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Sarah A Gagliano Taliun

Sarah A Gagliano Taliun
Université de Montréal & Institut de Cardiologie de Montréal · Médecine & Neurosciences

PhD

About

71
Publications
9,638
Reads
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1,597
Citations
Additional affiliations
July 2020 - present
Université de Montréal
Position
  • Professor (Assistant)
July 2020 - present
Montreal Heart Institute
Position
  • Researcher
July 2016 - June 2020
University of Michigan
Position
  • PostDoc Position
Education
September 2012 - June 2016
University of Toronto
Field of study
  • Medical Science

Publications

Publications (71)
Article
Full-text available
Iron is essential for many biological processes, but iron levels must be tightly regulated to avoid harmful effects of both iron deficiency and overload. Here, we perform genome-wide association studies on four iron-related biomarkers (serum iron, serum ferritin, transferrin saturation, total iron-binding capacity) in the Trøndelag Health Study (HU...
Article
Background: The availability of whole-genome sequencing data in large studies has enabled the assessment of coding and noncoding variants across the allele frequency spectrum for their associations with blood pressure. Methods: We conducted a multiancestry whole-genome sequencing analysis of blood pressure among 51 456 Trans-Omics for Precision...
Preprint
Full-text available
Neurodegenerative diseases overlap neuropathologically and clinically, frequently manifesting with co-pathologies and comorbid symptoms that span multiple domains, including the neuropsychiatric. Genetically, shared risk loci have been identified across neurodegenerative diseases; however, global analyses of genetic correlation (r g ) show minimal...
Preprint
Background Humans are thought to be more susceptible to neurodegeneration than equivalently-aged primates. It is not known whether this vulnerability is specific to anatomically-modern humans or shared with other hominids. The contribution of introgressed Neanderthal DNA to neurodegenerative disorders remains uncertain. It is also unclear how commo...
Article
Background and objectives: Glomerular hematuria has varied causes but can have a genetic basis, including Alport syndrome and IgA nephropathy. Design, setting, participants, & measurements: We used summary statistics to identify genetic variants associated with hematuria in White British UK Biobank participants. Individuals with glomerular hemat...
Article
Full-text available
Rare coding variation has historically provided the most direct connections between gene function and disease pathogenesis. By meta-analysing the whole exomes of 24,248 schizophrenia cases and 97,322 controls, we implicate ultra-rare coding variants (URVs) in 10 genes as conferring substantial risk for schizophrenia (odds ratios of 3–50, P < 2.14 ×...
Preprint
Alzheimer's disease and related dementias (ADRD) are marked by intracellular tau aggregates in the medial-temporal lobe (MTL) and extracellular amyloid aggregates in the default network (DN). Here, we sought to clarify ADRD-related co-dependencies between the MTL's most vulnerable structure, the hippocampus (HC), and the highly associative DN at a...
Preprint
Full-text available
Iron is essential for many biological processes, but iron levels must be tightly regulated to avoid harmful effects of both iron deficiency and overload. Here, we perform genome-wide association studies on four iron related biomarkers (serum iron, serum ferritin, transferrin saturation, total iron binding capacity) in the Trøndelag Health Study (HU...
Preprint
Full-text available
Biobanks housing genetic and phenotypic data for thousands of individuals introduce new opportunities and challenges for genetic association studies. Association testing across many phenotypes increases the multiple-testing burden and correlation between phenotypes makes appropriate multiple-testing correction uncertain. Moreover, analysis includin...
Article
Full-text available
Parkinson’s disease (PD), Parkinson’s disease with dementia (PDD) and dementia with Lewy bodies (DLB) are three clinically, genetically and neuropathologically overlapping neurodegenerative diseases collectively known as the Lewy body diseases (LBDs). A variety of molecular mechanisms have been implicated in PD pathogenesis, but the mechanisms unde...
Article
Full-text available
Circulating cardiac troponin proteins are associated with structural heart disease and predict incident cardiovascular disease in the general population. However, the genetic contribution to cardiac troponin I (cTnI) concentrations and its causal effect on cardiovascular phenotypes is unclear. We combine data from two large population-based studies...
Preprint
Full-text available
Parkinson’s disease (PD), Parkinson’s disease with dementia (PDD) and dementia with Lewy bodies (DLB) are three clinically, genetically and neuropathologically overlapping neurodegenerative diseases collectively known as the Lewy body diseases (LBDs). A variety of molecular mechanisms have been implicated in PD pathogenesis, but the mechanisms unde...
