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Leveraging cell type specific regulatory regions to detect SNPs associated with tissue factor pathway inhibitor plasma levels
ABSTRACT Tissue factor pathway inhibitor (TFPI) regulates the formation of intravascular blood clots, which manifest clinically as ischemic heart disease, ischemic stroke, and venous thromboembolism (VTE). TFPI plasma levels are heritable, but the genetics underlying TFPI plasma level variability are poorly understood. Herein we report the first genome‐wide association scan (GWAS) of TFPI plasma levels, conducted in 251 individuals from five extended French‐Canadian Families ascertained on VTE. To improve discovery, we also applied a hypothesis‐driven (HD) GWAS approach that prioritized single nucleotide polymorphism...
Source: Genetic Epidemiology - April 19, 2017 Category: Epidemiology Authors: Jessica Dennis, Alejandra Medina ‐Rivera, Vinh Truong, Lina Antounians, Nora Zwingerman, Giovana Carrasco, Lisa Strug, Phil Wells, David‐Alexandre Trégouët, Pierre‐Emmanuel Morange, Michael D. Wilson, France Gagnon Tags: RESEARCH ARTICLE Source Type: research

A Fast Multiple‐Kernel Method With Applications to Detect Gene‐Environment Interaction
ABSTRACT Kernel machine (KM) models are a powerful tool for exploring associations between sets of genetic variants and complex traits. Although most KM methods use a single kernel function to assess the marginal effect of a variable set, KM analyses involving multiple kernels have become increasingly popular. Multikernel analysis allows researchers to study more complex problems, such as assessing gene‐gene or gene‐environment interactions, incorporating variance‐component based methods for population substructure into rare‐variant association testing, and assessing the conditional effects of a variable set adjust...
Source: Genetic Epidemiology - July 1, 2015 Category: Epidemiology Authors: Rachel Marceau, Wenbin Lu, Shannon Holloway, Michèle M. Sale, Bradford B. Worrall, Stephen R. Williams, Fang‐Chi Hsu, Jung‐Ying Tzeng Tags: Research Article Source Type: research

Using Phenotypic Heterogeneity to Increase the Power of Genome‐Wide Association Studies: Application to Age at Onset of Ischaemic Stroke Subphenotypes
ABSTRACT Genome‐wide association studies (GWAS) have been successful in identifying common variants related to complex disorders. However, some disorders have proved resistant to this strategy with few associations confirmed, despite evidence from twin and family studies of a genetic component. Sophisticated strategies that account for phenotypic heterogeneity may be required to uncover these genetic contributions. Age at onset is an example of a potential source of this heterogeneity in ischaemic stroke. We explore the contribution of age at onset in the Wellcome Trust Case‐Control Consortium 2 ischaemic stroke study....
Source: Genetic Epidemiology - May 14, 2013 Category: Epidemiology Authors: Matthew Traylor, Steve Bevan, Peter M. Rothwell, Cathie Sudlow, , Martin Dichgans, Hugh S. Markus, Cathryn M. Lewis Tags: Research Article Source Type: research