in the community s le shared genetic risk with OCD case/control status. Our results demonstrate the feasibility and power of using trait-based approaches in community s les for genetic discovery.
No related grants have been discovered for Lisa Strug.