Genome-wide linkage analysis of cardiovascular disease biomarkers in a large, multigenerational family.
Repository Usage Stats
Given the importance of cardiovascular disease (CVD) to public health and the demonstrated heritability of both disease status and its related risk factors, identifying the genetic variation underlying these susceptibilities is a critical step in understanding the pathogenesis of CVD and informing prevention and treatment strategies. Although one can look for genetic variation underlying susceptibility to CVD per se, it can be difficult to define the disease phenotype for such a qualitative analysis and CVD itself represents a convergence of diverse etiologic pathways. Alternatively, one can study the genetics of intermediate traits that are known risk factors for CVD, which can be measured quantitatively. Using the latter strategy, we have measured 21 cardiovascular-related biomarkers in an extended multigenerational pedigree, the CARRIAGE family (Carolinas Region Interaction of Aging, Genes, and Environment). These biomarkers belong to inflammatory and immune, connective tissue, lipid, and hemostasis pathways. Of these, 18 met our quality control standards. Using the pedigree and biomarker data, we have estimated the broad sense heritability (H2) of each biomarker (ranging from 0.09-0.56). A genome-wide panel of 6,015 SNPs was used subsequently to map these biomarkers as quantitative traits. Four showed noteworthy evidence for linkage in multipoint analysis (LOD score ≥ 2.6): paraoxonase (chromosome 8p11, 21), the chemokine RANTES (22q13.33), matrix metalloproteinase 3 (MMP3, 17p13.3), and granulocyte colony stimulating factor (GCSF, 8q22.1). Identifying the causal variation underlying each linkage score will help to unravel the genetic architecture of these quantitative traits and, by extension, the genetic architecture of cardiovascular risk.
Genetic Predisposition to Disease
Genome-Wide Association Study
Polymorphism, Single Nucleotide
Quantitative Trait Loci
Published Version (Please cite this version)10.1371/journal.pone.0071779
Publication InfoChen, HC; Gregory, Simon Gray; Hauser, Elizabeth Rebecca; Haynes, Carol; Johnson, J; Kraus, Virginia Byers; ... Thompson, DK (2013). Genome-wide linkage analysis of cardiovascular disease biomarkers in a large, multigenerational family. PLoS One, 8(8). pp. e71779. 10.1371/journal.pone.0071779. Retrieved from http://hdl.handle.net/10161/10873.
This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.
More InfoShow full item record
Professor in Neurology
My principal area of research involves elucidating the molecular mechanisms underlying multi-factorial diseases. My lab is primarily interested identifying the complex genetic factors that give rise to multiple sclerosis, autism and cardiovascular disease. We are using targeted approaches to identify differential methylation of the oxytocin receptor gene (OXTR) in individuals with autism, and applying these data to an NICHD funded ACE award, SOARS-B, to assess long term use of oxytocin nasal spr
Professor of Biostatistics and Bioinformatics
My research interests are focused on developing and applying statistical methods to search for genes causing common human diseases. Recent work has been in the development of statistical methods for genetic studies and in identifying optimal study designs for genetic studies of complex traits. As application of these methods to specific diseases has progressed it has become apparent that etiologic and genetic heterogeneity is a major stumbling block in the research for genes for common diseases.
Professor of Medicine
My special area of expertise is as a clinician scientist investigating osteoarthritis. Osteoarthritis is the most common form of joint disease in man and its incidence increases with age. It is a problem of increasing concern to the medical community due to the increasing longevity of the population. Trained as a molecular biologist and a Rheumatologist, I endeavor to study this disease from bedside to bench. The work in this laboratory focuses on osteoarthritis and deals w
Richard and Pat Johnson University Professor
My training, expertise and research interests range from human integrative physiology and genetics to animal exercise models to cell culture models of skeletal muscle adaptation to mechanical stretch. I am trained clinically as an internist and preventive cardiologist, with particular expertise in preventive cardiology and cardiac rehabilitation. My research training spans molecular biology and cell culture, molecular genetics, and integrative human exercise physiology and metabolism. I pr
Alphabetical list of authors with Scholars@Duke profiles.