Article
Full-text available
Knowledge of genomic features specific to the human lineage may provide insights into brain-related diseases. We leverage high-depth whole genome sequencing data to generate a combined annotation identifying regions simultaneously depleted for genetic variation (constrained regions) and poorly conserved across primates. We propose that these constr...
Article
Full-text available
The Trans-Omics for Precision Medicine (TOPMed) programme seeks to elucidate the genetic architecture and biology of heart, lung, blood and sleep disorders, with the ultimate goal of improving diagnosis, treatment and prevention of these diseases. The initial phases of the programme focused on whole-genome sequencing of individuals with rich phenot...
Article
Full-text available
Pharmaceutical drugs targeting dyslipidemia and cardiovascular disease (CVD) may increase the risk of fatty liver disease and other metabolic disorders. To identify potential novel CVD drug targets without these adverse effects, we perform genome-wide analyses of participants in the HUNT Study in Norway (n = 69,479) to search for protein-altering v...
Article
Full-text available
Chronic obstructive pulmonary disease (COPD), diagnosed by reduced lung function, is a leading cause of morbidity and mortality. We performed whole genome sequence (WGS) analysis of lung function and COPD in a multi-ethnic sample of 11,497 participants from population- and family-based studies, and 8499 individuals from COPD-enriched studies in the...
Preprint
Full-text available
By meta-analyzing the whole-exomes of 24,248 cases and 97,322 controls, we implicate ultra-rare coding variants (URVs) in ten genes as conferring substantial risk for schizophrenia (odds ratios 3 - 50, P < 2.14 x 10^-6), and 32 genes at a FDR < 5%. These genes have the greatest expression in central nervous system neurons and have diverse molecular...
Preprint
Full-text available
Circulating cardiac troponin proteins are associated with structural heart disease and predict incident cardiovascular disease in the general population. However, the genetic contribution to cardiac troponin I (cTnI) concentrations and its causal effect on cardiovascular phenotypes is unclear. We combine data from the Trondelag Health Study and the...
Article
Full-text available
Neuronal intranuclear inclusion disease (NIID) is a clinically heterogeneous neurodegenerative condition characterized by pathological intranuclear eosinophilic inclusions. A CGG repeat expansion in NOTCH2NLC was recently identified to be associated with NIID in patients of Japanese descent. We screened pathologically confirmed European NIID, cases...
Article
Full-text available
With very large sample sizes, biobanks provide an exciting opportunity to identify genetic components of complex traits. To analyze rare variants, region-based multiple-variant aggregate tests are commonly used to increase power for association tests. However, because of the substantial computational cost, existing region-based tests cannot analyze...
Preprint
Knowledge of genomic features specific to the human lineage may provide insights into brain-related diseases. We leverage high-depth whole genome sequencing data to generate a combined annotation identifying regions simultaneously depleted for genetic variation (constrained regions) and poorly conserved across primates. We propose that these constr...
Conference Paper
Background: Although genome-wide association studies (GWAS) have made important strides in localizing genomic regions associated with blood pressure (BP) phenotypes, the causal mechanisms underlying the vast majority of identified signals remain to be elucidated. Whole genome sequencing (WGS) provides an opportunity for novel genomic discoveries an...
Article
Full-text available
Genome-wide association studies have generated an increasing number of common genetic variants associated with neurological and psychiatric disease risk. An improved understanding of the genetic control of gene expression in human brain is vital considering this is the likely modus operandum for many causal variants. However, human brain sampling c...
Article
Detecting and estimating DNA sample contamination are important steps to ensure high-quality genotype calls and reliable downstream analysis. Existing methods rely on population allele frequency information for accurate estimation of contamination rates. Correctly specifying population allele frequencies for each individual in early stage of sequen...
Article
Full-text available
Parkinson’s disease (PD), with its characteristic loss of nigrostriatal dopaminergic neurons and deposition of α-synuclein in neurons, is often considered a neuronal disorder. However, in recent years substantial evidence has emerged to implicate glial cell types, such as astrocytes and microglia. In this study, we used stratified LD score regressi...
Article
Full-text available
The past decade has seen a surge in the number of disease/trait-associated variants, largely because of the union of studies to share genetic data and the availability of electronic health records from large cohorts for research use. Variant discovery for neurological and neuropsychiatric genome-wide association studies, including schizophrenia, Pa...
