Genome-wide linkage analysis of cardiovascular disease biomarkers in a large, multigenerational family.

Nolan, Daniel

Kraus, William E

Hauser, Elizabeth

Li, Yi-Ju

Thompson, Dana K

Johnson, Jessica

Chen, Hsiang-Cheng

Nelson, Sarah

Haynes, Carol

Gregory, Simon G

Kraus, Virginia B

Shah, Svati H

Cui, Xinping

United States

2015-11-10T22:40:24Z

2013

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.

http://www.ncbi.nlm.nih.gov/pubmed/23936524

PONE-D-12-30446

1932-6203

https://hdl.handle.net/10161/10873

eng

Public Library of Science (PLoS)

PLoS One

10.1371/journal.pone.0071779

Biomarkers

Cardiovascular Diseases

Family

Female

Genetic Linkage

Genetic Predisposition to Disease

Genome-Wide Association Study

Humans

Lod Score

Male

Middle Aged

Polymorphism, Single Nucleotide

Quantitative Trait Loci

Risk Factors

Genome-wide linkage analysis of cardiovascular disease biomarkers in a large, multigenerational family.

Journal article

Kraus, William E|0000-0003-1930-9684

Hauser, Elizabeth|0000-0003-0367-9189

Li, Yi-Ju|0000-0001-6996-4834

Gregory, Simon G|0000-0002-7805-1743

Kraus, Virginia B|0000-0001-8173-8258

Shah, Svati H|0000-0002-3495-2830

http://www.ncbi.nlm.nih.gov/pubmed/23936524

e71779

8

Basic Science Departments

Biomedical Engineering

Biostatistics & Bioinformatics

Clinical Science Departments

Duke

Duke Cancer Institute

Duke Clinical Research Institute

Duke Molecular Physiology Institute

Institutes and Centers

Medicine

Medicine, Cardiology

Medicine, Rheumatology and Immunology

Molecular Genetics and Microbiology

Neurology

Neurology, MS & Neuroimmunology

Orthopaedics

Pathology

Pratt School of Engineering

School of Medicine

School of Nursing

School of Nursing - Secondary Group

Published online

8