Article
Full-text available
Some scientists should reconsider their position on teaching responsibilities, says Sarah A. Gagliano Taliun. Some scientists should reconsider their position on teaching responsibilities, says Sarah A. Gagliano Taliun. Tutor is teaching a group of diverse science students practical skills.
Article
The power of genetic association analyses can be increased by jointly meta‐analyzing multiple correlated phenotypes. Here, we develop a meta‐analysis framework, Meta‐MultiSKAT, that uses summary statistics to test for association between multiple continuous phenotypes and variants in a region of interest. Our approach models the heterogeneity of ef...
Article
Full-text available
Polygenic risk scores (PRS) are designed to serve as single summary measures that are easy to construct, condensing information from a large number of genetic variants associated with a disease. They have been used for stratification and prediction of disease risk. The primary focus of this paper is to demonstrate how we can combine PRS and electro...
Article
Full-text available
Introduction: There is observational evidence that low circulating levels of vitamin B12 are associated with an increased risk of Alzheimer's disease. Methods: We used a two-sample summary-statistics-based Mendelian randomization design to assess the relationship of genetic factors contributing to vitamin B12 with late-onset Alzheimer's disease...
Preprint
Full-text available
Genome-wide association studies (GWAS) have identified thousands of genetic variants associated with various human phenotypes and many of these loci are thought to act at a molecular level by regulating gene expression. Detection of allele specific expression (ASE), namely preferential usage of an allele at a transcribed locus, is an increasingly i...
Preprint
Full-text available
Cardiovascular diseases (CVD), and in particular cerebrovascular and ischemic heart diseases, are leading causes of death globally. Lowering circulating lipids is an important treatment strategy to reduce risk. However, some pharmaceutical mechanisms of reducing CVD may increase risk of fatty liver disease or other metabolic disorders. To identify...
Preprint
Full-text available
The power of genetic association analyses can be increased by jointly meta-analyzing multiple correlated phenotypes. Here, we develop a meta-analysis framework, Meta-MultiSKAT, that uses summary statistics to test for association between multiple continuous phenotypes and variants in a region of interest. Our approach models the heterogeneity of ef...
Preprint
Full-text available
Genome-wide association studies have generated an increasing number of common genetic variants that affect neurological and psychiatric disease risk. Given that many causal variants are likely to operate by regulating gene expression, an improved understanding of the genetic control of gene expression in human brain is vital. However, the difficult...
Preprint
Full-text available
With very large sample sizes, population-based cohorts and biobanks provide an exciting opportunity to identify genetic components of complex traits. To analyze rare variants, gene or region-based multiple variant aggregate tests are commonly used to increase association test power. However, due to the substantial computation cost, existing region-...
Preprint
Full-text available
paragraph The Trans-Omics for Precision Medicine (TOPMed) program seeks to elucidate the genetic architecture and disease biology of heart, lung, blood, and sleep disorders, with the ultimate goal of improving diagnosis, treatment, and prevention. The initial phases of the program focus on whole genome sequencing of individuals with rich phenotypic...
Article
Full-text available
Despite the wealth of genomic and transcriptomic data in Parkinson’s disease (PD), the initial molecular events are unknown. Using LD score regression analysis, we show significant enrichment in PD heritability within regulatory sites for LPS-activated monocytes and that TLR4 expression is highest within human substantia nigra, the most affected br...
Article
Full-text available
In the original publication of this article, the author Magarida Rodrigues was written incorrectly. The correct spelling should have been Margarida Rodrigues. Also the centrifuge speed used to remove fibrillar pellets from the aggregation reaction was written incorrectly as 14.2 rpm and should have been 14,200 rpm. The original article has now been...
Article
Full-text available
It is unclear whether insertions and deletions (indels) are more likely to influence complex traits than abundant single‐nucleotide polymorphisms (SNPs). We sought to understand which category of variation is more likely to impact health. Using the SardiNIA study as an exemplar, we characterized 478,876 common indels and 8,246,244 common SNPs in up...
Preprint
Full-text available
Parkinson's disease (PD), with its characteristic loss of nigrostriatal dopaminergic neurons and deposition of α-synuclein in neurons, is often considered a neuronal disorder. However, in recent years substantial evidence has emerged to implicate glial cell types, such as astrocytes and microglia. In this study, we used stratified LD score regressi...
Article
Full-text available
In genome-wide association studies (GWAS) for thousands of phenotypes in large biobanks, most binary traits have substantially fewer cases than controls. Both of the widely used approaches, the linear mixed model and the recently proposed logistic mixed model, perform poorly; they produce large type I error rates when used to analyze unbalanced cas...
Preprint
Full-text available
Polygenic risk scores (PRS) are designed to serve as a single summary measure, condensing information from a large number of genetic variants associated with a disease. They have been used for stratification and prediction of disease risk. The construction of a PRS often depends on the purpose of the study, the available data/summary estimates, and...
Preprint
Full-text available
In genome-wide association studies (GWAS) for thousands of phenotypes in large biobanks, most binary traits have substantially fewer cases than controls. Both of the widely used approaches, linear mixed model and the recently proposed logistic mixed model, perform poorly – producing large type I error rates – in the analysis of phenotypes with unba...
Article
Full-text available
Improvements in immunosuppression have modified short-term survival of deceased-donor allografts, but not their rate of long-term failure. Mismatches between donor and recipient HLA play an important role in the acute and chronic allogeneic immune response against the graft. Perfect matching at clinically relevant HLA loci does not obviate the need...
Article
A Messiah who must suffer would have been a paradox for the Jewish people of the first century. However, in the Gospel of Matthew, even though the author notes that Jesus Christ is in fact the promised and awaited liberator of the Jewish people, the Messiah must suffer. The author prepares the disciples and his readers to anticipate this paradox by...
Data
Table S2. Overlap among chromatin accessibility annotations for immune cells. The main diagonal shows genome coverage (base pairs) for that cell type. The upper off‐diagonal shows the overlap coverage (base pairs) for that cell‐type pair. The lower off‐diagonal shows the proportion of overlap coverage for that cell‐type pair.
Data
Table S1. Annotation enrichment results. Red cells mark enrichment that survived Bonferroni correction.
Data
Table S3. (A) Ingenuity Pathway Analysis (IPA) results for canonical pathways. Red cells mark enrichment that survived Bonferroni correction. (B) Ingenuity Pathway Analysis (IPA) results for cancer‐related functions. Red cells mark enrichment that survived Bonferroni correction. (C) enrichr KEGG pathway results. Multiplication of the P‐value comput...
Article
Full-text available
Objectives We assessed the current genetic evidence for the involvement of various cell types and tissue types in the etiology of neurodegenerative diseases, especially in relation to the neuroinflammatory hypothesis of neurodegenerative diseases. Methods We obtained large‐scale genome‐wide association study (GWAS) summary statistics from Parkinso...
Preprint
Objectives We assessed the current genetic evidence for the involvement of various cell types and tissue types in the aetiology of neurodegenerative diseases, especially in relation to the neuroinflammatory hypothesis of neurodegenerative diseases. Methods We obtained large-scale genome-wide association study (GWAS) summary statistics from Parkins...
Article
Full-text available
The XXIIIrd World Congress of Psychiatric Genetics meeting, sponsored by the International Society of Psychiatric Genetics, was held in Toronto, ON, Canada, on 16-20 October 2015. Approximately 700 participants attended to discuss the latest state-of-the-art findings in this rapidly advancing and evolving field. The following report was written by...
Article
What makes the molecular study of psychiatric and other neurological conditions particularly challenging compared with other complex traits is the difficulty of accessing the relevant tissue. The Encyclopedia of DNA Elements (ENCODE) project was one of the earliest producers of brain-derived epigenetic functional genomic data, albeit initially from...
Article
Numerous recent studies have suggested that phenotypic effects of DNA sequence variants can be mediated or modulated by their epigenetic marks, such as allele-skewed DNA modification (ASM). Using Affymetrix SNP microarrays, we performed a comprehensive search of ASM effects in human post-mortem brain and sperm samples (total n = 256) from individua...
Article
Full-text available
Although technology has triumphed in facilitating routine genome sequencing, new challenges have been created for the data-analyst. Genome-scale surveys of human variation generate volumes of data that far exceed capabilities for laboratory characterization. By incorporating functional annotations as predictors, statistical learning has been widely...
Article
Full-text available
Background In silico models have recently been created in order to predict which genetic variants are more likely to contribute to the risk of a complex trait given their functional characteristics. However, there has been no comprehensive review as to which type of predictive accuracy measures and data visualization techniques are most useful for...
Article
Suicide claims one million lives worldwide annually, making it a serious public health concern. The risk for suicidal behaviour can be partly explained by genetic factors, as suggested by twin and family studies (reviewed in (Zai et al. 2012)). Recently, genome-wide association studies (GWASs) of suicide attempt on large samples of bipolar disorder...